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Sample records for defined brain regions

  1. Normalized regional brain atrophy measurements in multiple sclerosis

    International Nuclear Information System (INIS)

    Zivadinov, Robert; Locatelli, Laura; Stival, Barbara; Bratina, Alessio; Nasuelli, Davide; Zorzon, Marino; Grop, Attilio; Brnabic-Razmilic, Ozana

    2003-01-01

    There is still a controversy regarding the best regional brain atrophy measurements in multiple sclerosis (MS) studies. The aim of this study was to establish whether, in a cross-sectional study, the normalized measurements of regional brain atrophy correlate better with the MRI-defined regional brain lesions than the absolute measurements of regional brain atrophy. We assessed 45 patients with clinically definite relapsing-remitting (RR) MS (median disease duration 12 years), and measured T1-lesion load (LL) and T2-LL of frontal lobes and pons, using a reproducible semi-automated technique. The regional brain parenchymal volume (RBPV) of frontal lobes and pons was obtained by use of a computerized interactive program, which incorporates semi-automated and automated segmentation processes. A normalized measurement, the regional brain parenchymal fraction (RBPF), was calculated as the ratio of RBPV to the total volume of the parenchyma and the cerebrospinal fluid (CSF) in the frontal lobes and in the region of the pons. The total regional brain volume fraction (TRBVF) was obtained after we had corrected for the total volume of the parenchyma and the CSF in the frontal lobes and in the region of the pons for the total intracranial volume. The mean coefficient of variation (CV) for RBPF of the pons was 1% for intra-observer reproducibility and 1.4% for inter-observer reproducibility. Generally, the normalized measurements of regional brain atrophy correlated with regional brain volumes and disability better than did the absolute measurements. RBPF and TRBVF correlated with T2-LL of the pons (r=-0.37, P=0.011, and r= -0.40, P=0.0005 respectively) and with T1-LL of the pons (r=-0.27, P=0.046, and r=-0.31, P=0.04, respectively), whereas RBPV did not (r=-0.18, P = NS). T1-LL of the frontal lobes was related to RBPF (r=-0.32, P=0.033) and TRBVF (r=-0.29, P=0.05), but not to RBPV (R=-0.27, P= NS). There was only a trend of correlation between T2-LL of the frontal lobes and

  2. Defining nodes in complex brain networks

    Directory of Open Access Journals (Sweden)

    Matthew Lawrence Stanley

    2013-11-01

    Full Text Available Network science holds great promise for expanding our understanding of the human brain in health, disease, development, and aging. Network analyses are quickly becoming the method of choice for analyzing functional MRI data. However, many technical issues have yet to be confronted in order to optimize results. One particular issue that remains controversial in functional brain network analyses is the definition of a network node. In functional brain networks a node represents some predefined collection of brain tissue, and an edge measures the functional connectivity between pairs of nodes. The characteristics of a node, chosen by the researcher, vary considerably in the literature. This manuscript reviews the current state of the art based on published manuscripts and highlights the strengths and weaknesses of three main methods for defining nodes. Voxel-wise networks are constructed by assigning a node to each, equally sized brain area (voxel. The fMRI time-series recorded from each voxel is then used to create the functional network. Anatomical methods utilize atlases to define the nodes based on brain structure. The fMRI time-series from all voxels within the anatomical area are averaged and subsequently used to generate the network. Functional activation methods rely on data from traditional fMRI activation studies, often from databases, to identify network nodes. Such methods identify the peaks or centers of mass from activation maps to determine the location of the nodes. Small (~10-20 millimeter diameter spheres located at the coordinates of the activation foci are then applied to the data being used in the network analysis. The fMRI time-series from all voxels in the sphere are then averaged, and the resultant time series is used to generate the network. We attempt to clarify the discussion and move the study of complex brain networks forward. While the correct method to be used remains an open, possibly unsolvable question that

  3. Regional growth and atlasing of the developing human brain.

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    Makropoulos, Antonios; Aljabar, Paul; Wright, Robert; Hüning, Britta; Merchant, Nazakat; Arichi, Tomoki; Tusor, Nora; Hajnal, Joseph V; Edwards, A David; Counsell, Serena J; Rueckert, Daniel

    2016-01-15

    Detailed morphometric analysis of the neonatal brain is required to characterise brain development and define neuroimaging biomarkers related to impaired brain growth. Accurate automatic segmentation of neonatal brain MRI is a prerequisite to analyse large datasets. We have previously presented an accurate and robust automatic segmentation technique for parcellating the neonatal brain into multiple cortical and subcortical regions. In this study, we further extend our segmentation method to detect cortical sulci and provide a detailed delineation of the cortical ribbon. These detailed segmentations are used to build a 4-dimensional spatio-temporal structural atlas of the brain for 82 cortical and subcortical structures throughout this developmental period. We employ the algorithm to segment an extensive database of 420 MR images of the developing brain, from 27 to 45weeks post-menstrual age at imaging. Regional volumetric and cortical surface measurements are derived and used to investigate brain growth and development during this critical period and to assess the impact of immaturity at birth. Whole brain volume, the absolute volume of all structures studied, cortical curvature and cortical surface area increased with increasing age at scan. Relative volumes of cortical grey matter, cerebellum and cerebrospinal fluid increased with age at scan, while relative volumes of white matter, ventricles, brainstem and basal ganglia and thalami decreased. Preterm infants at term had smaller whole brain volumes, reduced regional white matter and cortical and subcortical grey matter volumes, and reduced cortical surface area compared with term born controls, while ventricular volume was greater in the preterm group. Increasing prematurity at birth was associated with a reduction in total and regional white matter, cortical and subcortical grey matter volume, an increase in ventricular volume, and reduced cortical surface area. Copyright © 2015 The Authors. Published by

  4. Evolution of brain region volumes during artificial selection for relative brain size.

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    Kotrschal, Alexander; Zeng, Hong-Li; van der Bijl, Wouter; Öhman-Mägi, Caroline; Kotrschal, Kurt; Pelckmans, Kristiaan; Kolm, Niclas

    2017-12-01

    The vertebrate brain shows an extremely conserved layout across taxa. Still, the relative sizes of separate brain regions vary markedly between species. One interesting pattern is that larger brains seem associated with increased relative sizes only of certain brain regions, for instance telencephalon and cerebellum. Till now, the evolutionary association between separate brain regions and overall brain size is based on comparative evidence and remains experimentally untested. Here, we test the evolutionary response of brain regions to directional selection on brain size in guppies (Poecilia reticulata) selected for large and small relative brain size. In these animals, artificial selection led to a fast response in relative brain size, while body size remained unchanged. We use microcomputer tomography to investigate how the volumes of 11 main brain regions respond to selection for larger versus smaller brains. We found no differences in relative brain region volumes between large- and small-brained animals and only minor sex-specific variation. Also, selection did not change allometric scaling between brain and brain region sizes. Our results suggest that brain regions respond similarly to strong directional selection on relative brain size, which indicates that brain anatomy variation in contemporary species most likely stem from direct selection on key regions. © 2017 The Author(s). Evolution © 2017 The Society for the Study of Evolution.

  5. Radiotherapy for brain metastases: defining palliative response

    International Nuclear Information System (INIS)

    Bezjak, Andrea; Adam, Janice; Panzarella, Tony; Levin, Wilfred; Barton, Rachael; Kirkbride, Peter; McLean, Michael; Mason, Warren; Wong, Chong Shun; Laperriere, Normand

    2001-01-01

    Background and purpose: Most patients with brain metastases are treated with palliative whole brain radiotherapy (WBRT). There is no established definition of palliative response. The aim of this study was to develop and test clinically useful criteria for response following palliative WBRT. Materials and methods: A prospective study was conducted of patients with symptomatic brain metastases treated with WBRT (20 Gy/5 fractions) and standardised steroid tapering. Assessments included observer rating of neurological symptoms, patient-completed symptom checklist and performance status (PS). Response criteria were operationally defined based on a combination of neurological symptoms, PS and steroid dose. Results: Seventy-five patients were accrued. At 1 month, presenting neurological symptoms were improved in 14 patients, stable in 17, and worse in 21; 23 patients were not assessed, mainly due to death or frailty. Using response criteria defined a priori, 15% (95% CI 7-23%) of patients were classified as having a response to RT, 25% no response, and 29% progression; 27% were deceased at or soon after 1 month. A revised set of criteria was tested, with less emphasis on complete tapering of steroids: they increased the proportion of patients responding to 39% (95% CI 27-50%) but didn't change the large proportion who did not benefit (44%). Conclusions: Clinical response to RT of patients with brain metastases is multifactorial, comprising symptoms, PS and other factors. Assessment of degree of palliation depend on the exact definition used. More research is needed in this important area, to help validate criteria for assessing palliation after WBRT

  6. Cortical region of interest definition on SPECT brain images using X-ray CT registration

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    Tzourio, N.; Sutton, D. (Commissariat a l' Energie Atomique, Orsay (France). Service Hospitalier Frederic Joliot); Joliot, M. (Commissariat a l' Energie Atomique, Orsay (France). Service Hospitalier Frederic Joliot INSERM, Orsay (France)); Mazoyer, B.M. (Commissariat a l' Energie Atomique, Orsay (France). Service Hospitalier Frederic Joliot Antenne d' Information Medicale, C.H.U. Bichat, Paris (France)); Charlot, V. (Hopital Louis Mourier, Colombes (France). Service de Psychiatrie); Salamon, G. (CHU La Timone, Marseille (France). Service de Neuroradiologie)

    1992-11-01

    We present a method for brain single photon emission computed tomography (SPECT) analysis based on individual registration of anatomical (CT) and functional ([sup 133]Xe regional cerebral blood flow) images and on the definition of three-dimensional functional regions of interest. Registration of CT and SPECT is performed through adjustment of CT-defined cortex limits to the SPECT image. Regions are defined by sectioning a cortical ribbon on the CT images, copied over the SPECT images and pooled through slices to give 3D cortical regions of interest. The proposed method shows good intra- and interobserver reproducibility (regional intraclass correlation coefficient [approx equal]0.98), and good accuracy in terms of repositioning ([approx equal]3.5 mm) as compared to the SPECT image resolution (14 mm). The method should be particularly useful for analysing SPECT studies when variations in brain anatomy (normal or abnormal) must be accounted for. (orig.).

  7. Brain region specific mitophagy capacity could contribute to selective neuronal vulnerability in Parkinson's disease

    Directory of Open Access Journals (Sweden)

    Zabel Claus

    2011-09-01

    Full Text Available Abstract Parkinson's disease (PD is histologically well defined by its characteristic degeneration of dopaminergic neurons in the substantia nigra pars compacta. Remarkably, divergent PD-related mutations can generate comparable brain region specific pathologies. This indicates that some intrinsic region-specificity respecting differential neuron vulnerability exists, which codetermines the disease progression. To gain insight into the pathomechanism of PD, we investigated protein expression and protein oxidation patterns of three different brain regions in a PD mouse model, the PINK1 knockout mice (PINK1-KO, in comparison to wild type control mice. The dysfunction of PINK1 presumably affects mitochondrial turnover by disturbing mitochondrial autophagic pathways. The three brain regions investigated are the midbrain, which is the location of substantia nigra; striatum, the major efferent region of substantia nigra; and cerebral cortex, which is more distal to PD pathology. In all three regions, mitochondrial proteins responsible for energy metabolism and membrane potential were significantly altered in the PINK1-KO mice, but with very different region specific accents in terms of up/down-regulations. This suggests that disturbed mitophagy presumably induced by PINK1 knockout has heterogeneous impacts on different brain regions. Specifically, the midbrain tissue seems to be most severely hit by defective mitochondrial turnover, whereas cortex and striatum could compensate for mitophagy nonfunction by feedback stimulation of other catabolic programs. In addition, cerebral cortex tissues showed the mildest level of protein oxidation in both PINK1-KO and wild type mice, indicating either a better oxidative protection or less reactive oxygen species (ROS pressure in this brain region. Ultra-structural histological examination in normal mouse brain revealed higher incidences of mitophagy vacuoles in cerebral cortex than in striatum and substantia

  8. Region-specific protein misfolding cyclic amplification reproduces brain tropism of prion strains.

    Science.gov (United States)

    Privat, Nicolas; Levavasseur, Etienne; Yildirim, Serfildan; Hannaoui, Samia; Brandel, Jean-Philippe; Laplanche, Jean-Louis; Béringue, Vincent; Seilhean, Danielle; Haïk, Stéphane

    2017-10-06

    Human prion diseases such as Creutzfeldt-Jakob disease are transmissible brain proteinopathies, characterized by the accumulation of a misfolded isoform of the host cellular prion protein (PrP) in the brain. According to the prion model, prions are defined as proteinaceous infectious particles composed solely of this abnormal isoform of PrP (PrP Sc ). Even in the absence of genetic material, various prion strains can be propagated in experimental models. They can be distinguished by the pattern of disease they produce and especially by the localization of PrP Sc deposits within the brain and the spongiform lesions they induce. The mechanisms involved in this strain-specific targeting of distinct brain regions still are a fundamental, unresolved question in prion research. To address this question, we exploited a prion conversion in vitro assay, protein misfolding cyclic amplification (PMCA), by using experimental scrapie and human prion strains as seeds and specific brain regions from mice and humans as substrates. We show here that region-specific PMCA in part reproduces the specific brain targeting observed in experimental, acquired, and sporadic Creutzfeldt-Jakob diseases. Furthermore, we provide evidence that, in addition to cellular prion protein, other region- and species-specific molecular factors influence the strain-dependent prion conversion process. This important step toward understanding prion strain propagation in the human brain may impact research on the molecular factors involved in protein misfolding and the development of ultrasensitive methods for diagnosing prion disease. © 2017 by The American Society for Biochemistry and Molecular Biology, Inc.

  9. Common DNA methylation alterations in multiple brain regions in autism.

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    Ladd-Acosta, C; Hansen, K D; Briem, E; Fallin, M D; Kaufmann, W E; Feinberg, A P

    2014-08-01

    Autism spectrum disorders (ASD) are increasingly common neurodevelopmental disorders defined clinically by a triad of features including impairment in social interaction, impairment in communication in social situations and restricted and repetitive patterns of behavior and interests, with considerable phenotypic heterogeneity among individuals. Although heritability estimates for ASD are high, conventional genetic-based efforts to identify genes involved in ASD have yielded only few reproducible candidate genes that account for only a small proportion of ASDs. There is mounting evidence to suggest environmental and epigenetic factors play a stronger role in the etiology of ASD than previously thought. To begin to understand the contribution of epigenetics to ASD, we have examined DNA methylation (DNAm) in a pilot study of postmortem brain tissue from 19 autism cases and 21 unrelated controls, among three brain regions including dorsolateral prefrontal cortex, temporal cortex and cerebellum. We measured over 485,000 CpG loci across a diverse set of functionally relevant genomic regions using the Infinium HumanMethylation450 BeadChip and identified four genome-wide significant differentially methylated regions (DMRs) using a bump hunting approach and a permutation-based multiple testing correction method. We replicated 3/4 DMRs identified in our genome-wide screen in a different set of samples and across different brain regions. The DMRs identified in this study represent suggestive evidence for commonly altered methylation sites in ASD and provide several promising new candidate genes.

  10. Regional brain morphometry predicts memory rehabilitation outcome after traumatic brain injury

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    Gary E Strangman

    2010-10-01

    Full Text Available Cognitive deficits following traumatic brain injury (TBI commonly include difficulties with memory, attention, and executive dysfunction. These deficits are amenable to cognitive rehabilitation, but optimally selecting rehabilitation programs for individual patients remains a challenge. Recent methods for quantifying regional brain morphometry allow for automated quantification of tissue volumes in numerous distinct brain structures. We hypothesized that such quantitative structural information could help identify individuals more or less likely to benefit from memory rehabilitation. Fifty individuals with TBI of all severities who reported having memory difficulties first underwent structural MRI scanning. They then participated in a 12 session memory rehabilitation program emphasizing internal memory strategies (I-MEMS. Primary outcome measures (HVLT, RBMT were collected at the time of the MRI scan, immediately following therapy, and again at one month post-therapy. Regional brain volumes were used to predict outcome, adjusting for standard predictors (e.g., injury severity, age, education, pretest scores. We identified several brain regions that provided significant predictions of rehabilitation outcome, including the volume of the hippocampus, the lateral prefrontal cortex, the thalamus, and several subregions of the cingulate cortex. The prediction range of regional brain volumes were in some cases nearly equal in magnitude to prediction ranges provided by pretest scores on the outcome variable. We conclude that specific cerebral networks including these regions may contribute to learning during I-MEMS rehabilitation, and suggest that morphometric measures may provide substantial predictive value for rehabilitation outcome in other cognitive interventions as well.

  11. Age-and Brain Region-Specific Differences in Mitochondrial ...

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    Mitochondria are central regulators of energy homeostasis and play a pivotal role in mechanisms of cellular senescence. The objective of the present study was to evaluate mitochondrial bio­-energetic parameters in five brain regions [brainstem (BS), frontal cortex (FC), cerebellum (CER), striatum (STR), hippocampus (HIP)] of four diverse age groups [1 Month (young), 4 Month (adult), 12 Month (middle-aged), 24 Month (old age)] to understand age-related differences in selected brain regions and their contribution to age-related chemical sensitivity. Mitochondrial bioenergetics parameters and enzyme activity were measured under identical conditions across multiple age groups and brain regions in Brown Norway rats (n = 5). The results indicate age- and brain region-specific patterns in mitochondrial functional endpoints. For example, an age-specific decline in ATP synthesis (State 111 respiration) was observed in BS and HIP. Similarly, the maximal respiratory capacities (State V1 and V2) showed age-specific declines in all brain regions examined (young > adult > middle-aged > old age). Amongst all regions, HIP had the greatest change in mitochondrial bioenergetics, showing declines in the 4, 12 and 24 Month age groups. Activities of mitochondrial pyruvate dehydrogenase complex (PDHC) and electron transport chain (ETC) complexes I, II, and IV enzymes were also age- and brain-region specific. In general changes associated with age were more pronounced, with

  12. Fused cerebral organoids model interactions between brain regions.

    Science.gov (United States)

    Bagley, Joshua A; Reumann, Daniel; Bian, Shan; Lévi-Strauss, Julie; Knoblich, Juergen A

    2017-07-01

    Human brain development involves complex interactions between different regions, including long-distance neuronal migration or formation of major axonal tracts. Different brain regions can be cultured in vitro within 3D cerebral organoids, but the random arrangement of regional identities limits the reliable analysis of complex phenotypes. Here, we describe a coculture method combining brain regions of choice within one organoid tissue. By fusing organoids of dorsal and ventral forebrain identities, we generate a dorsal-ventral axis. Using fluorescent reporters, we demonstrate CXCR4-dependent GABAergic interneuron migration from ventral to dorsal forebrain and describe methodology for time-lapse imaging of human interneuron migration. Our results demonstrate that cerebral organoid fusion cultures can model complex interactions between different brain regions. Combined with reprogramming technology, fusions should offer researchers the possibility to analyze complex neurodevelopmental defects using cells from neurological disease patients and to test potential therapeutic compounds.

  13. Comparing brain graphs in which nodes are regions of interest or independent components: A simulation study.

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    Yu, Qingbao; Du, Yuhui; Chen, Jiayu; He, Hao; Sui, Jing; Pearlson, Godfrey; Calhoun, Vince D

    2017-11-01

    A key challenge in building a brain graph using fMRI data is how to define the nodes. Spatial brain components estimated by independent components analysis (ICA) and regions of interest (ROIs) determined by brain atlas are two popular methods to define nodes in brain graphs. It is difficult to evaluate which method is better in real fMRI data. Here we perform a simulation study and evaluate the accuracies of a few graph metrics in graphs with nodes of ICA components, ROIs, or modified ROIs in four simulation scenarios. Graph measures with ICA nodes are more accurate than graphs with ROI nodes in all cases. Graph measures with modified ROI nodes are modulated by artifacts. The correlations of graph metrics across subjects between graphs with ICA nodes and ground truth are higher than the correlations between graphs with ROI nodes and ground truth in scenarios with large overlapped spatial sources. Moreover, moving the location of ROIs would largely decrease the correlations in all scenarios. Evaluating graphs with different nodes is promising in simulated data rather than real data because different scenarios can be simulated and measures of different graphs can be compared with a known ground truth. Since ROIs defined using brain atlas may not correspond well to real functional boundaries, overall findings of this work suggest that it is more appropriate to define nodes using data-driven ICA than ROI approaches in real fMRI data. Copyright © 2017 Elsevier B.V. All rights reserved.

  14. Delineation of separate brain regions used for scientific versus engineering modes of thinking

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    Patterson, Clair C.

    1994-08-01

    nonutilitarian modes of thought. It is postulated that neuronal circuits involved in nonutilitarian modes of thought are located in specific regions of the brain that are divergent features between populations that have been territorially separated for tens of thousands of years. Anatomical PET and NMRI studies of brains of modern descendants of these cultures are proposed that would seek to define these inferred differences through proper protocols of stimulation devised by those investigators.

  15. Whole brain and brain regional coexpression network interactions associated with predisposition to alcohol consumption.

    Directory of Open Access Journals (Sweden)

    Lauren A Vanderlinden

    Full Text Available To identify brain transcriptional networks that may predispose an animal to consume alcohol, we used weighted gene coexpression network analysis (WGCNA. Candidate coexpression modules are those with an eigengene expression level that correlates significantly with the level of alcohol consumption across a panel of BXD recombinant inbred mouse strains, and that share a genomic region that regulates the module transcript expression levels (mQTL with a genomic region that regulates alcohol consumption (bQTL. To address a controversy regarding utility of gene expression profiles from whole brain, vs specific brain regions, as indicators of the relationship of gene expression to phenotype, we compared candidate coexpression modules from whole brain gene expression data (gathered with Affymetrix 430 v2 arrays in the Colorado laboratories and from gene expression data from 6 brain regions (nucleus accumbens (NA; prefrontal cortex (PFC; ventral tegmental area (VTA; striatum (ST; hippocampus (HP; cerebellum (CB available from GeneNetwork. The candidate modules were used to construct candidate eigengene networks across brain regions, resulting in three "meta-modules", composed of candidate modules from two or more brain regions (NA, PFC, ST, VTA and whole brain. To mitigate the potential influence of chromosomal location of transcripts and cis-eQTLs in linkage disequilibrium, we calculated a semi-partial correlation of the transcripts in the meta-modules with alcohol consumption conditional on the transcripts' cis-eQTLs. The function of transcripts that retained the correlation with the phenotype after correction for the strong genetic influence, implicates processes of protein metabolism in the ER and Golgi as influencing susceptibility to variation in alcohol consumption. Integration of these data with human GWAS provides further information on the function of polymorphisms associated with alcohol-related traits.

  16. Defining Optimal Brain Health in Adults: A Presidential Advisory From the American Heart Association/American Stroke Association.

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    Gorelick, Philip B; Furie, Karen L; Iadecola, Costantino; Smith, Eric E; Waddy, Salina P; Lloyd-Jones, Donald M; Bae, Hee-Joon; Bauman, Mary Ann; Dichgans, Martin; Duncan, Pamela W; Girgus, Meighan; Howard, Virginia J; Lazar, Ronald M; Seshadri, Sudha; Testai, Fernando D; van Gaal, Stephen; Yaffe, Kristine; Wasiak, Hank; Zerna, Charlotte

    2017-10-01

    Cognitive function is an important component of aging and predicts quality of life, functional independence, and risk of institutionalization. Advances in our understanding of the role of cardiovascular risks have shown them to be closely associated with cognitive impairment and dementia. Because many cardiovascular risks are modifiable, it may be possible to maintain brain health and to prevent dementia in later life. The purpose of this American Heart Association (AHA)/American Stroke Association presidential advisory is to provide an initial definition of optimal brain health in adults and guidance on how to maintain brain health. We identify metrics to define optimal brain health in adults based on inclusion of factors that could be measured, monitored, and modified. From these practical considerations, we identified 7 metrics to define optimal brain health in adults that originated from AHA's Life's Simple 7: 4 ideal health behaviors (nonsmoking, physical activity at goal levels, healthy diet consistent with current guideline levels, and body mass index brain health but recognize that the truly ideal circumstance may be uncommon because there is a continuum of brain health as demonstrated by AHA's Life's Simple 7. Therefore, there is opportunity to improve brain health through primordial prevention and other interventions. Furthermore, although cardiovascular risks align well with brain health, we acknowledge that other factors differing from those related to cardiovascular health may drive cognitive health. Defining optimal brain health in adults and its maintenance is consistent with the AHA's Strategic Impact Goal to improve cardiovascular health of all Americans by 20% and to reduce deaths resulting from cardiovascular disease and stroke by 20% by the year 2020. This work in defining optimal brain health in adults serves to provide the AHA/American Stroke Association with a foundation for a new strategic direction going forward in cardiovascular health

  17. Human capital in European peripheral regions: brain - drain and brain - gain

    NARCIS (Netherlands)

    Coenen, Franciscus H.J.M.

    2004-01-01

    Project goal - The overall goal of the project is to build a legitimate transnational network to transfer ideas and experiences and implement measures to reduce brain drain and foster brain gain while reinforcing the economical and spatial development of peripheral regions in NWE. This means a

  18. Brain region-dependent differential expression of alpha-synuclein.

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    Taguchi, Katsutoshi; Watanabe, Yoshihisa; Tsujimura, Atsushi; Tanaka, Masaki

    2016-04-15

    α-Synuclein, the major constituent of Lewy bodies (LBs), is normally expressed in presynapses and is involved in synaptic function. Abnormal intracellular aggregation of α-synuclein is observed as LBs and Lewy neurites in neurodegenerative disorders, such as Parkinson's disease (PD) or dementia with Lewy bodies. Accumulated evidence suggests that abundant intracellular expression of α-synuclein is one of the risk factors for pathological aggregation. Recently, we reported differential expression patterns of α-synuclein between excitatory and inhibitory hippocampal neurons. Here we further investigated the precise expression profile in the adult mouse brain with special reference to vulnerable regions along the progression of idiopathic PD. The results show that α-synuclein was highly expressed in the neuronal cell bodies of some early PD-affected brain regions, such as the olfactory bulb, dorsal motor nucleus of the vagus, and substantia nigra pars compacta. Synaptic expression of α-synuclein was mostly accompanied by expression of vesicular glutamate transporter-1, an excitatory presynaptic marker. In contrast, expression of α-synuclein in the GABAergic inhibitory synapses was different among brain regions. α-Synuclein was clearly expressed in inhibitory synapses in the external plexiform layer of the olfactory bulb, globus pallidus, and substantia nigra pars reticulata, but not in the cerebral cortex, subthalamic nucleus, or thalamus. These results suggest that some neurons in early PD-affected human brain regions express high levels of perikaryal α-synuclein, as happens in the mouse brain. Additionally, synaptic profiles expressing α-synuclein are different in various brain regions. © 2015 Wiley Periodicals, Inc.

  19. Neurons derived from different brain regions are inherently different in vitro: a novel multiregional brain-on-a-chip.

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    Dauth, Stephanie; Maoz, Ben M; Sheehy, Sean P; Hemphill, Matthew A; Murty, Tara; Macedonia, Mary Kate; Greer, Angie M; Budnik, Bogdan; Parker, Kevin Kit

    2017-03-01

    Brain in vitro models are critically important to developing our understanding of basic nervous system cellular physiology, potential neurotoxic effects of chemicals, and specific cellular mechanisms of many disease states. In this study, we sought to address key shortcomings of current brain in vitro models: the scarcity of comparative data for cells originating from distinct brain regions and the lack of multiregional brain in vitro models. We demonstrated that rat neurons from different brain regions exhibit unique profiles regarding their cell composition, protein expression, metabolism, and electrical activity in vitro. In vivo, the brain is unique in its structural and functional organization, and the interactions and communication between different brain areas are essential components of proper brain function. This fact and the observation that neurons from different areas of the brain exhibit unique behaviors in vitro underline the importance of establishing multiregional brain in vitro models. Therefore, we here developed a multiregional brain-on-a-chip and observed a reduction of overall firing activity, as well as altered amounts of astrocytes and specific neuronal cell types compared with separately cultured neurons. Furthermore, this multiregional model was used to study the effects of phencyclidine, a drug known to induce schizophrenia-like symptoms in vivo, on individual brain areas separately while monitoring downstream effects on interconnected regions. Overall, this work provides a comparison of cells from different brain regions in vitro and introduces a multiregional brain-on-a-chip that enables the development of unique disease models incorporating essential in vivo features. NEW & NOTEWORTHY Due to the scarcity of comparative data for cells from different brain regions in vitro, we demonstrated that neurons isolated from distinct brain areas exhibit unique behaviors in vitro. Moreover, in vivo proper brain function is dependent on the

  20. A Means for the Scintigraphic Imaging of Regional Brain Dynamics. Regional Cerebral Blood Flow and Regional Cerebral Blood Volume

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    Potchen, E. J.; Bentley, R.; Gerth, W.; Hill, R. L.; Davis, D. O. [Washington University School Of Medicine, St. Louis, MO (United States)

    1969-05-15

    The use of freely diffusable inert radioactive gas as a washout indicator to measure regional cerebral blood flow has become a standardized kinetic procedure in many laboratories. Recent investigations with this technique have led us to conclude that we can reliably distinguish regional flow with perfusion against regional flow without perfusion from the early portion of the curve. Based on a detailed study of the early curve kinetics in patients with and without cerebral vascular disease we have defined the sampling duration necessary for application of the Anger gamma camera imaging process to regional changes in cerebral radioactivity. Using a standard camera and a small computer, a procedure has been developed and based upon entire field to determine the time of maximum height followed by analysis of the data in a matrix. This will permit a contour plot presentation of calculated regional cerebral blood flow in millilitres per 100 grams perfused brain per minute. In addition, we propose to augment this data by the display of regional non-perfusion blood flow versus regional cerebral flow with perfusion. Preliminary investigation on sampling duration, and Compton scattering were prerequisite to clinical scintigraphy of regional cerebral blood flow. In addition, the method of interface for the conventional Anger gamma camera to digital computers used in this procedure are discussed. Applications to further assess regional cerebral dynamics by scintigraphy are presented. (author)

  1. Automated recognition of brain region mentions in neuroscience literature

    Directory of Open Access Journals (Sweden)

    Leon French

    2009-09-01

    Full Text Available The ability to computationally extract mentions of neuroanatomical regions from the literature would assist linking to other entities within and outside of an article. Examples include extracting reports of connectivity or region-specific gene expression. To facilitate text mining of neuroscience literature we have created a corpus of manually annotated brain region mentions. The corpus contains 1,377 abstracts with 18,242 brain region annotations. Interannotator agreement was evaluated for a subset of the documents, and was 90.7% and 96.7% for strict and lenient matching respectively. We observed a large vocabulary of over 6,000 unique brain region terms and 17,000 words. For automatic extraction of brain region mentions we evaluated simple dictionary methods and complex natural language processing techniques. The dictionary methods based on neuroanatomical lexicons recalled 36% of the mentions with 57% precision. The best performance was achieved using a conditional random field (CRF with a rich feature set. Features were based on morphological, lexical, syntactic and contextual information. The CRF recalled 76% of mentions at 81% precision, by counting partial matches recall and precision increase to 86% and 92% respectively. We suspect a large amount of error is due to coordinating conjunctions, previously unseen words and brain regions of less commonly studied organisms. We found context windows, lemmatization and abbreviation expansion to be the most informative techniques. The corpus is freely available at http://www.chibi.ubc.ca/WhiteText/.

  2. Specific metabolomics adaptations define a differential regional vulnerability in the adult human cerebral cortex

    Directory of Open Access Journals (Sweden)

    Rosanna Cabré

    2016-12-01

    Full Text Available Brain neurons offer diverse responses to stresses and detrimental factors during development and aging, and as a result of both neurodegenerative and neuropsychiatric disorders. This multiplicity of responses can be ascribed to the great diversity among neuronal populations. Here we have determined the metabolomic profile of three healthy adult human brain regions—entorhinal cortex, hippocampus, and frontal cortex—using mass spectrometry-based technologies. Our results show the existence of a lessened energy demand, mitochondrial stress, and lower one-carbon metabolism (particularly restricted to the methionine cycle specifically in frontal cortex. These findings, along with the better antioxidant capacity and lower mTOR signaling also seen in frontal cortex, suggest that this brain region is especially resistant to stress compared to the entorhinal cortex and hippocampus, which are more vulnerable regions. Globally, our results show the presence of specific metabolomics adaptations in three mature, healthy human brain regions, confirming the existence of cross-regional differences in cell vulnerability in the human cerebral cortex.

  3. Regional Brain Shrinkage over Two Years: Individual Differences and Effects of Pro-Inflammatory Genetic Polymorphisms

    Science.gov (United States)

    Persson, N.; Ghisletta, P.; Dahle, C.L.; Bender, A.R.; Yang, Y.; Yuan, P.; Daugherty, A.M.; Raz, N.

    2014-01-01

    We examined regional changes in brain volume in healthy adults (N = 167, age 19-79 years at baseline; N = 90 at follow-up) over approximately two years. With latent change score models, we evaluated mean change and individual differences in rates of change in 10 anatomically-defined and manually-traced regions of interest (ROIs): lateral prefrontal cortex (LPFC), orbital frontal cortex (OF), prefrontal white matter (PFw), hippocampus (HC), parahippocampal gyrus (PhG), caudate nucleus (Cd), putamen (Pt), insula (In), cerebellar hemispheres (CbH), and primary visual cortex (VC). Significant mean shrinkage was observed in the HC, CbH, In, OF, and the PhG, and individual differences in change were noted in all regions, except the OF. Pro-inflammatory genetic variants mediated shrinkage in PhG and CbH. Carriers of two T alleles of interleukin-1β (IL-1βC-511T, rs16944) and a T allele of methylenetetrahydrofolate reductase (MTHFRC677T, rs1801133) polymorphisms showed increased PhG shrinkage. No effects of a pro-inflammatory polymorphism for C-reactive protein (CRP-286C>A>T, rs3091244) or apolipoprotein (APOE) ε4 allele were noted. These results replicate the pattern of brain shrinkage observed in previous studies, with a notable exception of the LPFC thus casting doubt on the unique importance of prefrontal cortex in aging. Larger baseline volumes of CbH and In were associated with increased shrinkage, in conflict with the brain reserve hypothesis. Contrary to previous reports, we observed no significant linear effects of age and hypertension on regional brain shrinkage. Our findings warrant further investigation of the effects of neuroinflammation on structural brain change throughout the lifespan. PMID:25264227

  4. Brain regions involved in observing and trying to interpret dog behaviour.

    Science.gov (United States)

    Desmet, Charlotte; van der Wiel, Alko; Brass, Marcel

    2017-01-01

    Humans and dogs have interacted for millennia. As a result, humans (and especially dog owners) sometimes try to interpret dog behaviour. While there is extensive research on the brain regions that are involved in mentalizing about other peoples' behaviour, surprisingly little is known of whether we use these same brain regions to mentalize about animal behaviour. In this fMRI study we investigate whether brain regions involved in mentalizing about human behaviour are also engaged when observing dog behaviour. Here we show that these brain regions are more engaged when observing dog behaviour that is difficult to interpret compared to dog behaviour that is easy to interpret. Interestingly, these results were not only obtained when participants were instructed to infer reasons for the behaviour but also when they passively viewed the behaviour, indicating that these brain regions are activated by spontaneous mentalizing processes.

  5. 36 CFR 261.73 - Regulations applicable to Region 3, Southwestern Region, as defined in § 200.2. [Reserved

    Science.gov (United States)

    2010-07-01

    ... 36 Parks, Forests, and Public Property 2 2010-07-01 2010-07-01 false Regulations applicable to Region 3, Southwestern Region, as defined in § 200.2. [Reserved] 261.73 Section 261.73 Parks, Forests... § 261.73 Regulations applicable to Region 3, Southwestern Region, as defined in § 200.2. [Reserved] ...

  6. Novel method to ascertain chromatin accessibility at specific genomic loci from frozen brain homogenates and laser capture microdissected defined cells.

    Science.gov (United States)

    Delvaux, Elaine; Mastroeni, Diego; Nolz, Jennifer; Coleman, Paul D

    2016-06-01

    We describe a novel method for assessing the "open" or "closed" state of chromatin at selected locations within the genome. This method combines the use of Benzonase, which can digest DNA in the presence of actin, with qPCR to define digested regions. We demonstrate the application of this method in brain homogenates and laser captured cells. We also demonstrate application to selected sites within more than one gene and multiple sites within one gene. We demonstrate the validity of the method by treating cells with valproate, known to render chromatin more permissive, and by comparison with classical digestion with DNase I in an in vitro preparation. Although we demonstrate the use of this method in brain tissue we also recognize its applicability to other tissue types.

  7. Quantitative expression profile of distinct functional regions in the adult mouse brain.

    Directory of Open Access Journals (Sweden)

    Takeya Kasukawa

    Full Text Available The adult mammalian brain is composed of distinct regions with specialized roles including regulation of circadian clocks, feeding, sleep/awake, and seasonal rhythms. To find quantitative differences of expression among such various brain regions, we conducted the BrainStars (B* project, in which we profiled the genome-wide expression of ∼50 small brain regions, including sensory centers, and centers for motion, time, memory, fear, and feeding. To avoid confounds from temporal differences in gene expression, we sampled each region every 4 hours for 24 hours, and pooled the samples for DNA-microarray assays. Therefore, we focused on spatial differences in gene expression. We used informatics to identify candidate genes with expression changes showing high or low expression in specific regions. We also identified candidate genes with stable expression across brain regions that can be used as new internal control genes, and ligand-receptor interactions of neurohormones and neurotransmitters. Through these analyses, we found 8,159 multi-state genes, 2,212 regional marker gene candidates for 44 small brain regions, 915 internal control gene candidates, and 23,864 inferred ligand-receptor interactions. We also found that these sets include well-known genes as well as novel candidate genes that might be related to specific functions in brain regions. We used our findings to develop an integrated database (http://brainstars.org/ for exploring genome-wide expression in the adult mouse brain, and have made this database openly accessible. These new resources will help accelerate the functional analysis of the mammalian brain and the elucidation of its regulatory network systems.

  8. Central region morphometry in a child brain; Age and gender ...

    African Journals Online (AJOL)

    Background: Data on central region morphometry of a child brain is important not only in terms of providing us with information about central region anatomy of the brain but also in terms of the help of this information for the plans to be applied in neurosurgery. Objective: In the present study, central region morphometry of a ...

  9. Differentiating functional brain regions using optical coherence tomography (Conference Presentation)

    Science.gov (United States)

    Gil, Daniel A.; Bow, Hansen C.; Shen, Jin-H.; Joos, Karen M.; Skala, Melissa C.

    2017-02-01

    The human brain is made up of functional regions governing movement, sensation, language, and cognition. Unintentional injury during neurosurgery can result in significant neurological deficits and morbidity. The current standard for localizing function to brain tissue during surgery, intraoperative electrical stimulation or recording, significantly increases the risk, time, and cost of the procedure. There is a need for a fast, cost-effective, and high-resolution intraoperative technique that can avoid damage to functional brain regions. We propose that optical coherence tomography (OCT) can fill this niche by imaging differences in the cellular composition and organization of functional brain areas. We hypothesized this would manifest as differences in the attenuation coefficient measured using OCT. Five functional regions (prefrontal, somatosensory, auditory, visual, and cerebellum) were imaged in ex vivo porcine brains (n=3), a model chosen due to a similar white/gray matter ratio as human brains. The attenuation coefficient was calculated using a depth-resolved model and quantitatively validated with Intralipid phantoms across a physiological range of attenuation coefficients (absolute difference Nissl-stained histology will be used to validate our results and correlate OCT-measured attenuation coefficients to neuronal density. Additional development and validation of OCT algorithms to discriminate brain regions are planned to improve the safety and efficacy of neurosurgical procedures such as biopsy, electrode placement, and tissue resection.

  10. Carnosine reverses the aging-induced down regulation of brain regional serotonergic system.

    Science.gov (United States)

    Banerjee, Soumyabrata; Ghosh, Tushar K; Poddar, Mrinal K

    2015-12-01

    The purpose of the present investigation was to study the role of carnosine, an endogenous dipeptide biomolecule, on brain regional (cerebral cortex, hippocampus, hypothalamus and pons-medulla) serotonergic system during aging. Results showed an aging-induced brain region specific significant (a) increase in Trp (except cerebral cortex) and their 5-HIAA steady state level with an increase in their 5-HIAA accumulation and declination, (b) decrease in their both 5-HT steady state level and 5-HT accumulation (except cerebral cortex). A significant decrease in brain regional 5-HT/Trp ratio (except cerebral cortex) and increase in 5-HIAA/5-HT ratio were also observed during aging. Carnosine at lower dosages (0.5-1.0μg/Kg/day, i.t. for 21 consecutive days) didn't produce any significant response in any of the brain regions, but higher dosages (2.0-2.5μg/Kg/day, i.t. for 21 consecutive days) showed a significant response on those aging-induced brain regional serotonergic parameters. The treatment with carnosine (2.0μg/Kg/day, i.t. for 21 consecutive days), attenuated these brain regional aging-induced serotonergic parameters and restored towards their basal levels that observed in 4 months young control rats. These results suggest that carnosine attenuates and restores the aging-induced brain regional down regulation of serotonergic system towards that observed in young rats' brain regions. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

  11. Novel method to ascertain chromatin accessibility at specific genomic loci from frozen brain homogenates and laser capture microdissected defined cells

    Directory of Open Access Journals (Sweden)

    Elaine Delvaux

    2016-06-01

    Full Text Available We describe a novel method for assessing the “open” or “closed” state of chromatin at selected locations within the genome. This method combines the use of Benzonase, which can digest DNA in the presence of actin, with quantitative polymerase chain reaction to define digested regions. We demonstrate the application of this method in brain homogenates and laser captured cells. We also demonstrate application to selected sites within more than 1 gene and multiple sites within 1 gene. We demonstrate the validity of the method by treating cells with valproate, known to render chromatin more permissive, and by comparison with classical digestion with DNase I in an in vitro preparation. Although we demonstrate the use of this method in brain tissue, we also recognize its applicability to other tissue types.

  12. Regional distribution of serotonin transporter protein in postmortem human brain

    International Nuclear Information System (INIS)

    Kish, Stephen J.; Furukawa, Yoshiaki; Chang Lijan; Tong Junchao; Ginovart, Nathalie; Wilson, Alan; Houle, Sylvain; Meyer, Jeffrey H.

    2005-01-01

    Introduction: The primary approach in assessing the status of brain serotonin neurons in human conditions such as major depression and exposure to the illicit drug ecstasy has been the use of neuroimaging procedures involving radiotracers that bind to the serotonin transporter (SERT). However, there has been no consistency in the selection of a 'SERT-free' reference region for the estimation of free and nonspecific binding, as occipital cortex, cerebellum and white matter have all been employed. Objective and Methods: To identify areas of human brain that might have very low SERT levels, we measured, by a semiquantitative Western blotting procedure, SERT protein immunoreactivity throughout the postmortem brain of seven normal adult subjects. Results: Serotonin transporter could be quantitated in all examined brain areas. However, the SERT concentration in cerebellar cortex and white matter were only at trace values, being approximately 20% of average cerebral cortex and 5% of average striatum values. Conclusion: Although none of the examined brain areas are completely free of SERT, human cerebellar cortex has low SERT binding as compared to other examined brain regions, with the exception of white matter. Since the cerebellar cortical SERT binding is not zero, this region will not be a suitable reference region for SERT radioligands with very low free and nonspecific binding. For SERT radioligands with reasonably high free and nonspecific binding, the cerebellar cortex should be a useful reference region, provided other necessary radioligand assumptions are met

  13. Regional distribution of serotonin transporter protein in postmortem human brain

    Energy Technology Data Exchange (ETDEWEB)

    Kish, Stephen J. [Human Neurochemical Pathology Laboratory, Centre for Addiction and Mental Health, Toronto, ON, M5T 1R8 (Canada)]. E-mail: Stephen_Kish@CAMH.net; Furukawa, Yoshiaki [Human Neurochemical Pathology Laboratory, Centre for Addiction and Mental Health, Toronto, ON, M5T 1R8 (Canada); Chang Lijan [Human Neurochemical Pathology Laboratory, Centre for Addiction and Mental Health, Toronto, ON, M5T 1R8 (Canada); Tong Junchao [Human Neurochemical Pathology Laboratory, Centre for Addiction and Mental Health, Toronto, ON, M5T 1R8 (Canada); Ginovart, Nathalie [PET Centre, Centre for Addiction and Mental Health, Toronto, ON, M5T 1R8 (Canada); Wilson, Alan [PET Centre, Centre for Addiction and Mental Health, Toronto, ON, M5T 1R8 (Canada); Houle, Sylvain [PET Centre, Centre for Addiction and Mental Health, Toronto, ON, M5T 1R8 (Canada); Meyer, Jeffrey H. [PET Centre, Centre for Addiction and Mental Health, Toronto, ON, M5T 1R8 (Canada)

    2005-02-01

    Introduction: The primary approach in assessing the status of brain serotonin neurons in human conditions such as major depression and exposure to the illicit drug ecstasy has been the use of neuroimaging procedures involving radiotracers that bind to the serotonin transporter (SERT). However, there has been no consistency in the selection of a 'SERT-free' reference region for the estimation of free and nonspecific binding, as occipital cortex, cerebellum and white matter have all been employed. Objective and Methods: To identify areas of human brain that might have very low SERT levels, we measured, by a semiquantitative Western blotting procedure, SERT protein immunoreactivity throughout the postmortem brain of seven normal adult subjects. Results: Serotonin transporter could be quantitated in all examined brain areas. However, the SERT concentration in cerebellar cortex and white matter were only at trace values, being approximately 20% of average cerebral cortex and 5% of average striatum values. Conclusion: Although none of the examined brain areas are completely free of SERT, human cerebellar cortex has low SERT binding as compared to other examined brain regions, with the exception of white matter. Since the cerebellar cortical SERT binding is not zero, this region will not be a suitable reference region for SERT radioligands with very low free and nonspecific binding. For SERT radioligands with reasonably high free and nonspecific binding, the cerebellar cortex should be a useful reference region, provided other necessary radioligand assumptions are met.

  14. Automated selection of brain regions for real-time fMRI brain-computer interfaces

    Science.gov (United States)

    Lührs, Michael; Sorger, Bettina; Goebel, Rainer; Esposito, Fabrizio

    2017-02-01

    Objective. Brain-computer interfaces (BCIs) implemented with real-time functional magnetic resonance imaging (rt-fMRI) use fMRI time-courses from predefined regions of interest (ROIs). To reach best performances, localizer experiments and on-site expert supervision are required for ROI definition. To automate this step, we developed two unsupervised computational techniques based on the general linear model (GLM) and independent component analysis (ICA) of rt-fMRI data, and compared their performances on a communication BCI. Approach. 3 T fMRI data of six volunteers were re-analyzed in simulated real-time. During a localizer run, participants performed three mental tasks following visual cues. During two communication runs, a letter-spelling display guided the subjects to freely encode letters by performing one of the mental tasks with a specific timing. GLM- and ICA-based procedures were used to decode each letter, respectively using compact ROIs and whole-brain distributed spatio-temporal patterns of fMRI activity, automatically defined from subject-specific or group-level maps. Main results. Letter-decoding performances were comparable to supervised methods. In combination with a similarity-based criterion, GLM- and ICA-based approaches successfully decoded more than 80% (average) of the letters. Subject-specific maps yielded optimal performances. Significance. Automated solutions for ROI selection may help accelerating the translation of rt-fMRI BCIs from research to clinical applications.

  15. Improving Brain Magnetic Resonance Image (MRI Segmentation via a Novel Algorithm based on Genetic and Regional Growth

    Directory of Open Access Journals (Sweden)

    Javadpour A.

    2016-06-01

    Full Text Available Background: Regarding the importance of right diagnosis in medical applications, various methods have been exploited for processing medical images solar. The method of segmentation is used to analyze anal to miscall structures in medical imaging. Objective: This study describes a new method for brain Magnetic Resonance Image (MRI segmentation via a novel algorithm based on genetic and regional growth. Methods: Among medical imaging methods, brains MRI segmentation is important due to high contrast of non-intrusive soft tissue and high spatial resolution. Size variations of brain tissues are often accompanied by various diseases such as Alzheimer’s disease. As our knowledge about the relation between various brain diseases and deviation of brain anatomy increases, MRI segmentation is exploited as the first step in early diagnosis. In this paper, regional growth method and auto-mate selection of initial points by genetic algorithm is used to introduce a new method for MRI segmentation. Primary pixels and similarity criterion are automatically by genetic algorithms to maximize the accuracy and validity in image segmentation. Results: By using genetic algorithms and defining the fixed function of image segmentation, the initial points for the algorithm were found. The proposed algorithms are applied to the images and results are manually selected by regional growth in which the initial points were compared. The results showed that the proposed algorithm could reduce segmentation error effectively. Conclusion: The study concluded that the proposed algorithm could reduce segmentation error effectively and help us to diagnose brain diseases.

  16. Background field removal using a region adaptive kernel for quantitative susceptibility mapping of human brain

    Science.gov (United States)

    Fang, Jinsheng; Bao, Lijun; Li, Xu; van Zijl, Peter C. M.; Chen, Zhong

    2017-08-01

    Background field removal is an important MR phase preprocessing step for quantitative susceptibility mapping (QSM). It separates the local field induced by tissue magnetic susceptibility sources from the background field generated by sources outside a region of interest, e.g. brain, such as air-tissue interface. In the vicinity of air-tissue boundary, e.g. skull and paranasal sinuses, where large susceptibility variations exist, present background field removal methods are usually insufficient and these regions often need to be excluded by brain mask erosion at the expense of losing information of local field and thus susceptibility measures in these regions. In this paper, we propose an extension to the variable-kernel sophisticated harmonic artifact reduction for phase data (V-SHARP) background field removal method using a region adaptive kernel (R-SHARP), in which a scalable spherical Gaussian kernel (SGK) is employed with its kernel radius and weights adjustable according to an energy "functional" reflecting the magnitude of field variation. Such an energy functional is defined in terms of a contour and two fitting functions incorporating regularization terms, from which a curve evolution model in level set formation is derived for energy minimization. We utilize it to detect regions of with a large field gradient caused by strong susceptibility variation. In such regions, the SGK will have a small radius and high weight at the sphere center in a manner adaptive to the voxel energy of the field perturbation. Using the proposed method, the background field generated from external sources can be effectively removed to get a more accurate estimation of the local field and thus of the QSM dipole inversion to map local tissue susceptibility sources. Numerical simulation, phantom and in vivo human brain data demonstrate improved performance of R-SHARP compared to V-SHARP and RESHARP (regularization enabled SHARP) methods, even when the whole paranasal sinus regions

  17. Auditory motion in the sighted and blind: Early visual deprivation triggers a large-scale imbalance between auditory and "visual" brain regions.

    Science.gov (United States)

    Dormal, Giulia; Rezk, Mohamed; Yakobov, Esther; Lepore, Franco; Collignon, Olivier

    2016-07-01

    How early blindness reorganizes the brain circuitry that supports auditory motion processing remains controversial. We used fMRI to characterize brain responses to in-depth, laterally moving, and static sounds in early blind and sighted individuals. Whole-brain univariate analyses revealed that the right posterior middle temporal gyrus and superior occipital gyrus selectively responded to both in-depth and laterally moving sounds only in the blind. These regions overlapped with regions selective for visual motion (hMT+/V5 and V3A) that were independently localized in the sighted. In the early blind, the right planum temporale showed enhanced functional connectivity with right occipito-temporal regions during auditory motion processing and a concomitant reduced functional connectivity with parietal and frontal regions. Whole-brain searchlight multivariate analyses demonstrated higher auditory motion decoding in the right posterior middle temporal gyrus in the blind compared to the sighted, while decoding accuracy was enhanced in the auditory cortex bilaterally in the sighted compared to the blind. Analyses targeting individually defined visual area hMT+/V5 however indicated that auditory motion information could be reliably decoded within this area even in the sighted group. Taken together, the present findings demonstrate that early visual deprivation triggers a large-scale imbalance between auditory and "visual" brain regions that typically support the processing of motion information. Copyright © 2016 Elsevier Inc. All rights reserved.

  18. Multiple determinants of whole and regional brain volume among terrestrial carnivorans.

    Directory of Open Access Journals (Sweden)

    Eli M Swanson

    Full Text Available Mammalian brain volumes vary considerably, even after controlling for body size. Although several hypotheses have been proposed to explain this variation, most research in mammals on the evolution of encephalization has focused on primates, leaving the generality of these explanations uncertain. Furthermore, much research still addresses only one hypothesis at a time, despite the demonstrated importance of considering multiple factors simultaneously. We used phylogenetic comparative methods to investigate simultaneously the importance of several factors previously hypothesized to be important in neural evolution among mammalian carnivores, including social complexity, forelimb use, home range size, diet, life history, phylogeny, and recent evolutionary changes in body size. We also tested hypotheses suggesting roles for these variables in determining the relative volume of four brain regions measured using computed tomography. Our data suggest that, in contrast to brain size in primates, carnivoran brain size may lag behind body size over evolutionary time. Moreover, carnivore species that primarily consume vertebrates have the largest brains. Although we found no support for a role of social complexity in overall encephalization, relative cerebrum volume correlated positively with sociality. Finally, our results support negative relationships among different brain regions after accounting for overall endocranial volume, suggesting that increased size of one brain regions is often accompanied by reduced size in other regions rather than overall brain expansion.

  19. Predicting Alzheimer's disease by classifying 3D-Brain MRI images using SVM and other well-defined classifiers

    International Nuclear Information System (INIS)

    Matoug, S; Abdel-Dayem, A; Passi, K; Gross, W; Alqarni, M

    2012-01-01

    Alzheimer's disease (AD) is the most common form of dementia affecting seniors age 65 and over. When AD is suspected, the diagnosis is usually confirmed with behavioural assessments and cognitive tests, often followed by a brain scan. Advanced medical imaging and pattern recognition techniques are good tools to create a learning database in the first step and to predict the class label of incoming data in order to assess the development of the disease, i.e., the conversion from prodromal stages (mild cognitive impairment) to Alzheimer's disease, which is the most critical brain disease for the senior population. Advanced medical imaging such as the volumetric MRI can detect changes in the size of brain regions due to the loss of the brain tissues. Measuring regions that atrophy during the progress of Alzheimer's disease can help neurologists in detecting and staging the disease. In the present investigation, we present a pseudo-automatic scheme that reads volumetric MRI, extracts the middle slices of the brain region, performs segmentation in order to detect the region of brain's ventricle, generates a feature vector that characterizes this region, creates an SQL database that contains the generated data, and finally classifies the images based on the extracted features. For our results, we have used the MRI data sets from the Alzheimer's Disease Neuroimaging Initiative (ADNI) database.

  20. Regional brain distribution of toluene in rats and in a human autopsy

    Energy Technology Data Exchange (ETDEWEB)

    Ameno, Kiyoshi; Kiriu, Takahiro; Fuke, Chiaki; Ameno, Setsuko; Shinohara, Toyohiko; Ijiri, Iwao (Kagawa Medical School (Japan). Dept. of Forensic Medicine)

    1992-02-01

    Toluene concentrations in 9 brain regions of acutely exposed rats and that in 11 brain regions of a human case who inhaled toluene prior to death are described. After exposure to toluene by inhalation (2000 or 10 000 ppm) for 0.5 h or by oral dosing (400 mg/kg.), rats were killed by decapitation 0.5 and 4 h after onset of inhalation and 2 and 10 h after oral ingestion. After each experimental condition the highest range of brain region/blood toluene concentration ratio (BBCR) was in the brain stem regions (2.85-3.22) such as the pons and medulla oblongata, the middle range (1.77-2.12) in the midbrain, thalamus, caudate-putamen, hypothalamus and cerebellum, and the lowest range (1.22-1.64) in the hippocampus and cerebral cortex. These distribution patterns were quite constant. Toluene concentration in various brain regions were unevenly distributed and directly related blood levels. In a human case who had inhaled toluene vapor, the distribution among brain regions was relatively similar to that in rats, the highest concentration ratios being in the corpus callosum (BBCR:2.66) and the lowest in the hippocampus (BBCR:1.47). (orig.).

  1. AUTOMATED CLASSIFICATION AND SEGREGATION OF BRAIN MRI IMAGES INTO IMAGES CAPTURED WITH RESPECT TO VENTRICULAR REGION AND EYE-BALL REGION

    Directory of Open Access Journals (Sweden)

    C. Arunkumar

    2014-05-01

    Full Text Available Magnetic Resonance Imaging (MRI images of the brain are used for detection of various brain diseases including tumor. In such cases, classification of MRI images captured with respect to ventricular and eye ball regions helps in automated location and classification of such diseases. The methods employed in the paper can segregate the given MRI images of brain into images of brain captured with respect to ventricular region and images of brain captured with respect to eye ball region. First, the given MRI image of brain is segmented using Particle Swarm Optimization (PSO algorithm, which is an optimized algorithm for MRI image segmentation. The algorithm proposed in the paper is then applied on the segmented image. The algorithm detects whether the image consist of a ventricular region or an eye ball region and classifies it accordingly.

  2. A voxelwise approach to determine consensus regions-of-interest for the study of brain network plasticity

    Directory of Open Access Journals (Sweden)

    Sarah M. Rajtmajer

    2015-07-01

    Full Text Available Despite exciting advances in the functional imaging of the brain, it remains a challenge to define regions of interest (ROIs that do not require investigator supervision and permit examination of change in networks over time (or plasticity. Plasticity is most readily examined by maintaining ROIs constant via seed-based and anatomical-atlas based techniques, but these approaches are not data-driven, requiring definition based on prior experience (e.g. choice of seed-region, anatomical landmarks. These approaches are limiting especially when functional connectivity may evolve over time in areas that are finer than known anatomical landmarks or in areas outside predetermined seeded regions. An ideal method would permit investigators to study network plasticity due to learning, maturation effects, or clinical recovery via multiple time point data that can be compared to one another in the same ROI while also preserving the voxel-level data in those ROIs at each time point. Data-driven approaches (e.g., whole-brain voxelwise approaches ameliorate concerns regarding investigator bias, but the fundamental problem of comparing the results between distinct data sets remains. In this paper we propose an approach, aggregate-initialized label propagation (AILP, which allows for data at separate time points to be compared for examining developmental processes resulting in network change (plasticity. To do so, we use a whole-brain modularity approach to parcellate the brain into anatomically constrained functional modules at separate time points and then apply the AILP algorithm to form a consensus set of ROIs for examining change over time. To demonstrate its utility, we make use of a known dataset of individuals with traumatic brain injury sampled at two time points during the first year of recovery and show how the AILP procedure can be applied to select regions of interest to be used in a graph theoretical analysis of plasticity.

  3. Central region morphometry in a child brain; Age and gender ...

    African Journals Online (AJOL)

    2013-10-10

    Oct 10, 2013 ... Background: Data on central region morphometry of a child brain is important not only in terms of ... brain volume reaches the peak at the age of 14.5 in men ..... child and adolescent brain and effects of genetic variation.

  4. Defining treatment for brain metastases patients: nihilism versus optimism.

    Science.gov (United States)

    Craighead, Peter S; Chan, Alexander

    2012-02-01

    Treatment of brain metastases patients has included whole brain radiotherapy (WBRT) for over 50 years, and there is much data showing this to be associated with short-term gains. The integration of resection and radiosurgery to these patients allows some better prognostic groups to experience long-term local control and improvement in quality of life. The recursive partitioning analysis of the Radiation Therapy Oncology Group (RTOG) has been used as a predictive model for over a decade to identify three classes of patients. Number of lesions has been used to define treatment for a good prognostic subgroup that is eligible for surgery or radiosurgery, but there are few prospective studies of poorer prognosis brain metastases patients to evaluate the influence of number of lesions on the prediction of outcome. We examined patient, treatment and outcome parameters of all brain metastases patients in a 5-year period so that we could measure outcome and evaluate various factors on survival. This was a population-based study of all brain metastases patients in Southern Alberta between 2000 and 2005. It used an Excel spreadsheet database and STATA 8 software to analyze outcomes. The study included 568 patients representing 4.4% of our radiotherapy population. Median age, performance status and distribution of primary disease sites were comparable with other large series. Overall survival for the whole group was 3.05 months. Independent factors predicting for improved overall survival included younger age, KPS <70, less than four lesions and the use of stereotactic radiosurgery. Presence of extracranial disease or persistence of primary disease did not adversely impact survival outcome. This series shows that the number of lesions is a strong predictor of outcome. Integration of this factor into a decision-making model allows for identification of not only good prognosis patients who will benefit from aggressive treatment but it also facilitates decision making for poorer

  5. Functional Connectivity of Multiple Brain Regions Required for the Consolidation of Social Recognition Memory.

    Science.gov (United States)

    Tanimizu, Toshiyuki; Kenney, Justin W; Okano, Emiko; Kadoma, Kazune; Frankland, Paul W; Kida, Satoshi

    2017-04-12

    Social recognition memory is an essential and basic component of social behavior that is used to discriminate familiar and novel animals/humans. Previous studies have shown the importance of several brain regions for social recognition memories; however, the mechanisms underlying the consolidation of social recognition memory at the molecular and anatomic levels remain unknown. Here, we show a brain network necessary for the generation of social recognition memory in mice. A mouse genetic study showed that cAMP-responsive element-binding protein (CREB)-mediated transcription is required for the formation of social recognition memory. Importantly, significant inductions of the CREB target immediate-early genes c-fos and Arc were observed in the hippocampus (CA1 and CA3 regions), medial prefrontal cortex (mPFC), anterior cingulate cortex (ACC), and amygdala (basolateral region) when social recognition memory was generated. Pharmacological experiments using a microinfusion of the protein synthesis inhibitor anisomycin showed that protein synthesis in these brain regions is required for the consolidation of social recognition memory. These findings suggested that social recognition memory is consolidated through the activation of CREB-mediated gene expression in the hippocampus/mPFC/ACC/amygdala. Network analyses suggested that these four brain regions show functional connectivity with other brain regions and, more importantly, that the hippocampus functions as a hub to integrate brain networks and generate social recognition memory, whereas the ACC and amygdala are important for coordinating brain activity when social interaction is initiated by connecting with other brain regions. We have found that a brain network composed of the hippocampus/mPFC/ACC/amygdala is required for the consolidation of social recognition memory. SIGNIFICANCE STATEMENT Here, we identify brain networks composed of multiple brain regions for the consolidation of social recognition memory. We

  6. The polygenic risk for bipolar disorder influences brain regional function relating to visual and default state processing of emotional information.

    Science.gov (United States)

    Dima, Danai; de Jong, Simone; Breen, Gerome; Frangou, Sophia

    2016-01-01

    Genome-wise association studies have identified a number of common single-nucleotide polymorphisms (SNPs), each of small effect, associated with risk to bipolar disorder (BD). Several risk-conferring SNPs have been individually shown to influence regional brain activation thus linking genetic risk for BD to altered brain function. The current study examined whether the polygenic risk score method, which models the cumulative load of all known risk-conferring SNPs, may be useful in the identification of brain regions whose function may be related to the polygenic architecture of BD. We calculated the individual polygenic risk score for BD (PGR-BD) in forty-one patients with the disorder, twenty-five unaffected first-degree relatives and forty-six unrelated healthy controls using the most recent Psychiatric Genomics Consortium data. Functional magnetic resonance imaging was used to define task-related brain activation patterns in response to facial affect and working memory processing. We found significant effects of the PGR-BD score on task-related activation irrespective of diagnostic group. There was a negative association between the PGR-BD score and activation in the visual association cortex during facial affect processing. In contrast, the PGR-BD score was associated with failure to deactivate the ventromedial prefrontal region of the default mode network during working memory processing. These results are consistent with the threshold-liability model of BD, and demonstrate the usefulness of the PGR-BD score in identifying brain functional alternations associated with vulnerability to BD. Additionally, our findings suggest that the polygenic architecture of BD is not regionally confined but impacts on the task-dependent recruitment of multiple brain regions.

  7. Defining a region of optimization based on engine usage data

    Science.gov (United States)

    Jiang, Li; Lee, Donghoon; Yilmaz, Hakan; Stefanopoulou, Anna

    2015-08-04

    Methods and systems for engine control optimization are provided. One or more operating conditions of a vehicle engine are detected. A value for each of a plurality of engine control parameters is determined based on the detected one or more operating conditions of the vehicle engine. A range of the most commonly detected operating conditions of the vehicle engine is identified and a region of optimization is defined based on the range of the most commonly detected operating conditions of the vehicle engine. The engine control optimization routine is initiated when the one or more operating conditions of the vehicle engine are within the defined region of optimization.

  8. Background field removal using a region adaptive kernel for quantitative susceptibility mapping of human brain.

    Science.gov (United States)

    Fang, Jinsheng; Bao, Lijun; Li, Xu; van Zijl, Peter C M; Chen, Zhong

    2017-08-01

    Background field removal is an important MR phase preprocessing step for quantitative susceptibility mapping (QSM). It separates the local field induced by tissue magnetic susceptibility sources from the background field generated by sources outside a region of interest, e.g. brain, such as air-tissue interface. In the vicinity of air-tissue boundary, e.g. skull and paranasal sinuses, where large susceptibility variations exist, present background field removal methods are usually insufficient and these regions often need to be excluded by brain mask erosion at the expense of losing information of local field and thus susceptibility measures in these regions. In this paper, we propose an extension to the variable-kernel sophisticated harmonic artifact reduction for phase data (V-SHARP) background field removal method using a region adaptive kernel (R-SHARP), in which a scalable spherical Gaussian kernel (SGK) is employed with its kernel radius and weights adjustable according to an energy "functional" reflecting the magnitude of field variation. Such an energy functional is defined in terms of a contour and two fitting functions incorporating regularization terms, from which a curve evolution model in level set formation is derived for energy minimization. We utilize it to detect regions of with a large field gradient caused by strong susceptibility variation. In such regions, the SGK will have a small radius and high weight at the sphere center in a manner adaptive to the voxel energy of the field perturbation. Using the proposed method, the background field generated from external sources can be effectively removed to get a more accurate estimation of the local field and thus of the QSM dipole inversion to map local tissue susceptibility sources. Numerical simulation, phantom and in vivo human brain data demonstrate improved performance of R-SHARP compared to V-SHARP and RESHARP (regularization enabled SHARP) methods, even when the whole paranasal sinus regions

  9. Region of interest evaluation of SPECT image reconstruction methods using a realistic brain phantom

    International Nuclear Information System (INIS)

    Xia, Weishi; Glick, S.J.; Soares, E.J.

    1996-01-01

    A realistic numerical brain phantom, developed by Zubal et al, was used for a region-of-interest evaluation of the accuracy and noise variance of the following SPECT reconstruction methods: (1) Maximum-Likelihood reconstruction using the Expectation-Maximization (ML-EM) algorithm; (2) an EM algorithm using ordered-subsets (OS-EM); (3) a re-scaled block iterative EM algorithm (RBI-EM); and (4) a filtered backprojection algorithm that uses a combination of the Bellini method for attenuation compensation and an iterative spatial blurring correction method using the frequency-distance principle (FDP). The Zubal phantom was made from segmented MRI slices of the brain, so that neuro-anatomical structures are well defined and indexed. Small regions-of-interest (ROIs) from the white matter, grey matter in the center of the brain and grey matter from the peripheral area of the brain were selected for the evaluation. Photon attenuation and distance-dependent collimator blurring were modeled. Multiple independent noise realizations were generated for two different count levels. The simulation study showed that the ROI bias measured for the EM-based algorithms decreased as the iteration number increased, and that the OS-EM and RBI-EM algorithms (16 and 64 subsets were used) achieved the equivalent accuracy of the ML-EM algorithm at about the same noise variance, with much fewer number of iterations. The Bellini-FDP restoration algorithm converged fast and required less computation per iteration. The ML-EM algorithm had a slightly better ROI bias vs. variance trade-off than the other algorithms

  10. Carnosine: effect on aging-induced increase in brain regional monoamine oxidase-A activity.

    Science.gov (United States)

    Banerjee, Soumyabrata; Poddar, Mrinal K

    2015-03-01

    Aging is a natural biological process associated with several neurological disorders along with the biochemical changes in brain. Aim of the present investigation is to study the effect of carnosine (0.5-2.5μg/kg/day, i.t. for 21 consecutive days) on aging-induced changes in brain regional (cerebral cortex, hippocampus, hypothalamus and pons-medulla) mitochondrial monoamine oxidase-A (MAO-A) activity with its kinetic parameters. The results of the present study are: (1) The brain regional mitochondrial MAO-A activity and their kinetic parameters (except in Km of pons-medulla) were significantly increased with the increase of age (4-24 months), (2) Aging-induced increase of brain regional MAO-A activity including its Vmax were attenuated with higher dosages of carnosine (1.0-2.5μg/kg/day) and restored toward the activity that observed in young, though its lower dosage (0.5μg/kg/day) were ineffective in these brain regional MAO-A activity, (3) Carnosine at higher dosage in young rats, unlike aged rats significantly inhibited all the brain regional MAO-A activity by reducing their only Vmax excepting cerebral cortex, where Km was also significantly enhanced. These results suggest that carnosine attenuated the aging-induced increase of brain regional MAO-A activity by attenuating its kinetic parameters and restored toward the results of MAO-A activity that observed in corresponding brain regions of young rats. Copyright © 2014 Elsevier Ireland Ltd and the Japan Neuroscience Society. All rights reserved.

  11. Segmentation of brain parenchymal regions into gray matter and white matter with Alzheimer's disease

    International Nuclear Information System (INIS)

    Tokunaga, Chiaki; Yoshiura, Takashi; Yamashita, Yasuo; Magome, Taiki; Honda, Hiroshi; Arimura, Hidetaka; Toyofuku, Fukai; Ohki, Masafumi

    2010-01-01

    It is very difficult and time consuming for neuroradiologists to estimate the degree of cerebral atrophy based on the volume of cortical regions etc. Our purpose of this study was to develop an automated segmentation of the brain parenchyma into gray and white matter regions with Alzheimer's disease (AD) in three-dimensional (3D) T1-weighted MR images. Our proposed method consisted of extraction of a brain parenchymal region based on a brain model matching and segmentation of the brain parenchyma into gray and white matter regions based on a fuzzy c-means (FCM) algorithm. We applied our proposed method to MR images of the whole brains obtained from 9 cases, including 4 clinically AD cases and 5 control cases. The mean volume percentage of a cortical region (41.7%) to a brain parenchymal region in AD patients was smaller than that (45.2%) in the control subjects (p=0.000462). (author)

  12. Genome-wide association studies of mri-defined brain infarcts: Meta-analysis from the charge consortium

    NARCIS (Netherlands)

    S. Debette (Stéphanie); J.C. Bis (Joshua); M. Fornage (Myriam); H.A. Schmid (Herbert); M.A. Ikram (Arfan); S. Sigurdsson (Stefan); G. Heiss (Gerardo); M.V. Struchalin (Maksim); A.V. Smith (Albert Vernon); A. van der Lugt (Aad); C. DeCarli (Charles); T. Lumley (Thomas); D.S. Knopman (David); C. Enzinger (Christian); G. Eiriksdottir (Gudny); P.J. Koudstaal (Peter Jan); A.L. DeStefano (Anita); B.M. Psaty (Bruce); C. Dufouil (Carole); D.J. Catellier (Diane); F. Fazekas (Franz); T. Aspelund (Thor); Y.S. Aulchenko (Yurii); A. Beiser (Alexa); J.I. Rotter (Jerome); C. Tzourio (Christophe); D.K. Shibata (Dean); M. Tscherner (Maria); T.B. Harris (Tamara); F. Rivadeneira Ramirez (Fernando); L.D. Atwood (Larry); K. Rice (Kenneth); R.F. Gottesman (Rebecca); M.A. van Buchem (Mark); A.G. Uitterlinden (André); M. Kelly-Hayes (Margaret); M. Cushman (Mary Ann); Y. Zhu (Yicheng); E.A. Boerwinkle (Eric); V. Gudnason (Vilmundur); A. Hofman (Albert); J.R. Romero (Jose Rafael); M.M.B. Breteler (Monique); R. Schmidt (Reinhold); L.J. Launer (Lenore); W.T. Longstreth Jr

    2010-01-01

    textabstractBackground and Purpose-Previous studies examining genetic associations with MRI-defined brain infarct have yielded inconsistent findings. We investigated genetic variation underlying covert MRI infarct in persons without histories of transient ischemic attack or stroke. We performed

  13. Strong influence of variable treatment on the performance of numerically defined ecological regions.

    Science.gov (United States)

    Snelder, Ton; Lehmann, Anthony; Lamouroux, Nicolas; Leathwick, John; Allenbach, Karin

    2009-10-01

    Numerical clustering has frequently been used to define hierarchically organized ecological regionalizations, but there has been little robust evaluation of their performance (i.e., the degree to which regions discriminate areas with similar ecological character). In this study we investigated the effect of the weighting and treatment of input variables on the performance of regionalizations defined by agglomerative clustering across a range of hierarchical levels. For this purpose, we developed three ecological regionalizations of Switzerland of increasing complexity using agglomerative clustering. Environmental data for our analysis were drawn from a 400 m grid and consisted of estimates of 11 environmental variables for each grid cell describing climate, topography and lithology. Regionalization 1 was defined from the environmental variables which were given equal weights. We used the same variables in Regionalization 2 but weighted and transformed them on the basis of a dissimilarity model that was fitted to land cover composition data derived for a random sample of cells from interpretation of aerial photographs. Regionalization 3 was a further two-stage development of Regionalization 2 where specific classifications, also weighted and transformed using dissimilarity models, were applied to 25 small scale "sub-domains" defined by Regionalization 2. Performance was assessed in terms of the discrimination of land cover composition for an independent set of sites using classification strength (CS), which measured the similarity of land cover composition within classes and the dissimilarity between classes. Regionalization 2 performed significantly better than Regionalization 1, but the largest gains in performance, compared to Regionalization 1, occurred at coarse hierarchical levels (i.e., CS did not increase significantly beyond the 25-region level). Regionalization 3 performed better than Regionalization 2 beyond the 25-region level and CS values continued to

  14. A quantitative magnetic resonance histology atlas of postnatal rat brain development with regional estimates of growth and variability.

    Science.gov (United States)

    Calabrese, Evan; Badea, Alexandra; Watson, Charles; Johnson, G Allan

    2013-05-01

    There has been growing interest in the role of postnatal brain development in the etiology of several neurologic diseases. The rat has long been recognized as a powerful model system for studying neuropathology and the safety of pharmacologic treatments. However, the complex spatiotemporal changes that occur during rat neurodevelopment remain to be elucidated. This work establishes the first magnetic resonance histology (MRH) atlas of the developing rat brain, with an emphasis on quantitation. The atlas comprises five specimens at each of nine time points, imaged with eight distinct MR contrasts and segmented into 26 developmentally defined brain regions. The atlas was used to establish a timeline of morphometric changes and variability throughout neurodevelopment and represents a quantitative database of rat neurodevelopment for characterizing rat models of human neurologic disease. Published by Elsevier Inc.

  15. Alterations in regional homogeneity of resting-state brain activity in internet gaming addicts

    Directory of Open Access Journals (Sweden)

    Dong Guangheng

    2012-08-01

    Full Text Available Abstract Backgrounds Internet gaming addiction (IGA, as a subtype of internet addiction disorder, is rapidly becoming a prevalent mental health concern around the world. The neurobiological underpinnings of IGA should be studied to unravel the potential heterogeneity of IGA. This study investigated the brain functions in IGA patients with resting-state fMRI. Methods Fifteen IGA subjects and fourteen healthy controls participated in this study. Regional homogeneity (ReHo measures were used to detect the abnormal functional integrations. Results Comparing to the healthy controls, IGA subjects show enhanced ReHo in brainstem, inferior parietal lobule, left posterior cerebellum, and left middle frontal gyrus. All of these regions are thought related with sensory-motor coordination. In addition, IGA subjects show decreased ReHo in temporal, occipital and parietal brain regions. These regions are thought responsible for visual and auditory functions. Conclusions Our results suggest that long-time online game playing enhanced the brain synchronization in sensory-motor coordination related brain regions and decreased the excitability in visual and auditory related brain regions.

  16. Generation of Regionally Specified Neural Progenitors and Functional Neurons from Human Embryonic Stem Cells under Defined Conditions

    Directory of Open Access Journals (Sweden)

    Agnete Kirkeby

    2012-06-01

    Full Text Available To model human neural-cell-fate specification and to provide cells for regenerative therapies, we have developed a method to generate human neural progenitors and neurons from human embryonic stem cells, which recapitulates human fetal brain development. Through the addition of a small molecule that activates canonical WNT signaling, we induced rapid and efficient dose-dependent specification of regionally defined neural progenitors ranging from telencephalic forebrain to posterior hindbrain fates. Ten days after initiation of differentiation, the progenitors could be transplanted to the adult rat striatum, where they formed neuron-rich and tumor-free grafts with maintained regional specification. Cells patterned toward a ventral midbrain (VM identity generated a high proportion of authentic dopaminergic neurons after transplantation. The dopamine neurons showed morphology, projection pattern, and protein expression identical to that of human fetal VM cells grafted in parallel. VM-patterned but not forebrain-patterned neurons released dopamine and reversed motor deficits in an animal model of Parkinson's disease.

  17. Regional cerebral blood flow in psychiatry: The resting and activated brains of schizophrenic patients

    International Nuclear Information System (INIS)

    Gur, R.E.

    1984-01-01

    The investigation of regional brain functioning in schizophrenia has been based on behavioral techniques. Although results are sometimes inconsistent, the behavioral observations suggest left hemispheric dysfunction and left hemispheric overreaction. Recent developments in neuroimaging technology make possible major refinements in assessing regional brain function. Both anatomical and physiological information now be used to study regional brain development in psychiatric disorders. This chapter describes the application of one method - the xenon-133 technique for measuring regional cerebral blood flow (rCBF) - in studying the resting and activated brains of schizoprenic patients

  18. Data mining a functional neuroimaging database for functional segregation in brain regions

    DEFF Research Database (Denmark)

    Nielsen, Finn Årup; Balslev, Daniela; Hansen, Lars Kai

    2006-01-01

    We describe a specialized neuroinformatic data mining technique in connection with a meta-analytic functional neuroimaging database: We mine for functional segregation within brain regions by identifying journal articles that report brain activations within the regions and clustering the abstract...

  19. Data mining a functional neuroimaging database for functional|segregation in brain regions

    DEFF Research Database (Denmark)

    Nielsen, Finn Årup

    2006-01-01

    We describe a specialized neuroinformatic data mining technique in connection with a meta-analytic functional neuroimaging database: We mine for functional segregation within brain regions by identifying journal articles that report brain activations within the regions and clustering the abstract...

  20. Predictive modeling of neuroanatomic structures for brain atrophy detection

    Science.gov (United States)

    Hu, Xintao; Guo, Lei; Nie, Jingxin; Li, Kaiming; Liu, Tianming

    2010-03-01

    In this paper, we present an approach of predictive modeling of neuroanatomic structures for the detection of brain atrophy based on cross-sectional MRI image. The underlying premise of applying predictive modeling for atrophy detection is that brain atrophy is defined as significant deviation of part of the anatomy from what the remaining normal anatomy predicts for that part. The steps of predictive modeling are as follows. The central cortical surface under consideration is reconstructed from brain tissue map and Regions of Interests (ROI) on it are predicted from other reliable anatomies. The vertex pair-wise distance between the predicted vertex and the true one within the abnormal region is expected to be larger than that of the vertex in normal brain region. Change of white matter/gray matter ratio within a spherical region is used to identify the direction of vertex displacement. In this way, the severity of brain atrophy can be defined quantitatively by the displacements of those vertices. The proposed predictive modeling method has been evaluated by using both simulated atrophies and MRI images of Alzheimer's disease.

  1. Continuous High Frequency Activity: A peculiar SEEG pattern related to specific brain regions

    Science.gov (United States)

    Melani, Federico; Zelmann, Rina; Mari, Francesco; Gotman, Jean

    2015-01-01

    Objective While visually marking the high frequency oscillations in the stereo-EEG of epileptic patients, we observed a continuous/semicontinuous activity in the ripple band (80–250 Hz), which we defined continuous High Frequency Activity (HFA). We aim to analyze in all brain regions the occurrence and significance of this particular pattern. Methods Twenty patients implanted in mesial temporal and neocortical areas were studied. One minute of slow-wave sleep was reviewed. The background was classified as continuous/semicontinuous, irregular, or sporadic based on the duration of the fast oscillations. Each channel was classified as inside/outside the seizure onset zone (SOZ) or a lesion. Results The continuous/semicontinuous HFA occurred in 54 of the 790 channels analyzed, with a clearly higher prevalence in hippocampus and occipital lobe. No correlation was found with the SOZ or lesions. In the occipital lobe the continuous/semicontinuous HFA was present independently of whether eyes were open or closed. Conclusions We describe what appears to be a new physiological High Frequency Activity, independent of epileptogenicity, present almost exclusively in the hippocampus and occipital cortex but independent of the alpha rhythm. Significance The continuous HFA may be an intrinsic characteristic of specific brain regions, reflecting a particular type of physiological neuronal activity. PMID:23768436

  2. Influence of ketamine on regional brain glucose use

    International Nuclear Information System (INIS)

    Davis, D.W.; Mans, A.M.; Biebuyck, J.F.; Hawkins, R.A.

    1988-01-01

    The purpose of this study was to determine the effect of different doses of ketamine on cerebral function at the level of individual brain structures as reflected by glucose use. Rats received either 5 or 30 mg/kg ketamine intravenously as a loading dose, followed by an infusion to maintain a steady-state level of the drug. An additional group received 30 mg/kg as a single injection only, and was studied 20 min later, by which time they were recovering consciousness (withdrawal group). Regional brain energy metabolism was evaluated with [6- 14 C]glucose and quantitative autoradiography during a 5-min experimental period. A subhypnotic, steady-state dose (5 mg/kg) of ketamine caused a stimulation of glucose use in most brain areas, with an average increase of 20%. At the larger steady-state dose (30 mg/kg, which is sufficient to cause anesthesia), there was no significant effect on most brain regions; some sensory nuclei were depressed (inferior colliculus, -29%; cerebellar dentate nucleus, -18%; vestibular nucleus, -16%), but glucose use in the ventral posterior hippocampus was increased by 33%. In contrast, during withdrawal from a 30-mg/kg bolus, there was a stimulation of glucose use throughout the brain (21-78%), at a time when plasma ketamine levels were similar to the levels in the 5 mg/kg group. At each steady-state dose, as well as during withdrawal, ketamine caused a notable stimulation of glucose use by the hippocampus

  3. Regional apparent diffusion coefficient values in 3rd trimester fetal brain

    International Nuclear Information System (INIS)

    Hoffmann, Chen; Weisz, Boaz; Lipitz, Shlomo; Katorza, Eldad; Yaniv, Gal; Bergman, Dafi; Biegon, Anat

    2014-01-01

    Apparent diffusion coefficient (ADC) values in the developing fetus can be used in the diagnosis and prognosis of prenatal brain pathologies. To this end, we measured regional ADC in a relatively large cohort of normal fetal brains in utero. Diffusion-weighted imaging (DWI) was performed in 48 non-sedated 3rd trimester fetuses with normal structural MR imaging results. ADC was measured in white matter (frontal, parietal, temporal, and occipital lobes), basal ganglia, thalamus, pons, and cerebellum. Regional ADC values were compared by one-way ANOVA with gestational age as covariate. Regression analysis was used to examine gestational age-related changes in regional ADC. Four other cases of CMV infection were also examined. Median gestational age was 32 weeks (range, 26-33 weeks). There was a highly significant effect of region on ADC, whereby ADC values were highest in white matter, with significantly lower values in basal ganglia and cerebellum and the lowest values in thalamus and pons. ADC did not significantly change with gestational age in any of the regions tested. In the four cases with fetal CMV infection, ADC value was associated with a global decrease. ADC values in normal fetal brain are relatively stable during the third trimester, show consistent regional variation, and can make an important contribution to the early diagnosis and possibly prognosis of fetal brain pathologies. (orig.)

  4. Regional apparent diffusion coefficient values in 3rd trimester fetal brain

    Energy Technology Data Exchange (ETDEWEB)

    Hoffmann, Chen [Tel Aviv University, Department of Radiology, Sheba Medical Center, Tel Hashomer (affiliated to the Sackler School of Medicine), Tel Aviv (Israel); Sheba Medical Center, Diagnostic Imaging, 52621, Tel Hashomer (Israel); Weisz, Boaz; Lipitz, Shlomo; Katorza, Eldad [Tel Aviv University, Department of Obstetrics and Gynecology, Sheba Medical Center, Tel Hashomer (affiliated to the Sackler School of Medicine), Tel Aviv (Israel); Yaniv, Gal; Bergman, Dafi [Tel Aviv University, Department of Radiology, Sheba Medical Center, Tel Hashomer (affiliated to the Sackler School of Medicine), Tel Aviv (Israel); Biegon, Anat [Stony Brook University School of Medicine, Department of Neurology, Stony Brook, NY (United States)

    2014-07-15

    Apparent diffusion coefficient (ADC) values in the developing fetus can be used in the diagnosis and prognosis of prenatal brain pathologies. To this end, we measured regional ADC in a relatively large cohort of normal fetal brains in utero. Diffusion-weighted imaging (DWI) was performed in 48 non-sedated 3rd trimester fetuses with normal structural MR imaging results. ADC was measured in white matter (frontal, parietal, temporal, and occipital lobes), basal ganglia, thalamus, pons, and cerebellum. Regional ADC values were compared by one-way ANOVA with gestational age as covariate. Regression analysis was used to examine gestational age-related changes in regional ADC. Four other cases of CMV infection were also examined. Median gestational age was 32 weeks (range, 26-33 weeks). There was a highly significant effect of region on ADC, whereby ADC values were highest in white matter, with significantly lower values in basal ganglia and cerebellum and the lowest values in thalamus and pons. ADC did not significantly change with gestational age in any of the regions tested. In the four cases with fetal CMV infection, ADC value was associated with a global decrease. ADC values in normal fetal brain are relatively stable during the third trimester, show consistent regional variation, and can make an important contribution to the early diagnosis and possibly prognosis of fetal brain pathologies. (orig.)

  5. Age-related differences in regional brain volumes: A comparison of optimized voxel-based morphometry to manual volumetry

    Science.gov (United States)

    Kennedy, Kristen M.; Erickson, Kirk I.; Rodrigue, Karen M.; Voss, Michelle W.; Colcombe, Stan J.; Kramer, Arthur F.; Acker, James D.; Raz, Naftali

    2009-01-01

    Regional manual volumetry is the gold standard of in vivo neuroanatomy, but is labor-intensive, can be imperfectly reliable, and allows for measuring limited number of regions. Voxel-based morphometry (VBM) has perfect repeatability and assesses local structure across the whole brain. However, its anatomic validity is unclear, and with its increasing popularity, a systematic comparison of VBM to manual volumetry is necessary. The few existing comparison studies are limited by small samples, qualitative comparisons, and limited selection and modest reliability of manual measures. Our goal was to overcome those limitations by quantitatively comparing optimized VBM findings with highly reliable multiple regional measures in a large sample (N = 200) across a wide agespan (18–81). We report a complex pattern of similarities and differences. Peak values of VBM volume estimates (modulated density) produced stronger age differences and a different spatial distribution from manual measures. However, when we aggregated VBM-derived information across voxels contained in specific anatomically defined regions (masks), the patterns of age differences became more similar, although important discrepancies emerged. Notably, VBM revealed stronger age differences in the regions bordering CSF and white matter areas prone to leukoaraiosis, and VBM was more likely to report nonlinearities in age-volume relationships. In the white matter regions, manual measures showed stronger negative associations with age than the corresponding VBM-based masks. We conclude that VBM provides realistic estimates of age differences in the regional gray matter only when applied to anatomically defined regions, but overestimates effects when individual peaks are interpreted. It may be beneficial to use VBM as a first-pass strategy, followed by manual measurement of anatomically-defined regions. PMID:18276037

  6. Defining competitiveness through the theories of new economic geography and regional economy

    Directory of Open Access Journals (Sweden)

    Vuković Darko

    2012-01-01

    Full Text Available The subject of work is defining competitiveness through a multidisciplinary approach of the theories of new economic geography and regional economy. The paper describes in detail the theory of competitiveness, defined by numerous authors in this area, with special emphasis on the opposing views of Michael Porter and Paul Krugman. A regional competitiveness that is colsely related to economic geography and regional economy, the development of regional economy and typology of regions have been defined in the work. One of the first authors that stressed the importance of geographical location was Michael Porter. In his model called “diamond“, the author emphasizes that geographical concentration of a business enhances the productivity, innovativity and sector export. After this theory, many authors have foccussed on the location problem research, which resulted in better interconnection of economy and geography. As the result of such activities, new directions have been developed, such as the new theory of economic geography and regional economy. New economic geography has been mentioned mostly in connection with the Nobel Prize winner, Paul Krugman, whose theories are often opposed to Porter's ones. Krugman had the most credit for the development of New Economic Geography. At the end of the work, the differences between comparative and competitive adventages were explained. [Projekat Ministarstva nauke Republike Srbije, br. 47007, br. 47009 i br. 179015

  7. Age- and brain region-dependent α-synuclein oligomerization is attributed to alterations in intrinsic enzymes regulating α-synuclein phosphorylation in aging monkey brains.

    Science.gov (United States)

    Chen, Min; Yang, Weiwei; Li, Xin; Li, Xuran; Wang, Peng; Yue, Feng; Yang, Hui; Chan, Piu; Yu, Shun

    2016-02-23

    We previously reported that the levels of α-syn oligomers, which play pivotal pathogenic roles in age-related Parkinson's disease (PD) and dementia with Lewy bodies, increase heterogeneously in the aging brain. Here, we show that exogenous α-syn incubated with brain extracts from older cynomolgus monkeys and in Lewy body pathology (LBP)-susceptible brain regions (striatum and hippocampus) forms higher amounts of phosphorylated and oligomeric α-syn than that in extracts from younger monkeys and LBP-insusceptible brain regions (cerebellum and occipital cortex). The increased α-syn phosphorylation and oligomerization in the brain extracts from older monkeys and in LBP-susceptible brain regions were associated with higher levels of polo-like kinase 2 (PLK2), an enzyme promoting α-syn phosphorylation, and lower activity of protein phosphatase 2A (PP2A), an enzyme inhibiting α-syn phosphorylation, in these brain extracts. Further, the extent of the age- and brain-dependent increase in α-syn phosphorylation and oligomerization was reduced by inhibition of PLK2 and activation of PP2A. Inversely, phosphorylated α-syn oligomers reduced the activity of PP2A and showed potent cytotoxicity. In addition, the activity of GCase and the levels of ceramide, a product of GCase shown to activate PP2A, were lower in brain extracts from older monkeys and in LBP-susceptible brain regions. Our results suggest a role for altered intrinsic metabolic enzymes in age- and brain region-dependent α-syn oligomerization in aging brains.

  8. Neuropeptide processing in regional brain slices: Effect of conformation and sequence

    Energy Technology Data Exchange (ETDEWEB)

    Li, Z.W.; Bijl, W.A.; van Nispen, J.W.; Brendel, K.; Davis, T.P. (Univ. of Arizona, Tucson (USA))

    1990-05-01

    The central enzymatic stability of des-enkephalin-gamma-endorphin and its synthetic analogs (cycloN alpha 6, C delta 11)beta-endorphin-(6-17) and (Pro7, Lys(Ac)9)-beta-endorphin(6-17) was studied in vitro using a newly developed, regionally dissected rat brain slice, time course incubation procedure. Tissue slice viability was estimated as the ability of the brain slice to take up or release gamma-(3H)aminobutyric acid after high K+ stimulation. Results demonstrated stability of uptake/release up to 5 hr of incubation, suggesting tissue viability over this period. The estimated half-life of peptides based on the results obtained in our incubation protocol suggest that the peptides studied are metabolized at different rates in the individual brain regions tested. A good correlation exists between the high enzyme activity of neutral endopeptidase and the rapid degradation of des-enkephalin-gamma-endorphin and (cycloN alpha 6, C delata 11)beta-endorphin-(6-17) in caudate putamen. Proline substitution combined with lysine acetylation appears to improve resistance to enzymatic metabolism in caudate putamen and hypothalamus. However, cyclization of des-enkephalin-gamma-endorphin forming an amide bond between the alpha-NH2 of the N-terminal threonine and the gamma-COOH of glutamic acid did not improve peptide stability in any brain region tested. The present study has shown that the brain slice technique is a valid and unique approach to study neuropeptide metabolism in small, discrete regions of rat brain where peptides, peptidases and receptors are colocalized and that specific structural modifications can improve peptide stability.

  9. Big Cat Coalitions: A Comparative Analysis of Regional Brain Volumes in Felidae.

    Science.gov (United States)

    Sakai, Sharleen T; Arsznov, Bradley M; Hristova, Ani E; Yoon, Elise J; Lundrigan, Barbara L

    2016-01-01

    Broad-based species comparisons across mammalian orders suggest a number of factors that might influence the evolution of large brains. However, the relationship between these factors and total and regional brain size remains unclear. This study investigated the relationship between relative brain size and regional brain volumes and sociality in 13 felid species in hopes of revealing relationships that are not detected in more inclusive comparative studies. In addition, a more detailed analysis was conducted of four focal species: lions ( Panthera leo ), leopards ( Panthera pardus ), cougars ( Puma concolor ), and cheetahs ( Acinonyx jubatus ). These species differ markedly in sociality and behavioral flexibility, factors hypothesized to contribute to increased relative brain size and/or frontal cortex size. Lions are the only truly social species, living in prides. Although cheetahs are largely solitary, males often form small groups. Both leopards and cougars are solitary. Of the four species, leopards exhibit the most behavioral flexibility, readily adapting to changing circumstances. Regional brain volumes were analyzed using computed tomography. Skulls ( n = 75) were scanned to create three-dimensional virtual endocasts, and regional brain volumes were measured using either sulcal or bony landmarks obtained from the endocasts or skulls. Phylogenetic least squares regression analyses found that sociality does not correspond with larger relative brain size in these species. However, the sociality/solitary variable significantly predicted anterior cerebrum (AC) volume, a region that includes frontal cortex. This latter finding is despite the fact that the two social species in our sample, lions and cheetahs, possess the largest and smallest relative AC volumes, respectively. Additionally, an ANOVA comparing regional brain volumes in four focal species revealed that lions and leopards, while not significantly different from one another, have relatively larger AC

  10. Big Cat Coalitions: A comparative analysis of regional brain volumes in Felidae

    Directory of Open Access Journals (Sweden)

    Sharleen T Sakai

    2016-10-01

    Full Text Available Broad-based species comparisons across mammalian orders suggest a number of factors that might influence the evolution of large brains. However, the relationship between these factors and total and regional brain size remains unclear. This study investigated the relationship between relative brain size and regional brain volumes and sociality in 13 felid species in hopes of revealing relationships that are not detected in more inclusive comparative studies. In addition, a more detailed analysis was conducted of 4 focal species: lions (Panthera leo, leopards (Panthera pardus, cougars (Puma concolor, and cheetahs (Acinonyx jubatus. These species differ markedly in sociality and behavioral flexibility, factors hypothesized to contribute to increased relative brain size and/or frontal cortex size. Lions are the only truly social species, living in prides. Although cheetahs are largely solitary, males often form small groups. Both leopards and cougars are solitary. Of the four species, leopards exhibit the most behavioral flexibility, readily adapting to changing circumstances. Regional brain volumes were analyzed using computed tomography (CT. Skulls (n=75 were scanned to create three-dimensional virtual endocasts, and regional brain volumes were measured using either sulcal or bony landmarks obtained from the endocasts or skulls. Phylogenetic least squares (PGLS regression analyses found that sociality does not correspond with larger relative brain size in these species. However, the sociality/solitary variable significantly predicted anterior cerebrum (AC volume, a region that includes frontal cortex. This latter finding is despite the fact that the two social species in our sample, lions and cheetahs, possess the largest and smallest relative AC volumes, respectively. Additionally, an ANOVA comparing regional brain volumes in 4 focal species revealed that lions and leopards, while not significantly different from one another, have relatively

  11. Brain noise is task dependent and region specific.

    Science.gov (United States)

    Misić, Bratislav; Mills, Travis; Taylor, Margot J; McIntosh, Anthony R

    2010-11-01

    The emerging organization of anatomical and functional connections during human brain development is thought to facilitate global integration of information. Recent empirical and computational studies have shown that this enhanced capacity for information processing enables a diversified dynamic repertoire that manifests in neural activity as irregularity and noise. However, transient functional networks unfold over multiple time, scales and the embedding of a particular region depends not only on development, but also on the manner in which sensory and cognitive systems are engaged. Here we show that noise is a facet of neural activity that is also sensitive to the task context and is highly region specific. Children (6-16 yr) and adults (20-41 yr) performed a one-back face recognition task with inverted and upright faces. Neuromagnetic activity was estimated at several hundred sources in the brain by applying a beamforming technique to the magnetoencephalogram (MEG). During development, neural activity became more variable across the whole brain, with most robust increases in medial parietal regions, such as the precuneus and posterior cingulate cortex. For young children and adults, activity evoked by upright faces was more variable and noisy compared with inverted faces, and this effect was reliable only in the right fusiform gyrus. These results are consistent with the notion that upright faces engender a variety of integrative neural computations, such as the relations among facial features and their holistic constitution. This study shows that transient changes in functional integration modulated by task demand are evident in the variability of regional neural activity.

  12. Acute and chronic changes in brain activity with deep brain stimulation for refractory depression.

    Science.gov (United States)

    Conen, Silke; Matthews, Julian C; Patel, Nikunj K; Anton-Rodriguez, José; Talbot, Peter S

    2018-04-01

    Deep brain stimulation is a potential option for patients with treatment-refractory depression. Deep brain stimulation benefits have been reported when targeting either the subgenual cingulate or ventral anterior capsule/nucleus accumbens. However, not all patients respond and optimum stimulation-site is uncertain. We compared deep brain stimulation of the subgenual cingulate and ventral anterior capsule/nucleus accumbens separately and combined in the same seven treatment-refractory depression patients, and investigated regional cerebral blood flow changes associated with acute and chronic deep brain stimulation. Deep brain stimulation-response was defined as reduction in Montgomery-Asberg Depression Rating Scale score from baseline of ≥50%, and remission as a Montgomery-Asberg Depression Rating Scale score ≤8. Changes in regional cerebral blood flow were assessed using [ 15 O]water positron emission tomography. Remitters had higher relative regional cerebral blood flow in the prefrontal cortex at baseline and all subsequent time-points compared to non-remitters and non-responders, with prefrontal cortex regional cerebral blood flow generally increasing with chronic deep brain stimulation. These effects were consistent regardless of stimulation-site. Overall, no significant regional cerebral blood flow changes were apparent when deep brain stimulation was acutely interrupted. Deep brain stimulation improved treatment-refractory depression severity in the majority of patients, with consistent changes in local and distant brain regions regardless of target stimulation. Remission of depression was reached in patients with higher baseline prefrontal regional cerebral blood flow. Because of the small sample size these results are preliminary and further evaluation is necessary to determine whether prefrontal cortex regional cerebral blood flow could be a predictive biomarker of treatment response.

  13. Exosomal biomarkers of brain insulin resistance associated with regional atrophy in Alzheimer's disease.

    Science.gov (United States)

    Mullins, Roger J; Mustapic, Maja; Goetzl, Edward J; Kapogiannis, Dimitrios

    2017-04-01

    Brain insulin resistance (IR), which depends on insulin-receptor-substrate-1 (IRS-1) phosphorylation, is characteristic of Alzheimer's disease (AD). Previously, we demonstrated higher pSer312-IRS-1 (ineffective insulin signaling) and lower p-panTyr-IRS-1 (effective insulin signaling) in neural origin-enriched plasma exosomes of AD patients vs. Here, we hypothesized that these exosomal biomarkers associate with brain atrophy in AD. We studied 24 subjects with biomarker-supported probable AD (low CSF Aβ 42 ). Exosomes were isolated from plasma, enriched for neural origin using immunoprecipitation for L1CAM, and measured for pSer 312 - and p-panTyr-IRS-1 phosphotypes. MPRAGE images were segmented by brain tissue type and voxel-based morphometry (VBM) analysis for gray matter against pSer 312 - and p-panTyr-IRS-1 was conducted. Given the regionally variable brain expression of IRS-1, we used the Allen Brain Atlas to make spatial comparisons between VBM results and IRS-1 expression. Brain volume was positively associated with P-panTyr-IRS-1 and negatively associated with pSer 312 -IRS-1 in a strikingly similar regional pattern (bilateral parietal-occipital junction, R middle temporal gyrus). This volumetric association pattern was spatially correlated with Allen Human Brain atlas normal brain IRS-1 expression. Exosomal biomarkers of brain IR are thus associated with atrophy in AD as could be expected by their pathophysiological roles and do so in a pattern that reflects regional IRS-1 expression. Furthermore, neural-origin plasma exosomes may recover molecular signals from specific brain regions. Hum Brain Mapp 38:1933-1940, 2017. © 2017 Wiley Periodicals, Inc. © 2016 Wiley Periodicals, Inc.

  14. Transfection of brain capillary endothelial cells in primary culture with defined blood-brain barrier properties.

    Science.gov (United States)

    Burkhart, Annette; Thomsen, Louiza Bohn; Thomsen, Maj Schneider; Lichota, Jacek; Fazakas, Csilla; Krizbai, István; Moos, Torben

    2015-08-07

    Primary brain capillary endothelial cells (BCECs) are a promising tool to study the blood-brain barrier (BBB) in vitro, as they maintain many important characteristics of the BBB in vivo, especially when co-cultured with pericytes and/or astrocytes. A novel strategy for drug delivery to the brain is to transform BCECs into protein factories by genetic modifications leading to secretion of otherwise BBB impermeable proteins into the central nervous system. However, a huge challenge underlying this strategy is to enable transfection of non-mitotic BCECs, taking a non-viral approach. We therefore aimed to study transfection in primary, non-mitotic BCECs cultured with defined BBB properties without disrupting the cells' integrity. Primary cultures of BCECs, pericytes and astrocytes were generated from rat brains and used in three different in vitro BBB experimental arrangements, which were characterised based on a their expression of tight junction proteins and other BBB specific proteins, high trans-endothelial electrical resistance (TEER), and low passive permeability to radiolabeled mannitol. Recombinant gene expression and protein synthesis were examined in primary BCECs. The BCECs were transfected using a commercially available transfection agent Turbofect™ to express the red fluorescent protein HcRed1-C1. The BCECs were transfected at different time points to monitor transfection in relation to mitotic or non-mitotic cells, as indicated by fluorescence-activated cell sorting analysis after 5-and 6-carboxylfluorescein diacetate succinidyl ester incorporation. The cell cultures exhibited important BBB characteristics judged from their expression of BBB specific proteins, high TEER values, and low passive permeability. Among the three in vitro BBB models, co-culturing with BCECs and astrocytes was well suited for the transfection studies. Transfection was independent of cell division and with equal efficacy between the mitotic and non-mitotic BCECs. Importantly

  15. Regional infant brain development: an MRI-based morphometric analysis in 3 to 13 month olds.

    Science.gov (United States)

    Choe, Myong-Sun; Ortiz-Mantilla, Silvia; Makris, Nikos; Gregas, Matt; Bacic, Janine; Haehn, Daniel; Kennedy, David; Pienaar, Rudolph; Caviness, Verne S; Benasich, April A; Grant, P Ellen

    2013-09-01

    Elucidation of infant brain development is a critically important goal given the enduring impact of these early processes on various domains including later cognition and language. Although infants' whole-brain growth rates have long been available, regional growth rates have not been reported systematically. Accordingly, relatively less is known about the dynamics and organization of typically developing infant brains. Here we report global and regional volumetric growth of cerebrum, cerebellum, and brainstem with gender dimorphism, in 33 cross-sectional scans, over 3 to 13 months, using T1-weighted 3-dimensional spoiled gradient echo images and detailed semi-automated brain segmentation. Except for the midbrain and lateral ventricles, all absolute volumes of brain regions showed significant growth, with 6 different patterns of volumetric change. When normalized to the whole brain, the regional increase was characterized by 5 differential patterns. The putamen, cerebellar hemispheres, and total cerebellum were the only regions that showed positive growth in the normalized brain. Our results show region-specific patterns of volumetric change and contribute to the systematic understanding of infant brain development. This study greatly expands our knowledge of normal development and in future may provide a basis for identifying early deviation above and beyond normative variation that might signal higher risk for neurological disorders.

  16. An age estimation method using brain local features for T1-weighted images.

    Science.gov (United States)

    Kondo, Chihiro; Ito, Koichi; Kai Wu; Sato, Kazunori; Taki, Yasuyuki; Fukuda, Hiroshi; Aoki, Takafumi

    2015-08-01

    Previous statistical analysis studies using large-scale brain magnetic resonance (MR) image databases have examined that brain tissues have age-related morphological changes. This fact indicates that one can estimate the age of a subject from his/her brain MR image by evaluating morphological changes with healthy aging. This paper proposes an age estimation method using local features extracted from T1-weighted MR images. The brain local features are defined by volumes of brain tissues parcellated into local regions defined by the automated anatomical labeling atlas. The proposed method selects optimal local regions to improve the performance of age estimation. We evaluate performance of the proposed method using 1,146 T1-weighted images from a Japanese MR image database. We also discuss the medical implication of selected optimal local regions.

  17. Regional differences in brain glucose metabolism determined by imaging mass spectrometry

    OpenAIRE

    André Kleinridders; Heather A. Ferris; Michelle L. Reyzer; Michaela Rath; Marion Soto; M. Lisa Manier; Jeffrey Spraggins; Zhihong Yang; Robert C. Stanton; Richard M. Caprioli; C. Ronald Kahn

    2018-01-01

    Objective: Glucose is the major energy substrate of the brain and crucial for normal brain function. In diabetes, the brain is subject to episodes of hypo- and hyperglycemia resulting in acute outcomes ranging from confusion to seizures, while chronic metabolic dysregulation puts patients at increased risk for depression and Alzheimer's disease. In the present study, we aimed to determine how glucose is metabolized in different regions of the brain using imaging mass spectrometry (IMS). Metho...

  18. Hierarchical clustering into groups of human brain regions according to elemental composition

    International Nuclear Information System (INIS)

    Stedman, J.D.; Spyrou, N.M.

    1998-01-01

    Thirteen brain regions were dissected from both hemispheres of fifteen 'normal' ageing subjects (8 females, 7 males) of mean age 79±7 years. Elemental compositions were determined by simultaneous application of particle induced X-ray emission (PIXE) and Rutherford backscattering (RBS) analyses using a 2 MeV, 4 nA proton beam scanned over 4 mm 2 of the sample surface. Elemental concentrations were found to be dependent upon the brain region and hemisphere studied. Hierarchical cluster analysis was applied to group the brain regions according to the sample concentrations of eight elements. The resulting dendrogram is presented and its clusters related to the sample compositions of grey and white matter. (author)

  19. Functional photoacoustic imaging to observe regional brain activation induced by cocaine hydrochloride

    Science.gov (United States)

    Jo, Janggun; Yang, Xinmai

    2011-09-01

    Photoacoustic microscopy (PAM) was used to detect small animal brain activation in response to drug abuse. Cocaine hydrochloride in saline solution was injected into the blood stream of Sprague Dawley rats through tail veins. The rat brain functional change in response to the injection of drug was then monitored by the PAM technique. Images in the coronal view of the rat brain at the locations of 1.2 and 3.4 mm posterior to bregma were obtained. The resulted photoacoustic (PA) images showed the regional changes in the blood volume. Additionally, the regional changes in blood oxygenation were also presented. The results demonstrated that PA imaging is capable of monitoring regional hemodynamic changes induced by drug abuse.

  20. Global and regional annual brain volume loss rates in physiological aging.

    Science.gov (United States)

    Schippling, Sven; Ostwaldt, Ann-Christin; Suppa, Per; Spies, Lothar; Manogaran, Praveena; Gocke, Carola; Huppertz, Hans-Jürgen; Opfer, Roland

    2017-03-01

    The objective is to estimate average global and regional percentage brain volume loss per year (BVL/year) of the physiologically ageing brain. Two independent, cross-sectional single scanner cohorts of healthy subjects were included. The first cohort (n = 248) was acquired at the Medical Prevention Center (MPCH) in Hamburg, Germany. The second cohort (n = 316) was taken from the Open Access Series of Imaging Studies (OASIS). Brain parenchyma (BP), grey matter (GM), white matter (WM), corpus callosum (CC), and thalamus volumes were calculated. A non-parametric technique was applied to fit the resulting age-volume data. For each age, the BVL/year was derived from the age-volume curves. The resulting BVL/year curves were compared between the two cohorts. For the MPCH cohort, the BVL/year curve of the BP was an increasing function starting from 0.20% at the age of 35 years increasing to 0.52% at 70 years (corresponding values for GM ranged from 0.32 to 0.55%, WM from 0.02 to 0.47%, CC from 0.07 to 0.48%, and thalamus from 0.25 to 0.54%). Mean absolute difference between BVL/year trajectories across the age range of 35-70 years was 0.02% for BP, 0.04% for GM, 0.04% for WM, 0.11% for CC, and 0.02% for the thalamus. Physiological BVL/year rates were remarkably consistent between the two cohorts and independent from the scanner applied. Average BVL/year was clearly age and compartment dependent. These results need to be taken into account when defining cut-off values for pathological annual brain volume loss in disease models, such as multiple sclerosis.

  1. A probabilistic approach to delineating functional brain regions

    DEFF Research Database (Denmark)

    Kalbitzer, Jan; Svarer, Claus; Frokjaer, Vibe G

    2009-01-01

    The purpose of this study was to develop a reliable observer-independent approach to delineating volumes of interest (VOIs) for functional brain regions that are not identifiable on structural MR images. The case is made for the raphe nuclei, a collection of nuclei situated in the brain stem known...... to be densely packed with serotonin transporters (5-hydroxytryptaminic [5-HTT] system). METHODS: A template set for the raphe nuclei, based on their high content of 5-HTT as visualized in parametric (11)C-labeled 3-amino-4-(2-dimethylaminomethyl-phenylsulfanyl)-benzonitrile PET images, was created for 10...... healthy subjects. The templates were subsequently included in the region sets used in a previously published automatic MRI-based approach to create an observer- and activity-independent probabilistic VOI map. The probabilistic map approach was tested in a different group of 10 subjects and compared...

  2. Differential susceptibility of brain regions to tributyltin chloride toxicity.

    Science.gov (United States)

    Mitra, Sumonto; Siddiqui, Waseem A; Khandelwal, Shashi

    2015-12-01

    Tributyltin (TBT), a well-known endocrine disruptor, is an omnipresent environmental pollutant and is explicitly used in many industrial applications. Previously we have shown its neurotoxic potential on cerebral cortex of male Wistar rats. As the effect of TBT on other brain regions is not known, we planned this study to evaluate its effect on four brain regions (cerebellum, hippocampus, hypothalamus, and striatum). Four-week-old male Wistar rats were gavaged with a single dose of TBT-chloride (TBTC) (10, 20, and 30 mg/kg) and sacrificed on days 3 and 7, respectively. Effect of TBTC on blood-brain barrier (BBB) permeability and tin (Sn) accumulation were measured. Oxidative stress indexes such as reactive oxygen species (ROS), reduced and oxidized glutathione (GSH/GSSG) ratio, lipid peroxidation, and protein carbonylation were analyzed as they play an imperative role in various neuropathological conditions. Since metal catalyzed reactions are a major source of oxidant generation, levels of essential metals like iron (Fe), zinc (Zn), and calcium (Ca) were estimated. We found that TBTC disrupted BBB and increased Sn accumulation, both of which appear significantly correlated. Altered metal homeostasis and ROS generation accompanied by elevated lipid peroxidation and protein carbonylation indicated oxidative damage which appeared more pronounced in the striatum than in cerebellum, hippocampus, and hypothalamus. This could be associated to the depleted GSH levels in striatum. These results suggest that striatum is more susceptible to TBTC induced oxidative damage as compared with other brain regions under study. © 2014 Wiley Periodicals, Inc.

  3. Regional cerebral blood flow measurement in brain tumors

    International Nuclear Information System (INIS)

    Izunaga, Hiroshi; Hirota, Yoshihisa; Takahashi, Mutsumasa; Fuwa, Isao; Kodama, Takafumi; Matsukado, Yasuhiko

    1986-01-01

    The regional cerebral blood flow (CBF) was determined on seventeen patients with brain tumors. Ring type single photon emission CT (SPECT) was used following intravenous injection of 133 Xe. Case materials included eleven meningiomas and six malignant gliomas. Evaluation was performed with emphasis on the following points; 1. Correlation of the flow data within tumors to the angiographic tumor stains, 2. Influence of tumors on the cerebral blood flow of the normal brain tissue, 3. Correlation between degree of peripheral edema and the flow data of the affected hemispheres. There was significant correlation between flow data within tumors and angiographic tumor stains in meningiomas. Influence of tumors on cerebral blood flow of the normal tissue was greater in meningiomas than in gliomas. There was negative correlation between the degree of peripheral edema and the flow data of the affected hemisphere. It has been concluded that the measurement of CBF in brain tumors is a valuable method in evaluation of brain tumors. (author)

  4. Regional cerebral blood flow measurement in brain tumors

    Energy Technology Data Exchange (ETDEWEB)

    Izunaga, Hiroshi; Hirota, Yoshihisa; Takahashi, Mutsumasa; Fuwa, Isao; Kodama, Takafumi; Matsukado, Yasuhiko

    1986-10-01

    The regional cerebral blood flow (CBF) was determined on seventeen patients with brain tumors. Ring type single photon emission CT (SPECT) was used following intravenous injection of /sup 133/Xe. Case materials included eleven meningiomas and six malignant gliomas. Evaluation was performed with emphasis on the following points; 1. Correlation of the flow data within tumors to the angiographic tumor stains, 2. Influence of tumors on the cerebral blood flow of the normal brain tissue, 3. Correlation between degree of peripheral edema and the flow data of the affected hemispheres. There was significant correlation between flow data within tumors and angiographic tumor stains in meningiomas. Influence of tumors on cerebral blood flow of the normal tissue was greater in meningiomas than in gliomas. There was negative correlation between the degree of peripheral edema and the flow data of the affected hemisphere. It has been concluded that the measurement of CBF in brain tumors is a valuable method in evaluation of brain tumors.

  5. Moral values are associated with individual differences in regional brain volume.

    Science.gov (United States)

    Lewis, Gary J; Kanai, Ryota; Bates, Timothy C; Rees, Geraint

    2012-08-01

    Moral sentiment has been hypothesized to reflect evolved adaptations to social living. If so, individual differences in moral values may relate to regional variation in brain structure. We tested this hypothesis in a sample of 70 young, healthy adults examining whether differences on two major dimensions of moral values were significantly associated with regional gray matter volume. The two clusters of moral values assessed were "individualizing" (values of harm/care and fairness) and "binding" (deference to authority, in-group loyalty, and purity/sanctity). Individualizing was positively associated with left dorsomedial pFC volume and negatively associated with bilateral precuneus volume. For binding, a significant positive association was found for bilateral subcallosal gyrus and a trend to significance for the left anterior insula volume. These findings demonstrate that variation in moral sentiment reflects individual differences in brain structure and suggest a biological basis for moral sentiment, distributed across multiple brain regions.

  6. Brain functional network connectivity based on a visual task: visual information processing-related brain regions are significantly activated in the task state

    Directory of Open Access Journals (Sweden)

    Yan-li Yang

    2015-01-01

    Full Text Available It is not clear whether the method used in functional brain-network related research can be applied to explore the feature binding mechanism of visual perception. In this study, we investigated feature binding of color and shape in visual perception. Functional magnetic resonance imaging data were collected from 38 healthy volunteers at rest and while performing a visual perception task to construct brain networks active during resting and task states. Results showed that brain regions involved in visual information processing were obviously activated during the task. The components were partitioned using a greedy algorithm, indicating the visual network existed during the resting state. Z-values in the vision-related brain regions were calculated, confirming the dynamic balance of the brain network. Connectivity between brain regions was determined, and the result showed that occipital and lingual gyri were stable brain regions in the visual system network, the parietal lobe played a very important role in the binding process of color features and shape features, and the fusiform and inferior temporal gyri were crucial for processing color and shape information. Experimental findings indicate that understanding visual feature binding and cognitive processes will help establish computational models of vision, improve image recognition technology, and provide a new theoretical mechanism for feature binding in visual perception.

  7. Attentional Performance is Correlated with the Local Regional Efficiency of Intrinsic Brain Networks

    Directory of Open Access Journals (Sweden)

    Junhai eXu

    2015-07-01

    Full Text Available Attention is a crucial brain function for human beings. Using neuropsychological paradigms and task-based functional brain imaging, previous studies have indicated that widely distributed brain regions are engaged in three distinct attention subsystems: alerting, orienting and executive control (EC. Here, we explored the potential contribution of spontaneous brain activity to attention by examining whether resting-state activity could account for individual differences of the attentional performance in normal individuals. The resting-state functional images and behavioral data from attention network test (ANT task were collected in 59 healthy subjects. Graph analysis was conducted to obtain the characteristics of functional brain networks and linear regression analyses were used to explore their relationships with behavioral performances of the three attentional components. We found that there was no significant relationship between the attentional performance and the global measures, while the attentional performance was associated with specific local regional efficiency. These regions related to the scores of alerting, orienting and EC largely overlapped with the regions activated in previous task-related functional imaging studies, and were consistent with the intrinsic dorsal and ventral attention networks (DAN/VAN. In addition, the strong associations between the attentional performance and specific regional efficiency suggested that there was a possible relationship between the DAN/VAN and task performances in the ANT. We concluded that the intrinsic activity of the human brain could reflect the processing efficiency of the attention system. Our findings revealed a robust evidence for the functional significance of the efficiently organized intrinsic brain network for highly productive cognitions and the hypothesized role of the DAN/ VAN at rest.

  8. Altered regional homogeneity of spontaneous brain activity in idiopathic trigeminal neuralgia.

    Science.gov (United States)

    Wang, Yanping; Zhang, Xiaoling; Guan, Qiaobing; Wan, Lihong; Yi, Yahui; Liu, Chun-Feng

    2015-01-01

    The pathophysiology of idiopathic trigeminal neuralgia (ITN) has conventionally been thought to be induced by neurovascular compression theory. Recent structural brain imaging evidence has suggested an additional central component for ITN pathophysiology. However, far less attention has been given to investigations of the basis of abnormal resting-state brain activity in these patients. The objective of this study was to investigate local brain activity in patients with ITN and its correlation with clinical variables of pain. Resting-state functional magnetic resonance imaging data from 17 patients with ITN and 19 age- and sex-matched healthy controls were analyzed using regional homogeneity (ReHo) analysis, which is a data-driven approach used to measure the regional synchronization of spontaneous brain activity. Patients with ITN had decreased ReHo in the left amygdala, right parahippocampal gyrus, and left cerebellum and increased ReHo in the right inferior temporal gyrus, right thalamus, right inferior parietal lobule, and left postcentral gyrus (corrected). Furthermore, the increase in ReHo in the left precentral gyrus was positively correlated with visual analog scale (r=0.54; P=0.002). Our study found abnormal functional homogeneity of intrinsic brain activity in several regions in ITN, suggesting the maladaptivity of the process of daily pain attacks and a central role for the pathophysiology of ITN.

  9. Regional homogeneity of resting-state brain abnormalities in bipolar and unipolar depression.

    Science.gov (United States)

    Liu, Chun-Hong; Ma, Xin; Wu, Xia; Zhang, Yu; Zhou, Fu-Chun; Li, Feng; Tie, Chang-Le; Dong, Jie; Wang, Yong-Jun; Yang, Zhi; Wang, Chuan-Yue

    2013-03-05

    Bipolar disorder patients experiencing a depressive episode (BD-dep) without an observed history of mania are often misdiagnosed and are consequently treated as having unipolar depression (UD), leading to inadequate treatment and poor outcomes. An essential solution to this problem is to identify objective biological markers that distinguish BD-dep and UD patients at an early stage. However, studies directly comparing the brain dysfunctions associated with BD-dep and UD are rare. More importantly, the specificity of the differences in brain activity between these mental disorders has not been examined. With whole-brain regional homogeneity analysis and region-of-interest (ROI) based receiver operating characteristic (ROC) analysis, we aimed to compare the resting-state brain activity of BD-dep and UD patients. Furthermore, we examined the specific differences and whether these differences were attributed to the brain abnormality caused by BD-dep, UD, or both. Twenty-one bipolar and 21 unipolar depressed patients, as well as 26 healthy subjects matched for gender, age, and educational levels, participated in the study. We compared the differences in the regional homogeneity (ReHo) of the BD-dep and UD groups and further identified their pathophysiological abnormality. In the brain regions showing a difference between the BD-dep and UD groups, we further conducted receptive operation characteristic (ROC) analyses to confirm the effectiveness of the identified difference in classifying the patients. We observed ReHo differences between the BD-dep and UD groups in the right ventrolateral middle frontal gyrus, right dorsal anterior insular, right ventral anterior insular, right cerebellum posterior gyrus, right posterior cingulate cortex, right parahippocampal gyrus, and left cerebellum anterior gyrus. Further ROI comparisons and ROC analysis on these ROIs showed that the right parahippocampal gyrus reflected abnormality specific to the BD-dep group, while the right

  10. Digital assessment of distrurbances of ventilation distribution by defined regions of interest

    International Nuclear Information System (INIS)

    Reuter, T.D.; Kirchhuebel, H.; Dahlgruen, H.D.

    1976-01-01

    Pulmonary distribution of ventilation was assessed in ten patients with COPD on the basis of defined regions of interest. Areas of hypeventilation are demarcated on the basis of the trapped air scintigram corrected for lung volume. After the demarcations are transfered to the scintigram of fractional exchange of air the regional VI is computed and compared with normal values. The detectability of regional ventilation disturbances was found to be improved compared to a subdivision scheme of six regions of interest

  11. Regional brain gray and white matter changes in perinatally HIV-infected adolescents☆

    Science.gov (United States)

    Sarma, Manoj K.; Nagarajan, Rajakumar; Keller, Margaret A.; Kumar, Rajesh; Nielsen-Saines, Karin; Michalik, David E.; Deville, Jaime; Church, Joseph A.; Thomas, M. Albert

    2013-01-01

    Despite the success of antiretroviral therapy (ART), perinatally infected HIV remains a major health problem worldwide. Although advance neuroimaging studies have investigated structural brain changes in HIV-infected adults, regional gray matter (GM) and white matter (WM) volume changes have not been reported in perinatally HIV-infected adolescents and young adults. In this cross-sectional study, we investigated regional GM and WM changes in 16 HIV-infected youths receiving ART (age 17.0 ± 2.9 years) compared with age-matched 14 healthy controls (age 16.3 ± 2.3 years) using magnetic resonance imaging (MRI)-based high-resolution T1-weighted images with voxel based morphometry (VBM) analyses. White matter atrophy appeared in perinatally HIV-infected youths in brain areas including the bilateral posterior corpus callosum (CC), bilateral external capsule, bilateral ventral temporal WM, mid cerebral peduncles, and basal pons over controls. Gray matter volume increase was observed in HIV-infected youths for several regions including the left superior frontal gyrus, inferior occipital gyrus, gyrus rectus, right mid cingulum, parahippocampal gyrus, bilateral inferior temporal gyrus, and middle temporal gyrus compared with controls. Global WM and GM volumes did not differ significantly between groups. These results indicate WM injury in perinatally HIV-infected youths, but the interpretation of the GM results, which appeared as increased regional volumes, is not clear. Further longitudinal studies are needed to clarify if our results represent active ongoing brain infection or toxicity from HIV treatment resulting in neuronal cell swelling and regional increased GM volume. Our findings suggest that assessment of regional GM and WM volume changes, based on VBM procedures, may be an additional measure to assess brain integrity in HIV-infected youths and to evaluate success of current ART therapy for efficacy in the brain. PMID:24380059

  12. Regional brain gray and white matter changes in perinatally HIV-infected adolescents

    Directory of Open Access Journals (Sweden)

    Manoj K. Sarma

    2014-01-01

    Full Text Available Despite the success of antiretroviral therapy (ART, perinatally infected HIV remains a major health problem worldwide. Although advance neuroimaging studies have investigated structural brain changes in HIV-infected adults, regional gray matter (GM and white matter (WM volume changes have not been reported in perinatally HIV-infected adolescents and young adults. In this cross-sectional study, we investigated regional GM and WM changes in 16 HIV-infected youths receiving ART (age 17.0 ± 2.9 years compared with age-matched 14 healthy controls (age 16.3 ± 2.3 years using magnetic resonance imaging (MRI-based high-resolution T1-weighted images with voxel based morphometry (VBM analyses. White matter atrophy appeared in perinatally HIV-infected youths in brain areas including the bilateral posterior corpus callosum (CC, bilateral external capsule, bilateral ventral temporal WM, mid cerebral peduncles, and basal pons over controls. Gray matter volume increase was observed in HIV-infected youths for several regions including the left superior frontal gyrus, inferior occipital gyrus, gyrus rectus, right mid cingulum, parahippocampal gyrus, bilateral inferior temporal gyrus, and middle temporal gyrus compared with controls. Global WM and GM volumes did not differ significantly between groups. These results indicate WM injury in perinatally HIV-infected youths, but the interpretation of the GM results, which appeared as increased regional volumes, is not clear. Further longitudinal studies are needed to clarify if our results represent active ongoing brain infection or toxicity from HIV treatment resulting in neuronal cell swelling and regional increased GM volume. Our findings suggest that assessment of regional GM and WM volume changes, based on VBM procedures, may be an additional measure to assess brain integrity in HIV-infected youths and to evaluate success of current ART therapy for efficacy in the brain.

  13. Identification of a set of genes showing regionally enriched expression in the mouse brain

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    Marra Marco A

    2008-07-01

    Full Text Available Abstract Background The Pleiades Promoter Project aims to improve gene therapy by designing human mini-promoters ( Results We have utilized LongSAGE to identify regionally enriched transcripts in the adult mouse brain. As supplemental strategies, we also performed a meta-analysis of published literature and inspected the Allen Brain Atlas in situ hybridization data. From a set of approximately 30,000 mouse genes, 237 were identified as showing specific or enriched expression in 30 target regions of the mouse brain. GO term over-representation among these genes revealed co-involvement in various aspects of central nervous system development and physiology. Conclusion Using a multi-faceted expression validation approach, we have identified mouse genes whose human orthologs are good candidates for design of mini-promoters. These mouse genes represent molecular markers in several discrete brain regions/cell-types, which could potentially provide a mechanistic explanation of unique functions performed by each region. This set of markers may also serve as a resource for further studies of gene regulatory elements influencing brain expression.

  14. Brain Region-Specific Activity Patterns after Recent or Remote Memory Retrieval of Auditory Conditioned Fear

    Science.gov (United States)

    Kwon, Jeong-Tae; Jhang, Jinho; Kim, Hyung-Su; Lee, Sujin; Han, Jin-Hee

    2012-01-01

    Memory is thought to be sparsely encoded throughout multiple brain regions forming unique memory trace. Although evidence has established that the amygdala is a key brain site for memory storage and retrieval of auditory conditioned fear memory, it remains elusive whether the auditory brain regions may be involved in fear memory storage or…

  15. Cognitive control of drug craving inhibits brain reward regions in cocaine abusers

    International Nuclear Information System (INIS)

    Volkow, N.D.; Fowler, J.; Wang, G.J.; Telang, F.; Logan, J.; Jayne, M.; Ma, Y.; Pradhan, K.; Wong, C.T.; Swanson, J.M.

    2010-01-01

    Loss of control over drug taking is considered a hallmark of addiction and is critical in relapse. Dysfunction of frontal brain regions involved with inhibitory control may underlie this behavior. We evaluated whether addicted subjects when instructed to purposefully control their craving responses to drug-conditioned stimuli can inhibit limbic brain regions implicated in drug craving. We used PET and 2-deoxy-2[18F]fluoro-D-glucose to measure brain glucose metabolism (marker of brain function) in 24 cocaine abusers who watched a cocaine-cue video and compared brain activation with and without instructions to cognitively inhibit craving. A third scan was obtained at baseline (without video). Statistical parametric mapping was used for analysis and corroborated with regions of interest. The cocaine-cue video increased craving during the no-inhibition condition (pre 3 ± 3, post 6 ± 3; p < 0.001) but not when subjects were instructed to inhibit craving (pre 3 ± 2, post 3 ± 3). Comparisons with baseline showed visual activation for both cocaine-cue conditions and limbic inhibition (accumbens, orbitofrontal, insula, cingulate) when subjects purposefully inhibited craving (p < 0.001). Comparison between cocaine-cue conditions showed lower metabolism with cognitive inhibition in right orbitofrontal cortex and right accumbens (p < 0.005), which was associated with right inferior frontal activation (r = -0.62, p < 0.005). Decreases in metabolism in brain regions that process the predictive (nucleus accumbens) and motivational value (orbitofrontal cortex) of drug-conditioned stimuli were elicited by instruction to inhibit cue-induced craving. This suggests that cocaine abusers may retain some ability to inhibit craving and that strengthening fronto-accumbal regulation may be therapeutically beneficial in addiction.

  16. Cognitive control of drug craving inhibits brain reward regions in cocaine abusers

    Energy Technology Data Exchange (ETDEWEB)

    Volkow, N.D.; Fowler, J.; Wang, G.J.; Telang, F.; Logan, J.; Jayne, M.; Ma, Y.; Pradhan, K.; Wong, C.T.; Swanson, J.M.

    2010-01-01

    Loss of control over drug taking is considered a hallmark of addiction and is critical in relapse. Dysfunction of frontal brain regions involved with inhibitory control may underlie this behavior. We evaluated whether addicted subjects when instructed to purposefully control their craving responses to drug-conditioned stimuli can inhibit limbic brain regions implicated in drug craving. We used PET and 2-deoxy-2[18F]fluoro-D-glucose to measure brain glucose metabolism (marker of brain function) in 24 cocaine abusers who watched a cocaine-cue video and compared brain activation with and without instructions to cognitively inhibit craving. A third scan was obtained at baseline (without video). Statistical parametric mapping was used for analysis and corroborated with regions of interest. The cocaine-cue video increased craving during the no-inhibition condition (pre 3 {+-} 3, post 6 {+-} 3; p < 0.001) but not when subjects were instructed to inhibit craving (pre 3 {+-} 2, post 3 {+-} 3). Comparisons with baseline showed visual activation for both cocaine-cue conditions and limbic inhibition (accumbens, orbitofrontal, insula, cingulate) when subjects purposefully inhibited craving (p < 0.001). Comparison between cocaine-cue conditions showed lower metabolism with cognitive inhibition in right orbitofrontal cortex and right accumbens (p < 0.005), which was associated with right inferior frontal activation (r = -0.62, p < 0.005). Decreases in metabolism in brain regions that process the predictive (nucleus accumbens) and motivational value (orbitofrontal cortex) of drug-conditioned stimuli were elicited by instruction to inhibit cue-induced craving. This suggests that cocaine abusers may retain some ability to inhibit craving and that strengthening fronto-accumbal regulation may be therapeutically beneficial in addiction.

  17. Regional magnetic resonance spectroscopy of the brain in autistic individuals

    International Nuclear Information System (INIS)

    Hisaoka, S.; Harada, M.; Nishitani, H.; Mori, K.

    2001-01-01

    We studied the variations in the concentration of metabolites with brain region and age in autistic individuals and normal controls using multiple analysis of covariance. We examined 55 autistic individuals (2-21 years old, 47 male and eight female) and 51 normal children (3 months-15 years old, 26 boys and 25 girls). Single volumes of interest were placed in the frontal, parietal and temporal region on both sides, the brain stem and cingulate gyrus. The concentration of each metabolite was quantified by the water reference method. The concentration of N-acetylaspartate in the temporal regions (Brodmann's areas 41 and 42) in the autistic individuals were significantly lower than those in the controls (P < 0.05), but concentrations in other regions were not significantly different between the autistic individuals and controls. This suggests low density or dysfunction of neurones in Brodmann's areas 41 and 42 in autistic individual, which might be related to the disturbances of the sensory speech centre (Wernicke's area) in autism. (orig.)

  18. Regional magnetic resonance spectroscopy of the brain in autistic individuals

    Energy Technology Data Exchange (ETDEWEB)

    Hisaoka, S; Harada, M; Nishitani, H [Dept. of Radiology, School of Medicine, University of Tokushima (Japan); Mori, K [Dept. of Paediatrics, School of Medicine, University of Tokushima (Japan)

    2001-06-01

    We studied the variations in the concentration of metabolites with brain region and age in autistic individuals and normal controls using multiple analysis of covariance. We examined 55 autistic individuals (2-21 years old, 47 male and eight female) and 51 normal children (3 months-15 years old, 26 boys and 25 girls). Single volumes of interest were placed in the frontal, parietal and temporal region on both sides, the brain stem and cingulate gyrus. The concentration of each metabolite was quantified by the water reference method. The concentration of N-acetylaspartate in the temporal regions (Brodmann's areas 41 and 42) in the autistic individuals were significantly lower than those in the controls (P < 0.05), but concentrations in other regions were not significantly different between the autistic individuals and controls. This suggests low density or dysfunction of neurones in Brodmann's areas 41 and 42 in autistic individual, which might be related to the disturbances of the sensory speech centre (Wernicke's area) in autism. (orig.)

  19. Region based Brain Computer Interface for a home control application.

    Science.gov (United States)

    Akman Aydin, Eda; Bay, Omer Faruk; Guler, Inan

    2015-08-01

    Environment control is one of the important challenges for disabled people who suffer from neuromuscular diseases. Brain Computer Interface (BCI) provides a communication channel between the human brain and the environment without requiring any muscular activation. The most important expectation for a home control application is high accuracy and reliable control. Region-based paradigm is a stimulus paradigm based on oddball principle and requires selection of a target at two levels. This paper presents an application of region based paradigm for a smart home control application for people with neuromuscular diseases. In this study, a region based stimulus interface containing 49 commands was designed. Five non-disabled subjects were attended to the experiments. Offline analysis results of the experiments yielded 95% accuracy for five flashes. This result showed that region based paradigm can be used to select commands of a smart home control application with high accuracy in the low number of repetitions successfully. Furthermore, a statistically significant difference was not observed between the level accuracies.

  20. Positron-emission tomography of brain regions activated by recognition of familiar music.

    Science.gov (United States)

    Satoh, M; Takeda, K; Nagata, K; Shimosegawa, E; Kuzuhara, S

    2006-05-01

    We can easily recognize familiar music by listening to only one or 2 of its opening bars, but the brain regions that participate in this cognitive processing remain undetermined. We used positron-emission tomography (PET) to study changes in regional cerebral blood flow (rCBF) that occur during listening to familiar music. We used a PET subtraction technique to elucidate the brain regions associated with the recognition of familiar melodies such as well-known nursery tunes. Nonmusicians performed 2 kinds of musical tasks: judging the familiarity of musical pieces (familiarity task) and detecting deliberately altered notes in the pieces (alteration-detecting task). During the familiarity task, bilateral anterior portions of bilateral temporal lobes, superior temporal regions, and parahippocampal gyri were activated. The alteration-detecting task bilaterally activated regions in the precunei, superior/inferior parietal lobules, and lateral surface of frontal lobes, which seemed to show a correlation with the analysis of music. We hypothesize that during the familiarity task, activated brain regions participate in retrieval from long-term memory and verbal and emotional processing of familiar melodies. Our results reinforced the hypothesis reported in the literature as a result of group and case studies, that temporal lobe regions participate in the recognition of familiar melodies.

  1. Somatic DNA recombination yielding circular DNA and deletion of a genomic region in embryonic brain

    International Nuclear Information System (INIS)

    Maeda, Toyoki; Chijiiwa, Yoshiharu; Tsuji, Hideo; Sakoda, Saburo; Tani, Kenzaburo; Suzuki, Tomokazu

    2004-01-01

    In this study, a mouse genomic region is identified that undergoes DNA rearrangement and yields circular DNA in brain during embryogenesis. External region-directed inverse polymerase chain reaction on circular DNA extracted from late embryonic brain tissue repeatedly detected DNA of this region containing recombination joints. Wide-range genomic PCR and digestion-circularization PCR analysis showed this region underwent recombination accompanied with deletion of intervening sequences, including the circularized regions. This region was mapped by fluorescence in situ hybridization to C1 on mouse chromosome 16, where no gene and no physiological DNA rearrangement had been identified. DNA sequence in the region has segmental homology to an orthologous region on human chromosome 3q.13. These observations demonstrated somatic DNA recombination yielding genomic deletions in brain during embryogenesis

  2. Relationship between plasma analytes and SPARE-AD defined brain atrophy patterns in ADNI.

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    Jon B Toledo

    Full Text Available Different inflammatory and metabolic pathways have been associated with Alzheimeŕs disease (AD. However, only recently multi-analyte panels to study a large number of molecules in well characterized cohorts have been made available. These panels could help identify molecules that point to the affected pathways. We studied the relationship between a panel of plasma biomarkers (Human DiscoveryMAP and presence of AD-like brain atrophy patterns defined by a previously published index (SPARE-AD at baseline in subjects of the ADNI cohort. 818 subjects had MRI-derived SPARE-AD scores, of these subjects 69% had plasma biomarkers and 51% had CSF tau and Aβ measurements. Significant analyte-SPARE-AD and analytes correlations were studied in adjusted models. Plasma cortisol and chromogranin A showed a significant association that did not remain significant in the CSF signature adjusted model. Plasma macrophage inhibitory protein-1α and insulin-like growth factor binding protein 2 showed a significant association with brain atrophy in the adjusted model. Cortisol levels showed an inverse association with tests measuring processing speed. Our results indicate that stress and insulin responses and cytokines associated with recruitment of inflammatory cells in MCI-AD are associated with its characteristic AD-like brain atrophy pattern and correlate with clinical changes or CSF biomarkers.

  3. On the blood-brain barrier to peptides: [3H]gonadotropin-releasing hormone accumulation by eighteen regions of the rat brain and by anterior pituitary

    International Nuclear Information System (INIS)

    Ermisch, A.; Ruehle, H.J.; Klauschenz, E.; Kretzschmar, R.

    1984-01-01

    After intracarotid injection of [ 3 H]gonadotropin-releasing hormone ([ 3 H]GnRH) the mean accumulation of radioactivity per unit wet weight of 18 brain samples investigated and the anterior pituitary was 0.38 +- 0.11% g -1 of the injected tracer dose. This indicates a low but measurable brain uptake of the peptide. The brain uptake of [ 3 H]GnRH in blood-brain barrier (BBB)-protected regions is 5% of that of separately investigated [ 3 H]OH. In BBB-free regions the accumulation of radioactivity was more than 25-fold higher than in BBB-protected regions. The accumulation of [ 3 H]GnRH among regions with BBB varies less than among regions with leaky endothelia. The data presented for [ 3 H]GnRH are similar to those for other peptides so far investigated. (author)

  4. Regional changes in brain 2-14C-deoxyglucose uptake induced by convulsant and non-convulsant doses of lindane

    International Nuclear Information System (INIS)

    Sanfeliu, C.; Sola, C.; Camon, L.; Martinez, E.; Rodriguez-Farre, E.

    1990-01-01

    Lindane-induced dose- and time-related changes in regional 2-14C-deoxyglucose (2-DG) uptake were examined in 59 discrete rat brain structures using the 2-DG autoradiographic technique. At different times (0.5-144 hr) after administration of a seizure-inducing single dose of lindane (60 mg/kg), 2-DG uptake was significantly increased in 18 cortical and subcortical regions mainly related to the limbic system (e.g., Ammon's horn, dentate gyrus, septal nuclei, nucleus accumbens, olfactory cortex) and extrapyramidal and sensory-motor areas (e.g., cerebellar cortex, red nucleus, medial vestibular nucleus). There was also a significant increase in superior colliculus layer II. In addition, significant decreases occurred in a group of 6 regions (e.g., auditory and motor cortices). Non-convulsing animals treated with the same dose of lindane showed a regional pattern of 2-DG uptake less modified than the convulsant group. A non-convulsant single dose of lindane (30 mg/kg) also modified significantly the 2-DG uptake (0.5-24 hr) in some brain areas. Although the various single doses of lindane tested produced different altered patterns of brain 2-DG uptake, some structures showed a similar trend in their modification (e.g., superior colliculi and accumbens, raphe and red nuclei). Repeated non-convulsant doses of lindane produced defined and long-lasting significant elevations of 2-DG uptake in some subcortical structures. Considering the treated groups all together, 2-DG uptake increased significantly in 26 of the 59 regions examined but only decreased significantly in 9 of them during the course of lindane effects. This fact can be related to the stimulant action described for this neurotoxic agent. The observed pattern provides a descriptive approach to the functional alterations occurring in vivo during the course of lindane intoxication

  5. Development of the brain's functional network architecture.

    Science.gov (United States)

    Vogel, Alecia C; Power, Jonathan D; Petersen, Steven E; Schlaggar, Bradley L

    2010-12-01

    A full understanding of the development of the brain's functional network architecture requires not only an understanding of developmental changes in neural processing in individual brain regions but also an understanding of changes in inter-regional interactions. Resting state functional connectivity MRI (rs-fcMRI) is increasingly being used to study functional interactions between brain regions in both adults and children. We briefly review methods used to study functional interactions and networks with rs-fcMRI and how these methods have been used to define developmental changes in network functional connectivity. The developmental rs-fcMRI studies to date have found two general properties. First, regional interactions change from being predominately anatomically local in children to interactions spanning longer cortical distances in young adults. Second, this developmental change in functional connectivity occurs, in general, via mechanisms of segregation of local regions and integration of distant regions into disparate subnetworks.

  6. Major Shifts in Glial Regional Identity Are a Transcriptional Hallmark of Human Brain Aging

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    Lilach Soreq

    2017-01-01

    Full Text Available Gene expression studies suggest that aging of the human brain is determined by a complex interplay of molecular events, although both its region- and cell-type-specific consequences remain poorly understood. Here, we extensively characterized aging-altered gene expression changes across ten human brain regions from 480 individuals ranging in age from 16 to 106 years. We show that astrocyte- and oligodendrocyte-specific genes, but not neuron-specific genes, shift their regional expression patterns upon aging, particularly in the hippocampus and substantia nigra, while the expression of microglia- and endothelial-specific genes increase in all brain regions. In line with these changes, high-resolution immunohistochemistry demonstrated decreased numbers of oligodendrocytes and of neuronal subpopulations in the aging brain cortex. Finally, glial-specific genes predict age with greater precision than neuron-specific genes, thus highlighting the need for greater mechanistic understanding of neuron-glia interactions in aging and late-life diseases.

  7. Major Shifts in Glial Regional Identity Are a Transcriptional Hallmark of Human Brain Aging.

    Science.gov (United States)

    Soreq, Lilach; Rose, Jamie; Soreq, Eyal; Hardy, John; Trabzuni, Daniah; Cookson, Mark R; Smith, Colin; Ryten, Mina; Patani, Rickie; Ule, Jernej

    2017-01-10

    Gene expression studies suggest that aging of the human brain is determined by a complex interplay of molecular events, although both its region- and cell-type-specific consequences remain poorly understood. Here, we extensively characterized aging-altered gene expression changes across ten human brain regions from 480 individuals ranging in age from 16 to 106 years. We show that astrocyte- and oligodendrocyte-specific genes, but not neuron-specific genes, shift their regional expression patterns upon aging, particularly in the hippocampus and substantia nigra, while the expression of microglia- and endothelial-specific genes increase in all brain regions. In line with these changes, high-resolution immunohistochemistry demonstrated decreased numbers of oligodendrocytes and of neuronal subpopulations in the aging brain cortex. Finally, glial-specific genes predict age with greater precision than neuron-specific genes, thus highlighting the need for greater mechanistic understanding of neuron-glia interactions in aging and late-life diseases. Copyright © 2017 The Author(s). Published by Elsevier Inc. All rights reserved.

  8. Region-Specific Defects of Respiratory Capacities in the Ndufs4(KO Mouse Brain.

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    Ernst-Bernhard Kayser

    Full Text Available Lack of NDUFS4, a subunit of mitochondrial complex I (NADH:ubiquinone oxidoreductase, causes Leigh syndrome (LS, a progressive encephalomyopathy. Knocking out Ndufs4, either systemically or in brain only, elicits LS in mice. In patients as well as in KO mice distinct regions of the brain degenerate while surrounding tissue survives despite systemic complex I dysfunction. For the understanding of disease etiology and ultimately for the development of rationale treatments for LS, it appears important to uncover the mechanisms that govern focal neurodegeneration.Here we used the Ndufs4(KO mouse to investigate whether regional and temporal differences in respiratory capacity of the brain could be correlated with neurodegeneration. In the KO the respiratory capacity of synaptosomes from the degeneration prone regions olfactory bulb, brainstem and cerebellum was significantly decreased. The difference was measurable even before the onset of neurological symptoms. Furthermore, neither compensating nor exacerbating changes in glycolytic capacity of the synaptosomes were found. By contrast, the KO retained near normal levels of synaptosomal respiration in the degeneration-resistant/resilient "rest" of the brain. We also investigated non-synaptic mitochondria. The KO expectedly had diminished capacity for oxidative phosphorylation (state 3 respiration with complex I dependent substrate combinations pyruvate/malate and glutamate/malate but surprisingly had normal activity with α-ketoglutarate/malate. No correlation between oxidative phosphorylation (pyruvate/malate driven state 3 respiration and neurodegeneration was found: Notably, state 3 remained constant in the KO while in controls it tended to increase with time leading to significant differences between the genotypes in older mice in both vulnerable and resilient brain regions. Neither regional ROS damage, measured as HNE-modified protein, nor regional complex I stability, assessed by blue native

  9. Automatic detection of the hippocampal region associated with Alzheimer's disease from microscopic images of mice brain

    Science.gov (United States)

    Albaidhani, Tahseen; Hawkes, Cheryl; Jassim, Sabah; Al-Assam, Hisham

    2016-05-01

    The hippocampus is the region of the brain that is primarily associated with memory and spatial navigation. It is one of the first brain regions to be damaged when a person suffers from Alzheimer's disease. Recent research in this field has focussed on the assessment of damage to different blood vessels within the hippocampal region from a high throughput brain microscopic images. The ultimate aim of our research is the creation of an automatic system to count and classify different blood vessels such as capillaries, veins, and arteries in the hippocampus region. This work should provide biologists with efficient and accurate tools in their investigation of the causes of Alzheimer's disease. Locating the boundary of the Region of Interest in the hippocampus from microscopic images of mice brain is the first essential stage towards developing such a system. This task benefits from the variation in colour channels and texture between the two sides of the hippocampus and the boundary region. Accordingly, the developed initial step of our research to locating the hippocampus edge uses a colour-based segmentation of the brain image followed by Hough transforms on the colour channel that isolate the hippocampus region. The output is then used to split the brain image into two sides of the detected section of the boundary: the inside region and the outside region. Experimental results on a sufficiently number of microscopic images demonstrate the effectiveness of the developed solution.

  10. Regional gray matter growth, sexual dimorphism, and cerebral asymmetry in the neonatal brain.

    Science.gov (United States)

    Gilmore, John H; Lin, Weili; Prastawa, Marcel W; Looney, Christopher B; Vetsa, Y Sampath K; Knickmeyer, Rebecca C; Evans, Dianne D; Smith, J Keith; Hamer, Robert M; Lieberman, Jeffrey A; Gerig, Guido

    2007-02-07

    Although there has been recent interest in the study of childhood and adolescent brain development, very little is known about normal brain development in the first few months of life. In older children, there are regional differences in cortical gray matter development, whereas cortical gray and white matter growth after birth has not been studied to a great extent. The adult human brain is also characterized by cerebral asymmetries and sexual dimorphisms, although very little is known about how these asymmetries and dimorphisms develop. We used magnetic resonance imaging and an automatic segmentation methodology to study brain structure in 74 neonates in the first few weeks after birth. We found robust cortical gray matter growth compared with white matter growth, with occipital regions growing much faster than prefrontal regions. Sexual dimorphism is present at birth, with males having larger total brain cortical gray and white matter volumes than females. In contrast to adults and older children, the left hemisphere is larger than the right hemisphere, and the normal pattern of fronto-occipital asymmetry described in older children and adults is not present. Regional differences in cortical gray matter growth are likely related to differential maturation of sensory and motor systems compared with prefrontal executive function after birth. These findings also indicate that whereas some adult patterns of sexual dimorphism and cerebral asymmetries are present at birth, others develop after birth.

  11. Altered regional homogeneity of spontaneous brain activity in idiopathic trigeminal neuralgia

    Directory of Open Access Journals (Sweden)

    Wang Y

    2015-10-01

    Full Text Available Yanping Wang,1,2 Xiaoling Zhang,2 Qiaobing Guan,2 Lihong Wan,2 Yahui Yi,2 Chun-Feng Liu1 1Department of Neurology, The Second Affiliated Hospital of Soochow University, Suzhou, Jiangsu Province, 2Department of Neurology, The Second Hospital of Jiaxing City, Jiaxing, Zhejiang Province, People’s Republic of China Abstract: The pathophysiology of idiopathic trigeminal neuralgia (ITN has conventionally been thought to be induced by neurovascular compression theory. Recent structural brain imaging evidence has suggested an additional central component for ITN pathophysiology. However, far less attention has been given to investigations of the basis of abnormal resting-state brain activity in these patients. The objective of this study was to investigate local brain activity in patients with ITN and its correlation with clinical variables of pain. Resting-state functional magnetic resonance imaging data from 17 patients with ITN and 19 age- and sex-matched healthy controls were analyzed using regional homogeneity (ReHo analysis, which is a data-driven approach used to measure the regional synchronization of spontaneous brain activity. Patients with ITN had decreased ReHo in the left amygdala, right parahippocampal gyrus, and left cerebellum and increased ReHo in the right inferior temporal gyrus, right thalamus, right inferior parietal lobule, and left postcentral gyrus (corrected. Furthermore, the increase in ReHo in the left precentral gyrus was positively correlated with visual analog scale (r=0.54; P=0.002. Our study found abnormal functional homogeneity of intrinsic brain activity in several regions in ITN, suggesting the maladaptivity of the process of daily pain attacks and a central role for the pathophysiology of ITN. Keywords: trigeminal neuralgia, resting fMRI, brain, chronic pain, local connectivity

  12. Expression of Tau Pathology-Related Proteins in Different Brain Regions: A Molecular Basis of Tau Pathogenesis.

    Science.gov (United States)

    Hu, Wen; Wu, Feng; Zhang, Yanchong; Gong, Cheng-Xin; Iqbal, Khalid; Liu, Fei

    2017-01-01

    Microtubule-associated protein tau is hyperphosphorylated and aggregated in affected neurons in Alzheimer disease (AD) brains. The tau pathology starts from the entorhinal cortex (EC), spreads to the hippocampus and frontal and temporal cortices, and finally to all isocortex areas, but the cerebellum is spared from tau lesions. The molecular basis of differential vulnerability of different brain regions to tau pathology is not understood. In the present study, we analyzed brain regional expressions of tau and tau pathology-related proteins. We found that tau was hyperphosphorylated at multiple sites in the frontal cortex (FC), but not in the cerebellum, from AD brain. The level of tau expression in the cerebellum was about 1/4 of that seen in the frontal and temporal cortices in human brain. In the rat brain, the expression level of tau with three microtubule-binding repeats (3R-tau) was comparable in the hippocampus, EC, FC, parietal-temporal cortex (PTC), occipital-temporal cortex (OTC), striatum, thalamus, olfactory bulb (OB) and cerebellum. However, the expression level of 4R-tau was the highest in the EC and the lowest in the cerebellum. Tau phosphatases, kinases, microtubule-related proteins and other tau pathology-related proteins were also expressed in a region-specific manner in the rat brain. These results suggest that higher levels of tau and tau kinases in the EC and low levels of these proteins in the cerebellum may accounts for the vulnerability and resistance of these representative brain regions to the development of tau pathology, respectively. The present study provides the regional expression profiles of tau and tau pathology-related proteins in the brain, which may help understand the brain regional vulnerability to tau pathology in neurodegenerative tauopathies.

  13. Time series analysis of brain regional volume by MR image

    International Nuclear Information System (INIS)

    Tanaka, Mika; Tarusawa, Ayaka; Nihei, Mitsuyo; Fukami, Tadanori; Yuasa, Tetsuya; Wu, Jin; Ishiwata, Kiichi; Ishii, Kenji

    2010-01-01

    The present study proposed a methodology of time series analysis of volumes of frontal, parietal, temporal and occipital lobes and cerebellum because such volumetric reports along the process of individual's aging have been scarcely presented. Subjects analyzed were brain images of 2 healthy males and 18 females of av. age of 69.0 y, of which T1-weighted 3D SPGR (spoiled gradient recalled in the steady state) acquisitions with a GE SIGNA EXCITE HD 1.5T machine were conducted for 4 times in the time series of 42-50 months. The image size was 256 x 256 x (86-124) voxels with digitization level 16 bits. As the template for the regions, the standard gray matter atlas (icbn452 a tlas p robability g ray) and its labeled one (icbn.Labels), provided by UCLA Laboratory of Neuro Imaging, were used for individual's standardization. Segmentation, normalization and coregistration were performed with the MR imaging software SPM8 (Statistic Parametric Mapping 8). Volumes of regions were calculated as their voxel ratio to the whole brain voxel in percent. It was found that the regional volumes decreased with aging in all above lobes examined and cerebellum in average percent per year of -0.11, -0.07, -0.04, -0.02, and -0.03, respectively. The procedure for calculation of the regional volumes, which has been manually operated hitherto, can be automatically conducted for the individual brain using the standard atlases above. (T.T.)

  14. Regional homogeneity of the resting-state brain activity correlates with individual intelligence.

    Science.gov (United States)

    Wang, Leiqiong; Song, Ming; Jiang, Tianzi; Zhang, Yunting; Yu, Chunshui

    2011-01-25

    Resting-state functional magnetic resonance imaging has confirmed that the strengths of the long distance functional connectivity between different brain areas are correlated with individual differences in intelligence. However, the association between the local connectivity within a specific brain region and intelligence during rest remains largely unknown. The aim of this study is to investigate the relationship between local connectivity and intelligence. Fifty-nine right-handed healthy adults participated in the study. The regional homogeneity (ReHo) was used to assess the strength of local connectivity. The associations between ReHo and full-scale intelligence quotient (FSIQ) scores were studied in a voxel-wise manner using partial correlation analysis controlling for age and sex. We found that the FSIQ scores were positively correlated with the ReHo values of the bilateral inferior parietal lobules, middle frontal, parahippocampal and inferior temporal gyri, the right thalamus, superior frontal and fusiform gyri, and the left superior parietal lobule. The main findings are consistent with the parieto-frontal integration theory (P-FIT) of intelligence, supporting the view that general intelligence involves multiple brain regions throughout the brain. Copyright © 2010 Elsevier Ireland Ltd. All rights reserved.

  15. Normal regional brain iron concentration in restless legs syndrome measured by MRI

    Directory of Open Access Journals (Sweden)

    Susanne Knake

    2009-12-01

    Full Text Available Susanne Knake1, Johannes T Heverhagen2, Katja Menzler1, Boris Keil2, Wolfgang H Oertel1, Karin Stiasny-Kolster11Department of Neurology, Center of Nervous Diseases, 2Department of Radiology, Philipps University, Marburg, GermanyAbstract: Using a T2* gradient echo magnetic resonance imaging (MRI sequence, regional T2 signal intensity (SI values, a surrogate marker for T2 values, were determined in 12 regions of interest (substantia nigra, pallidum, caudate head, thalamus, occipital white matter, and frontal white matter bilaterally and in two reference regions (cerebrospinal fluid and bone in 12 patients suffering from moderate to severe idiopathic restless legs syndrome (RLS; mean age 58.5 ± 8.7 years for 12.1 ± 9.1 years and in 12 healthy control subjects (mean age 56.8 ± 10.6 years. Iron deposits shorten T2 relaxation times on T2-weighted MRI. We used regional T2* SI to estimate regional T2-values. A T2-change ratio was calculated for each region of interest relative to the reference regions. We did not find significant differences in any of the investigated brain regions. In addition, serum measures involved in iron metabolism did not correlate with T2 SI values. We could not replicate earlier findings describing reduced regional brain iron concentrations in patients with RLS. Our results do not support the view of substantially impaired regional brain iron in RLS.Keywords: restless legs syndrome, pathophysiology, iron, MRI, substantia nigra

  16. A Method for Automatic Extracting Intracranial Region in MR Brain Image

    Science.gov (United States)

    Kurokawa, Keiji; Miura, Shin; Nishida, Makoto; Kageyama, Yoichi; Namura, Ikuro

    It is well known that temporal lobe in MR brain image is in use for estimating the grade of Alzheimer-type dementia. It is difficult to use only region of temporal lobe for estimating the grade of Alzheimer-type dementia. From the standpoint for supporting the medical specialists, this paper proposes a data processing approach on the automatic extraction of the intracranial region from the MR brain image. The method is able to eliminate the cranium region with the laplacian histogram method and the brainstem with the feature points which are related to the observations given by a medical specialist. In order to examine the usefulness of the proposed approach, the percentage of the temporal lobe in the intracranial region was calculated. As a result, the percentage of temporal lobe in the intracranial region on the process of the grade was in agreement with the visual sense standards of temporal lobe atrophy given by the medical specialist. It became clear that intracranial region extracted by the proposed method was good for estimating the grade of Alzheimer-type dementia.

  17. Multi-modality safety assessment of blood-brain barrier opening using focused ultrasound and definity microbubbles: a short-term study.

    Science.gov (United States)

    Baseri, Babak; Choi, James J; Tung, Yao-Sheng; Konofagou, Elisa E

    2010-09-01

    As a potentially viable method of brain drug delivery, the safety profile of blood-brain barrier (BBB) opening using focused ultrasound (FUS) and ultrasound contrast agents (UCA) needs to be established. In this study, we provide a short-term (30-min or 5-h survival) histological assessment of murine brains undergoing FUS-induced BBB opening. Forty-nine mice were intravenously injected with Definity microbubbles (0.05 microL/kg) and sonicated under the following parameters: frequency of 1.525 MHz, pulse length of 20 ms, pulse repetition frequency of 10 Hz, peak rarefactional acoustic pressures of 0.15-0.98 MPa and two 30-s sonication intervals with an intermittent 30-s delay. The BBB opening threshold was found to be 0.15-0.3 MPa based on fluorescence and magnetic resonance imaging of systemically injected tracers. Analysis of three histological measures in hematoxylin and eosin-stained sections revealed the safest acoustic pressure to be within the range of 0.3-0.46 MPa in all examined time periods post sonication. Across different pressure amplitudes, only the samples 30 min post opening showed significant difference (p < 0.05) in the average number of distinct damaged sites, microvacuolated sites, dark neurons and sites with extravasated erythrocytes. Enhanced fluorescence around severed microvessels was also noted and found to be associated with the largest tissue effects, whereas mildly diffuse BBB opening with uniform fluorescence in the parenchyma was associated with no or mild tissue injury. Region-specific areas of the sonicated brain (thalamus, hippocampal fissure, dentate gyrus and CA3 area of hippocampus) exhibited variation in fluorescence intensity based on the position, orientation and size of affected vessels. The results of this short-term histological analysis demonstrated the feasibility of a safe FUS-UCA-induced BBB opening under a specific set of sonication parameters and provided new insights on the mechanism of BBB opening.

  18. Regional magnetic resonance spectroscopy of the brain in autistic individuals

    Energy Technology Data Exchange (ETDEWEB)

    Hisaoka, S.; Harada, M.; Nishitani, H. [Dept. of Radiology, School of Medicine, University of Tokushima (Japan); Mori, K. [Dept. of Paediatrics, School of Medicine, University of Tokushima (Japan)

    2001-06-01

    We studied the variations in the concentration of metabolites with brain region and age in autistic individuals and normal controls using multiple analysis of covariance. We examined 55 autistic individuals (2-21 years old, 47 male and eight female) and 51 normal children (3 months-15 years old, 26 boys and 25 girls). Single volumes of interest were placed in the frontal, parietal and temporal region on both sides, the brain stem and cingulate gyrus. The concentration of each metabolite was quantified by the water reference method. The concentration of N-acetylaspartate in the temporal regions (Brodmann's areas 41 and 42) in the autistic individuals were significantly lower than those in the controls (P < 0.05), but concentrations in other regions were not significantly different between the autistic individuals and controls. This suggests low density or dysfunction of neurones in Brodmann's areas 41 and 42 in autistic individual, which might be related to the disturbances of the sensory speech centre (Wernicke's area) in autism. (orig.)

  19. Anxiety type modulates immediate versus delayed engagement of attention-related brain regions.

    Science.gov (United States)

    Spielberg, Jeffrey M; De Leon, Angeline A; Bredemeier, Keith; Heller, Wendy; Engels, Anna S; Warren, Stacie L; Crocker, Laura D; Sutton, Bradley P; Miller, Gregory A

    2013-09-01

    Background Habituation of the fear response, critical for the treatment of anxiety, is inconsistently observed during exposure to threatening stimuli. One potential explanation for this inconsistency is differential attentional engagement with negatively valenced stimuli as a function of anxiety type. Methods The present study tested this hypothesis by examining patterns of neural habituation associated with anxious arousal, characterized by panic symptoms and immediate engagement with negatively valenced stimuli, versus anxious apprehension, characterized by engagement in worry to distract from negatively valenced stimuli. Results As predicted, the two anxiety types evidenced distinct patterns of attentional engagement. Anxious arousal was associated with immediate activation in attention-related brain regions that habituated over time, whereas anxious apprehension was associated with delayed activation in attention-related brain regions that occurred only after habituation in a worry-related brain region. Conclusions Results further elucidate mechanisms involved in attention to negatively valenced stimuli and indicate that anxiety is a heterogeneous construct with regard to attention to such stimuli.

  20. Molecular and Functional Properties of Regional Astrocytes in the Adult Brain.

    Science.gov (United States)

    Morel, Lydie; Chiang, Ming Sum R; Higashimori, Haruki; Shoneye, Temitope; Iyer, Lakshmanan K; Yelick, Julia; Tai, Albert; Yang, Yongjie

    2017-09-06

    The molecular signature and functional properties of astroglial subtypes in the adult CNS remain largely undefined. By using translational ribosome affinity purification followed by RNA-Seq, we profiled astroglial ribosome-associated (presumably translating) mRNAs in major cortical and subcortical brain regions (cortex, hippocampus, caudate-putamen, nucleus accumbens, thalamus, and hypothalamus) of BAC aldh1l1 -translational ribosome affinity purification (TRAP) mice (both sexes). We found that the expression of astroglial translating mRNAs closely follows the dorsoventral axis, especially from cortex/hippocampus to thalamus/hypothalamus posteriorly. This region-specific expression pattern of genes, such as synaptogenic modulator sparc and transcriptional factors ( emx2 , lhx2 , and hopx ), was validated by qRT-PCR and immunostaining in brain sections. Interestingly, cortical or subcortical astrocytes selectively promote neurite growth and synaptic activity of neurons only from the same region in mismatched cocultures, exhibiting region-matched astrocyte to neuron communication. Overall, these results generated new molecular signature of astrocyte types in the adult CNS, providing insights into their origin and functional diversity. SIGNIFICANCE STATEMENT We investigated the in vivo molecular and functional heterogeneity of astrocytes inter-regionally from adult brain. Our results showed that the expression pattern of ribosome-associated mRNA profiles in astrocytes closely follows the dorsoventral axis, especially posteriorly from cortex/hippocampus to thalamus/hypothalamus. In line with this, our functional results further demonstrated region-selective roles of cortical and subcortical astrocytes in regulating cortical or subcortical neuronal synaptogenesis and maturation. These in vivo studies provide a previously uncharacterized and important molecular atlas for exploring region-specific astroglial functions. Copyright © 2017 the authors 0270-6474/17/378706-12$15.00/0.

  1. A tensor-based morphometry analysis of regional differences in brain volume in relation to prenatal alcohol exposure.

    Science.gov (United States)

    Meintjes, E M; Narr, K L; van der Kouwe, A J W; Molteno, C D; Pirnia, T; Gutman, B; Woods, R P; Thompson, P M; Jacobson, J L; Jacobson, S W

    2014-01-01

    Reductions in brain volumes represent a neurobiological signature of fetal alcohol spectrum disorders (FASD). Less clear is how regional brain tissue reductions differ after normalizing for brain size differences linked with FASD and whether these profiles can predict the degree of prenatal exposure to alcohol. To examine associations of regional brain tissue excesses/deficits with degree of prenatal alcohol exposure and diagnosis with and without correction for overall brain volume, tensor-based morphometry (TBM) methods were applied to structural imaging data from a well-characterized, demographically homogeneous sample of children diagnosed with FASD (n = 39, 9.6-11.0 years) and controls (n = 16, 9.5-11.0 years). Degree of prenatal alcohol exposure was significantly associated with regionally pervasive brain tissue reductions in: (1) the thalamus, midbrain, and ventromedial frontal lobe, (2) the superior cerebellum and inferior occipital lobe, (3) the dorsolateral frontal cortex, and (4) the precuneus and superior parietal lobule. When overall brain size was factored out of the analysis on a subject-by-subject basis, no regions showed significant associations with alcohol exposure. FASD diagnosis was associated with a similar deformation pattern, but few of the regions survived FDR correction. In data-driven independent component analyses (ICA) regional brain tissue deformations successfully distinguished individuals based on extent of prenatal alcohol exposure and to a lesser degree, diagnosis. The greater sensitivity of the continuous measure of alcohol exposure compared with the categorical diagnosis across diverse brain regions underscores the dose dependence of these effects. The ICA results illustrate that profiles of brain tissue alterations may be a useful indicator of prenatal alcohol exposure when reliable historical data are not available and facial features are not apparent.

  2. A tensor-based morphometry analysis of regional differences in brain volume in relation to prenatal alcohol exposure

    Directory of Open Access Journals (Sweden)

    E.M. Meintjes

    2014-01-01

    Full Text Available Reductions in brain volumes represent a neurobiological signature of fetal alcohol spectrum disorders (FASD. Less clear is how regional brain tissue reductions differ after normalizing for brain size differences linked with FASD and whether these profiles can predict the degree of prenatal exposure to alcohol. To examine associations of regional brain tissue excesses/deficits with degree of prenatal alcohol exposure and diagnosis with and without correction for overall brain volume, tensor-based morphometry (TBM methods were applied to structural imaging data from a well-characterized, demographically homogeneous sample of children diagnosed with FASD (n = 39, 9.6–11.0 years and controls (n = 16, 9.5–11.0 years. Degree of prenatal alcohol exposure was significantly associated with regionally pervasive brain tissue reductions in: (1 the thalamus, midbrain, and ventromedial frontal lobe, (2 the superior cerebellum and inferior occipital lobe, (3 the dorsolateral frontal cortex, and (4 the precuneus and superior parietal lobule. When overall brain size was factored out of the analysis on a subject-by-subject basis, no regions showed significant associations with alcohol exposure. FASD diagnosis was associated with a similar deformation pattern, but few of the regions survived FDR correction. In data-driven independent component analyses (ICA regional brain tissue deformations successfully distinguished individuals based on extent of prenatal alcohol exposure and to a lesser degree, diagnosis. The greater sensitivity of the continuous measure of alcohol exposure compared with the categorical diagnosis across diverse brain regions underscores the dose dependence of these effects. The ICA results illustrate that profiles of brain tissue alterations may be a useful indicator of prenatal alcohol exposure when reliable historical data are not available and facial features are not apparent.

  3. Major Shifts in Glial Regional Identity Are a Transcriptional Hallmark of Human Brain Aging

    OpenAIRE

    Soreq, Lilach; Rose, Jamie; Soreq, Eyal; Hardy, John; Trabzuni, Daniah; Cookson, Mark R.; Smith, Colin; Ryten, Mina; Patani, Rickie; Ule, Jernej

    2017-01-01

    Summary Gene expression studies suggest that aging of the human brain is determined by a complex interplay of molecular events, although both its region- and cell-type-specific consequences remain poorly understood. Here, we extensively characterized aging-altered gene expression changes across ten human brain regions from 480 individuals ranging in?age from 16 to 106 years. We show that astrocyte-?and oligodendrocyte-specific genes, but not neuron-specific genes, shift their regional express...

  4. Brain regional uptake of radioactive Sc, Mn, Zn, Se, Rb and Zr tracers into normal mice during aging

    International Nuclear Information System (INIS)

    Amano, R.; Enomoto, S.

    2001-01-01

    Radioactive multitracer technique was applied to study the brain regional uptake of trace elements by the normal mice during aging. The brain regional radioactivities of 46 Sc, 54 Mn, 65 Zn, 75 Se, 83 Rb and 88 Zr were measured 48 hours after intraperitoneal injection of a solution in normal mice aged 6 to 52 weeks to evaluate the brain regional (corpus striatum, cerebellum, cerebral cortex, hippocampus, and pons and medulla) uptakes. The radioactive distributions of 46 Sc, 54 Mn and 88 Zr tracers were variable and region-specific in the brain, while those of 65 Zn, 75 Se and 83 Rb tracers were comparable among all regions of interest. The brain regional uptakes of all tracers slightly increased with age from 10 to 28 weeks, and then remained constant during aging after 28 weeks. These uptake variations may be involved in the functional degenerative process of the blood-brain barrier during aging. (author)

  5. Regional Delivery of Chimeric Antigen Receptor-Engineered T Cells Effectively Targets HER2+ Breast Cancer Metastasis to the Brain.

    Science.gov (United States)

    Priceman, Saul J; Tilakawardane, Dileshni; Jeang, Brook; Aguilar, Brenda; Murad, John P; Park, Anthony K; Chang, Wen-Chung; Ostberg, Julie R; Neman, Josh; Jandial, Rahul; Portnow, Jana; Forman, Stephen J; Brown, Christine E

    2018-01-01

    Purpose: Metastasis to the brain from breast cancer remains a significant clinical challenge, and may be targeted with CAR-based immunotherapy. CAR design optimization for solid tumors is crucial due to the absence of truly restricted antigen expression and potential safety concerns with "on-target off-tumor" activity. Here, we have optimized HER2-CAR T cells for the treatment of breast to brain metastases, and determined optimal second-generation CAR design and route of administration for xenograft mouse models of breast metastatic brain tumors, including multifocal and leptomeningeal disease. Experimental Design: HER2-CAR constructs containing either CD28 or 4-1BB intracellular costimulatory signaling domains were compared for functional activity in vitro by measuring cytokine production, T-cell proliferation, and tumor killing capacity. We also evaluated HER2-CAR T cells delivered by intravenous, local intratumoral, or regional intraventricular routes of administration using in vivo human xenograft models of breast cancer that have metastasized to the brain. Results: Here, we have shown that HER2-CARs containing the 4-1BB costimulatory domain confer improved tumor targeting with reduced T-cell exhaustion phenotype and enhanced proliferative capacity compared with HER2-CARs containing the CD28 costimulatory domain. Local intracranial delivery of HER2-CARs showed potent in vivo antitumor activity in orthotopic xenograft models. Importantly, we demonstrated robust antitumor efficacy following regional intraventricular delivery of HER2-CAR T cells for the treatment of multifocal brain metastases and leptomeningeal disease. Conclusions: Our study shows the importance of CAR design in defining an optimized CAR T cell, and highlights intraventricular delivery of HER2-CAR T cells for treating multifocal brain metastases. Clin Cancer Res; 24(1); 95-105. ©2017 AACR . ©2017 American Association for Cancer Research.

  6. Comparison of Regional Brain Perfusion Levels in Chronically Smoking and Non-Smoking Adults

    Directory of Open Access Journals (Sweden)

    Timothy C. Durazzo

    2015-07-01

    Full Text Available Chronic cigarette smoking is associated with numerous abnormalities in brain neurobiology, but few studies specifically investigated the chronic effects of smoking (compared to the acute effects of smoking, nicotine administration, or nicotine withdrawal on cerebral perfusion (i.e., blood flow. Predominately middle-aged male (47 ± 11 years of age smokers (n = 34 and non-smokers (n = 27 were compared on regional cortical perfusion measured by continuous arterial spin labeling magnetic resonance studies at 4 Tesla. Smokers showed significantly lower perfusion than non-smokers in the bilateral medial and lateral orbitofrontal cortices, bilateral inferior parietal lobules, bilateral superior temporal gyri, left posterior cingulate, right isthmus of cingulate, and right supramarginal gyrus. Greater lifetime duration of smoking (adjusted for age was related to lower perfusion in multiple brain regions. The results indicated smokers showed significant perfusion deficits in anterior cortical regions implicated in the development, progression, and maintenance of all addictive disorders. Smokers concurrently demonstrated reduced blood flow in posterior brain regions that show morphological and metabolic aberrations as well as elevated beta amyloid deposition demonstrated by those with early stage Alzheimer disease. The findings provide additional novel evidence of the adverse effects of cigarette smoking on the human brain.

  7. Brain regions for sound processing and song release in a small grasshopper.

    Science.gov (United States)

    Balvantray Bhavsar, Mit; Stumpner, Andreas; Heinrich, Ralf

    2017-05-01

    We investigated brain regions - mostly neuropils - that process auditory information relevant for the initiation of response songs of female grasshoppers Chorthippus biguttulus during bidirectional intraspecific acoustic communication. Male-female acoustic duets in the species Ch. biguttulus require the perception of sounds, their recognition as a species- and gender-specific signal and the initiation of commands that activate thoracic pattern generating circuits to drive the sound-producing stridulatory movements of the hind legs. To study sensory-to-motor processing during acoustic communication we used multielectrodes that allowed simultaneous recordings of acoustically stimulated electrical activity from several ascending auditory interneurons or local brain neurons and subsequent electrical stimulation of the recording site. Auditory activity was detected in the lateral protocerebrum (where most of the described ascending auditory interneurons terminate), in the superior medial protocerebrum and in the central complex, that has previously been implicated in the control of sound production. Neural responses to behaviorally attractive sound stimuli showed no or only poor correlation with behavioral responses. Current injections into the lateral protocerebrum, the central complex and the deuto-/tritocerebrum (close to the cerebro-cervical fascicles), but not into the superior medial protocerebrum, elicited species-typical stridulation with high success rate. Latencies and numbers of phrases produced by electrical stimulation were different between these brain regions. Our results indicate three brain regions (likely neuropils) where auditory activity can be detected with two of these regions being potentially involved in song initiation. Copyright © 2017 Elsevier Ltd. All rights reserved.

  8. Regional differences in actomyosin contraction shape the primary vesicles in the embryonic chicken brain

    International Nuclear Information System (INIS)

    Filas, Benjamen A; Oltean, Alina; Majidi, Shabnam; Bayly, Philip V; Taber, Larry A; Beebe, David C

    2012-01-01

    In the early embryo, the brain initially forms as a relatively straight, cylindrical epithelial tube composed of neural stem cells. The brain tube then divides into three primary vesicles (forebrain, midbrain, hindbrain), as well as a series of bulges (rhombomeres) in the hindbrain. The boundaries between these subdivisions have been well studied as regions of differential gene expression, but the morphogenetic mechanisms that generate these constrictions are not well understood. Here, we show that regional variations in actomyosin-based contractility play a major role in vesicle formation in the embryonic chicken brain. In particular, boundaries did not form in brains exposed to the nonmuscle myosin II inhibitor blebbistatin, whereas increasing contractile force using calyculin or ATP deepened boundaries considerably. Tissue staining showed that contraction likely occurs at the inner part of the wall, as F-actin and phosphorylated myosin are concentrated at the apical side. However, relatively little actin and myosin was found in rhombomere boundaries. To determine the specific physical mechanisms that drive vesicle formation, we developed a finite-element model for the brain tube. Regional apical contraction was simulated in the model, with contractile anisotropy and strength estimated from contractile protein distributions and measurements of cell shapes. The model shows that a combination of circumferential contraction in the boundary regions and relatively isotropic contraction between boundaries can generate realistic morphologies for the primary vesicles. In contrast, rhombomere formation likely involves longitudinal contraction between boundaries. Further simulations suggest that these different mechanisms are dictated by regional differences in initial morphology and the need to withstand cerebrospinal fluid pressure. This study provides a new understanding of early brain morphogenesis. (paper)

  9. Brain region distribution and patterns of bioaccumulative perfluoroalkyl carboxylates and sulfonates in east greenland polar bears (Ursus maritimus).

    Science.gov (United States)

    Greaves, Alana K; Letcher, Robert J; Sonne, Christian; Dietz, Rune

    2013-03-01

    The present study investigated the comparative accumulation of perfluoroalkyl acids (PFAAs) in eight brain regions of polar bears (Ursus maritimus, n = 19) collected in 2006 from Scoresby Sound, East Greenland. The PFAAs studied were perfluoroalkyl carboxylates (PFCAs, C(6) -C(15) chain lengths) and sulfonates (C(4) , C(6) , C(8) , and C(10) chain lengths) as well as selected precursors including perfluorooctane sulfonamide. On a wet-weight basis, blood-brain barrier transport of PFAAs occurred for all brain regions, although inner regions of the brain closer to incoming blood flow (pons/medulla, thalamus, and hypothalamus) contained consistently higher PFAA concentrations compared to outer brain regions (cerebellum, striatum, and frontal, occipital, and temporal cortices). For pons/medulla, thalamus, and hypothalamus, the most concentrated PFAAs were perfluorooctane sulfonate (PFOS), ranging from 47 to 58 ng/g wet weight, and perfluorotridecanoic acid, ranging from 43 to 49 ng/g wet weight. However, PFOS and the longer-chain PFCAs (C(10) -C(15) ) were significantly (p  0.05) different among brain regions. The burden of the sum of PFCAs, perfluoroalkyl sulfonates, and perfluorooctane sulfonamide in the brain (average mass, 392 g) was estimated to be 46 µg. The present study demonstrates that both PFCAs and perfluoroalkyl sulfonates cross the blood-brain barrier in polar bears and that wet-weight concentrations are brain region-specific. Copyright © 2012 SETAC.

  10. Machine Learning Classification of Cirrhotic Patients with and without Minimal Hepatic Encephalopathy Based on Regional Homogeneity of Intrinsic Brain Activity.

    Science.gov (United States)

    Chen, Qiu-Feng; Chen, Hua-Jun; Liu, Jun; Sun, Tao; Shen, Qun-Tai

    2016-01-01

    Machine learning-based approaches play an important role in examining functional magnetic resonance imaging (fMRI) data in a multivariate manner and extracting features predictive of group membership. This study was performed to assess the potential for measuring brain intrinsic activity to identify minimal hepatic encephalopathy (MHE) in cirrhotic patients, using the support vector machine (SVM) method. Resting-state fMRI data were acquired in 16 cirrhotic patients with MHE and 19 cirrhotic patients without MHE. The regional homogeneity (ReHo) method was used to investigate the local synchrony of intrinsic brain activity. Psychometric Hepatic Encephalopathy Score (PHES) was used to define MHE condition. SVM-classifier was then applied using leave-one-out cross-validation, to determine the discriminative ReHo-map for MHE. The discrimination map highlights a set of regions, including the prefrontal cortex, anterior cingulate cortex, anterior insular cortex, inferior parietal lobule, precentral and postcentral gyri, superior and medial temporal cortices, and middle and inferior occipital gyri. The optimized discriminative model showed total accuracy of 82.9% and sensitivity of 81.3%. Our results suggested that a combination of the SVM approach and brain intrinsic activity measurement could be helpful for detection of MHE in cirrhotic patients.

  11. Regional brain glucose metabolism and blood flow in streptozocin-induced diabetic rats

    International Nuclear Information System (INIS)

    Jakobsen, J.; Nedergaard, M.; Aarslew-Jensen, M.; Diemer, N.H.

    1990-01-01

    Brain regional glucose metabolism and regional blood flow were measured from autoradiographs by the uptake of [ 3 H]-2-deoxy-D-glucose and [ 14 C]iodoantipyrine in streptozocin-induced diabetic (STZ-D) rats. After 2 days of diabetes, glucose metabolism in the neocortex, basal ganglia, and white matter increased by 34, 37, and 8%, respectively, whereas blood flow was unchanged. After 4 mo, glucose metabolism in the same three regions was decreased by 32, 43, and 60%. This reduction was paralleled by a statistically nonsignificant reduction in blood flow in neocortex and basal ganglia. It is suggested that the decrease of brain glucose metabolism in STZ-D reflects increased ketone body oxidation and reduction of electrochemical work

  12. Structural covariance of brain region volumes is associated with both structural connectivity and transcriptomic similarity.

    Science.gov (United States)

    Yee, Yohan; Fernandes, Darren J; French, Leon; Ellegood, Jacob; Cahill, Lindsay S; Vousden, Dulcie A; Spencer Noakes, Leigh; Scholz, Jan; van Eede, Matthijs C; Nieman, Brian J; Sled, John G; Lerch, Jason P

    2018-05-18

    An organizational pattern seen in the brain, termed structural covariance, is the statistical association of pairs of brain regions in their anatomical properties. These associations, measured across a population as covariances or correlations usually in cortical thickness or volume, are thought to reflect genetic and environmental underpinnings. Here, we examine the biological basis of structural volume covariance in the mouse brain. We first examined large scale associations between brain region volumes using an atlas-based approach that parcellated the entire mouse brain into 318 regions over which correlations in volume were assessed, for volumes obtained from 153 mouse brain images via high-resolution MRI. We then used a seed-based approach and determined, for 108 different seed regions across the brain and using mouse gene expression and connectivity data from the Allen Institute for Brain Science, the variation in structural covariance data that could be explained by distance to seed, transcriptomic similarity to seed, and connectivity to seed. We found that overall, correlations in structure volumes hierarchically clustered into distinct anatomical systems, similar to findings from other studies and similar to other types of networks in the brain, including structural connectivity and transcriptomic similarity networks. Across seeds, this structural covariance was significantly explained by distance (17% of the variation, up to a maximum of 49% for structural covariance to the visceral area of the cortex), transcriptomic similarity (13% of the variation, up to maximum of 28% for structural covariance to the primary visual area) and connectivity (15% of the variation, up to a maximum of 36% for structural covariance to the intermediate reticular nucleus in the medulla) of covarying structures. Together, distance, connectivity, and transcriptomic similarity explained 37% of structural covariance, up to a maximum of 63% for structural covariance to the

  13. Symbolic joint entropy reveals the coupling of various brain regions

    Science.gov (United States)

    Ma, Xiaofei; Huang, Xiaolin; Du, Sidan; Liu, Hongxing; Ning, Xinbao

    2018-01-01

    The convergence and divergence of oscillatory behavior of different brain regions are very important for the procedure of information processing. Measurements of coupling or correlation are very useful to study the difference of brain activities. In this study, EEG signals were collected from ten subjects under two conditions, i.e. eyes closed state and idle with eyes open. We propose a nonlinear algorithm, symbolic joint entropy, to compare the coupling strength among the frontal, temporal, parietal and occipital lobes and between two different states. Instead of decomposing the EEG into different frequency bands (theta, alpha, beta, gamma etc.), the novel algorithm is to investigate the coupling from the entire spectrum of brain wave activities above 4Hz. The coupling coefficients in two states with different time delay steps are compared and the group statistics are presented as well. We find that the coupling coefficient of eyes open state with delay consistently lower than that of eyes close state across the group except for one subject, whereas the results without delay are not consistent. The differences between two brain states with non-zero delay can reveal the intrinsic inter-region coupling better. We also use the well-known Hénon map data to validate the algorithm proposed in this paper. The result shows that the method is robust and has a great potential for other physiologic time series.

  14. Regional brain activation associated with addiction of computer games in adolescents

    Energy Technology Data Exchange (ETDEWEB)

    Yoo, Y. H.; Shin, O. J.; Ko, Y. W.; Kim, H. J.; Yun, M. J.; Lee, J. D. [College of Medicine, Yonsei Univ., Seoul (Korea, Republic of)

    2001-07-01

    Excessive computer game (CG) playing may cause not only behavioral addiction, but also potential negative effects on developing brain. It is necessary to reveal how brain is affected by excessive use of CG playing and behavioral addiction of it. By using PET, we address the issue seeking to identifying patterns of regional brain activation associated with behavioral addiction and excessive use of CG playing by adolescents. 6 normal control and 8 adolescents who were met by the criteria of behavioral addiction on the survey as addiction groups with an addiction of CG playing were participated. Initial screening survey which is the adapted version of DSM-IV for pathologic gambling was done. PET were performed twice in each participants both during resting state and after 20 min playing of CG. Psychological test including Youth Self Report (YSR), memory and attention test and vocabulary item from KWAIS were performed. Scores of the vocabulary item from KWAIS and social competence from YSR were significantly lower in the addiction group. On PET, addiction group showed higher resting metabolism on inferior frontal, premotor, prefrontal and superior temporal area. Adolescents with addiction of CG revealed different patterns of regional brain activation comparing to control groups. These suggest behavioral addiction and excessive use of CG may result in functional alteration of developing brain in adolescents.

  15. Regional brain activation associated with addiction of computer games in adolescents

    International Nuclear Information System (INIS)

    Yoo, Y. H.; Shin, O. J.; Ko, Y. W.; Kim, H. J.; Yun, M. J.; Lee, J. D.

    2001-01-01

    Excessive computer game (CG) playing may cause not only behavioral addiction, but also potential negative effects on developing brain. It is necessary to reveal how brain is affected by excessive use of CG playing and behavioral addiction of it. By using PET, we address the issue seeking to identifying patterns of regional brain activation associated with behavioral addiction and excessive use of CG playing by adolescents. 6 normal control and 8 adolescents who were met by the criteria of behavioral addiction on the survey as addiction groups with an addiction of CG playing were participated. Initial screening survey which is the adapted version of DSM-IV for pathologic gambling was done. PET were performed twice in each participants both during resting state and after 20 min playing of CG. Psychological test including Youth Self Report (YSR), memory and attention test and vocabulary item from KWAIS were performed. Scores of the vocabulary item from KWAIS and social competence from YSR were significantly lower in the addiction group. On PET, addiction group showed higher resting metabolism on inferior frontal, premotor, prefrontal and superior temporal area. Adolescents with addiction of CG revealed different patterns of regional brain activation comparing to control groups. These suggest behavioral addiction and excessive use of CG may result in functional alteration of developing brain in adolescents

  16. Random Forest Segregation of Drug Responses May define Regions of Biological Significance

    Directory of Open Access Journals (Sweden)

    Qasim eBukhari

    2016-03-01

    Full Text Available The ability to assess brain responses in unsupervised manner based on fMRI measure has remained a challenge. Here we have applied the Random Forest (RF method to detect differences in the pharmacological MRI (phMRI response in rats to treatment with an analgesic drug (buprenorphine as compared to control (saline. Three groups of animals were studied: two groups treated with different doses of the opioid buprenorphine, low (LD and high dose (HD, and one receiving saline. PhMRI responses were evaluated in 45 brain regions and RF analysis was applied to allocate rats to the individual treatment groups. RF analysis was able to identify drug effects based on differential phMRI responses in the hippocampus, amygdala, nucleus accumbens, superior colliculus and the lateral and posterior thalamus for drug vs. saline. These structures have high levels of mu opioid receptors. In addition these regions are involved in aversive signaling, which is inhibited by mu opioids. The results demonstrate that buprenorphine mediated phMRI responses comprise characteristic features that allow an unsupervised differentiation from placebo treated rats as well as the proper allocation to the respective drug dose group using the RF method, a method that has been successfully applied in clinical studies.

  17. Chronic ethanol exposure produces time- and brain region-dependent changes in gene coexpression networks.

    Directory of Open Access Journals (Sweden)

    Elizabeth A Osterndorff-Kahanek

    Full Text Available Repeated ethanol exposure and withdrawal in mice increases voluntary drinking and represents an animal model of physical dependence. We examined time- and brain region-dependent changes in gene coexpression networks in amygdala (AMY, nucleus accumbens (NAC, prefrontal cortex (PFC, and liver after four weekly cycles of chronic intermittent ethanol (CIE vapor exposure in C57BL/6J mice. Microarrays were used to compare gene expression profiles at 0-, 8-, and 120-hours following the last ethanol exposure. Each brain region exhibited a large number of differentially expressed genes (2,000-3,000 at the 0- and 8-hour time points, but fewer changes were detected at the 120-hour time point (400-600. Within each region, there was little gene overlap across time (~20%. All brain regions were significantly enriched with differentially expressed immune-related genes at the 8-hour time point. Weighted gene correlation network analysis identified modules that were highly enriched with differentially expressed genes at the 0- and 8-hour time points with virtually no enrichment at 120 hours. Modules enriched for both ethanol-responsive and cell-specific genes were identified in each brain region. These results indicate that chronic alcohol exposure causes global 'rewiring' of coexpression systems involving glial and immune signaling as well as neuronal genes.

  18. Molecular regionalization in the compact brain of the meiofaunal annelid Dinophilus gyrociliatus (Dinophilidae

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    Alexandra Kerbl

    2016-08-01

    Full Text Available Abstract Background Annelida is a morphologically diverse animal group that exhibits a remarkable variety in nervous system architecture (e.g., number and location of longitudinal cords, architecture of the brain. Despite this heterogeneity of neural arrangements, the molecular profiles related to central nervous system patterning seem to be conserved even between distantly related annelids. In particular, comparative molecular studies on brain and anterior neural region patterning genes have focused so far mainly on indirect-developing macrofaunal taxa. Therefore, analyses on microscopic, direct-developing annelids are important to attain a general picture of the evolutionary events underlying the vast diversity of annelid neuroanatomy. Results We have analyzed the expression domains of 11 evolutionarily conserved genes involved in brain and anterior neural patterning in adult females of the direct-developing meiofaunal annelid Dinophilus gyrociliatus. The small, compact brain shows expression of dimmed, foxg, goosecoid, homeobrain, nk2.1, orthodenticle, orthopedia, pax6, six3/6 and synaptotagmin-1. Although most of the studied markers localize to specific brain areas, the genes six3/6 and synaptotagmin-1 are expressed in nearly all perikarya of the brain. All genes except for goosecoid, pax6 and nk2.2 overlap in the anterior brain region, while the respective expression domains are more separated in the posterior brain. Conclusions Our findings reveal that the expression patterns of the genes foxg, orthodenticle, orthopedia and six3/6 correlate with those described in Platynereis dumerilii larvae, and homeobrain, nk2.1, orthodenticle and synaptotagmin-1 resemble the pattern of late larvae of Capitella teleta. Although data on other annelids are limited, molecular similarities between adult Dinophilus and larval Platynereis and Capitella suggest an overall conservation of molecular mechanisms patterning the anterior neural regions, independent

  19. Do spotty high intensity regions found in basal ganglia on MRI T2-weighted brain images of elderly subjects indicate gliosis? Comparison of brain MRI T2-weighted images of elderly subjects and necropsy brain

    International Nuclear Information System (INIS)

    Murai, Hiroshi; Hattori, Hideyuki; Matsumoto, Masayuki

    2001-01-01

    Spotty high intensity regions are frequently found on the MRI T2-weighted brain images (T2WI) of elderly people. High intensity regions with a diameter of 3 mm or less have been considered as expanded perivascular space with no pathological implications on radiological diagnosis. However, its morphometrical basis is not clear. We examined the character of the spotty regions using brain MRI of brain screening subjects, and studied morphometrically arteriolosclerosis and perivascular tissue damage using necropsy brains of subjects aged 65 years and over. The size, number and location of the spotty high intensity regions were examined using the brain MRI of 109 T2WI which is used for brain screening at Kanazawa Medical University Hospital. The frontal lobe, temporal lobe, parietal lobe, hippocampus, midbrain and basal ganglia were sampled from 15 subjects aged 65 years and over, and the tissue sections were processed for HE stain, Elastica van Gieson stain and immunostaining with GFAP. We took photographs of brain arterioli and surrounding parenchyma with a digital telescope camera and the degree of arterioscleosis and tissue damage were assessed by measurements with an image analyzer. Spotty high intensity regions on T2WI with a diameter of 3 mm or less were observed in 95.5% subjects aged 65 years and over. 69.4% spotty region was observed in basal ganglia. There was a significant correlation between age and size. In morphometrical examination, at the basal ganglia, the density of GFAP-positive astrocytes in the perivascular tissue had a significant positive correlation with the proportional thickness of the adventitia, which is an index of arteriosclerosis, and a significant negative correlation with the size of the perivascular space. The results suggested that the spotty regions in the brain MRI of elderly people do not represent dilatations of the perivascular space, but is mild brain damage caused by arteriosclerosis. (author)

  20. Altered Regional Brain Cortical Thickness in Pediatric Obstructive Sleep Apnea

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    Paul M. Macey

    2018-01-01

    Full Text Available RationaleObstructive sleep apnea (OSA affects 2–5% of all children and is associated with cognitive and behavioral deficits, resulting in poor school performance. These psychological deficits may arise from brain injury, as seen in preliminary findings of lower gray matter volume among pediatric OSA patients. However, the psychological deficits in OSA are closely related to functions in the cortex, and such brain areas have not been specifically assessed. The objective was to determine whether cortical thickness, a marker of possible brain injury, is altered in children with OSA.MethodsWe examined regional brain cortical thicknesses using high-resolution T1-weighted magnetic resonance images in 16 pediatric OSA patients (8 males; mean age ± SD = 8.4 ± 1.2 years; mean apnea/hypopnea index ± SD = 11 ± 6 events/h and 138 controls (8.3 ± 1.1 years; 62 male; 138 subjects from the NIH Pediatric MRI database to identify cortical thickness differences in pediatric OSA subjects.ResultsCortical thinning occurred in multiple regions including the superior frontal, ventral medial prefrontal, and superior parietal cortices. The left side showed greater thinning in the superior frontal cortex. Cortical thickening was observed in bilateral precentral gyrus, mid-to-posterior insular cortices, and left central gyrus, as well as right anterior insula cortex.ConclusionChanges in cortical thickness are present in children with OSA and likely indicate disruption to neural developmental processes, including maturational patterns of cortical volume increases and synaptic pruning. Regions with thicker cortices may reflect inflammation or astrocyte activation. Both the thinning and thickening associated with OSA in children may contribute to the cognitive and behavioral dysfunction frequently found in the condition.

  1. Role of Prion Replication in the Strain-dependent Brain Regional Distribution of Prions.

    Science.gov (United States)

    Hu, Ping Ping; Morales, Rodrigo; Duran-Aniotz, Claudia; Moreno-Gonzalez, Ines; Khan, Uffaf; Soto, Claudio

    2016-06-10

    One intriguing feature of prion diseases is their strain variation. Prion strains are differentiated by the clinical consequences they generate in the host, their biochemical properties, and their potential to infect other animal species. The selective targeting of these agents to specific brain structures have been extensively used to characterize prion strains. However, the molecular basis dictating strain-specific neurotropism are still elusive. In this study, isolated brain structures from animals infected with four hamster prion strains (HY, DY, 139H, and SSLOW) were analyzed for their content of protease-resistant PrP(Sc) Our data show that these strains have different profiles of PrP deposition along the brain. These patterns of accumulation, which were independent of regional PrP(C) production, were not reproduced by in vitro replication when different brain regions were used as substrate for the misfolding-amplification reaction. On the contrary, our results show that in vitro replication efficiency depended exclusively on the amount of PrP(C) present in each part of the brain. Our results suggest that the variable regional distribution of PrP(Sc) in distinct strains is not determined by differences on prion formation, but on other factors or cellular pathways. Our findings may contribute to understand the molecular mechanisms of prion pathogenesis and strain diversity. © 2016 by The American Society for Biochemistry and Molecular Biology, Inc.

  2. BRAIN NETWORKS. Correlated gene expression supports synchronous activity in brain networks.

    Science.gov (United States)

    Richiardi, Jonas; Altmann, Andre; Milazzo, Anna-Clare; Chang, Catie; Chakravarty, M Mallar; Banaschewski, Tobias; Barker, Gareth J; Bokde, Arun L W; Bromberg, Uli; Büchel, Christian; Conrod, Patricia; Fauth-Bühler, Mira; Flor, Herta; Frouin, Vincent; Gallinat, Jürgen; Garavan, Hugh; Gowland, Penny; Heinz, Andreas; Lemaître, Hervé; Mann, Karl F; Martinot, Jean-Luc; Nees, Frauke; Paus, Tomáš; Pausova, Zdenka; Rietschel, Marcella; Robbins, Trevor W; Smolka, Michael N; Spanagel, Rainer; Ströhle, Andreas; Schumann, Gunter; Hawrylycz, Mike; Poline, Jean-Baptiste; Greicius, Michael D

    2015-06-12

    During rest, brain activity is synchronized between different regions widely distributed throughout the brain, forming functional networks. However, the molecular mechanisms supporting functional connectivity remain undefined. We show that functional brain networks defined with resting-state functional magnetic resonance imaging can be recapitulated by using measures of correlated gene expression in a post mortem brain tissue data set. The set of 136 genes we identify is significantly enriched for ion channels. Polymorphisms in this set of genes significantly affect resting-state functional connectivity in a large sample of healthy adolescents. Expression levels of these genes are also significantly associated with axonal connectivity in the mouse. The results provide convergent, multimodal evidence that resting-state functional networks correlate with the orchestrated activity of dozens of genes linked to ion channel activity and synaptic function. Copyright © 2015, American Association for the Advancement of Science.

  3. Atlas based brain volumetry: How to distinguish regional volume changes due to biological or physiological effects from inherent noise of the methodology.

    Science.gov (United States)

    Opfer, Roland; Suppa, Per; Kepp, Timo; Spies, Lothar; Schippling, Sven; Huppertz, Hans-Jürgen

    2016-05-01

    Fully-automated regional brain volumetry based on structural magnetic resonance imaging (MRI) plays an important role in quantitative neuroimaging. In clinical trials as well as in clinical routine multiple MRIs of individual patients at different time points need to be assessed longitudinally. Measures of inter- and intrascanner variability are crucial to understand the intrinsic variability of the method and to distinguish volume changes due to biological or physiological effects from inherent noise of the methodology. To measure regional brain volumes an atlas based volumetry (ABV) approach was deployed using a highly elastic registration framework and an anatomical atlas in a well-defined template space. We assessed inter- and intrascanner variability of the method in 51 cognitively normal subjects and 27 Alzheimer dementia (AD) patients from the Alzheimer's Disease Neuroimaging Initiative by studying volumetric results of repeated scans for 17 compartments and brain regions. Median percentage volume differences of scan-rescans from the same scanner ranged from 0.24% (whole brain parenchyma in healthy subjects) to 1.73% (occipital lobe white matter in AD), with generally higher differences in AD patients as compared to normal subjects (e.g., 1.01% vs. 0.78% for the hippocampus). Minimum percentage volume differences detectable with an error probability of 5% were in the one-digit percentage range for almost all structures investigated, with most of them being below 5%. Intrascanner variability was independent of magnetic field strength. The median interscanner variability was up to ten times higher than the intrascanner variability. Copyright © 2016 Elsevier Inc. All rights reserved.

  4. Comparison of regional gene expression differences in the brains of the domestic dog and human

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    Kennerly Erin

    2004-11-01

    Full Text Available Abstract Comparison of the expression profiles of 2,721 genes in the cerebellum, cortex and pituitary gland of three American Staffordshire terriers, one beagle and one fox hound revealed regional expression differences in the brain but failed to reveal marked differences among breeds, or even individual dogs. Approximately 85 per cent (42 of 49 orthologue comparisons of the regional differences in the dog are similar to those that differentiate the analogous human brain regions. A smaller percentage of human differences were replicated in the dog, particularly in the cortex, which may generally be evolving more rapidly than other brain regions in mammals. This study lays the foundation for detailed analysis of the population structure of transcriptional variation as it relates to cognitive and neurological phenotypes in the domestic dog.

  5. Functional integration changes in regional brain glucose metabolism from childhood to adulthood.

    Science.gov (United States)

    Trotta, Nicola; Archambaud, Frédérique; Goldman, Serge; Baete, Kristof; Van Laere, Koen; Wens, Vincent; Van Bogaert, Patrick; Chiron, Catherine; De Tiège, Xavier

    2016-08-01

    The aim of this study was to investigate the age-related changes in resting-state neurometabolic connectivity from childhood to adulthood (6-50 years old). Fifty-four healthy adult subjects and twenty-three pseudo-healthy children underwent [(18) F]-fluorodeoxyglucose positron emission tomography at rest. Using statistical parametric mapping (SPM8), age and age squared were first used as covariate of interest to identify linear and non-linear age effects on the regional distribution of glucose metabolism throughout the brain. Then, by selecting voxels of interest (VOI) within the regions showing significant age-related metabolic changes, a psychophysiological interaction (PPI) analysis was used to search for age-induced changes in the contribution of VOIs to the metabolic activity in other brain areas. Significant linear or non-linear age-related changes in regional glucose metabolism were found in prefrontal cortices (DMPFC/ACC), cerebellar lobules, and thalamo-hippocampal areas bilaterally. Decreases were found in the contribution of thalamic, hippocampal, and cerebellar regions to DMPFC/ACC metabolic activity as well as in the contribution of hippocampi to preSMA and right IFG metabolic activities. Increases were found in the contribution of the right hippocampus to insular cortex and of the cerebellar lobule IX to superior parietal cortex metabolic activities. This study evidences significant linear or non-linear age-related changes in regional glucose metabolism of mesial prefrontal, thalamic, mesiotemporal, and cerebellar areas, associated with significant modifications in neurometabolic connectivity involving fronto-thalamic, fronto-hippocampal, and fronto-cerebellar networks. These changes in functional brain integration likely represent a metabolic correlate of age-dependent effects on sensory, motor, and high-level cognitive functional networks. Hum Brain Mapp 37:3017-3030, 2016. © 2016 Wiley Periodicals, Inc. © 2016 Wiley Periodicals, Inc.

  6. Individual differences in personality traits reflect structural variance in specific brain regions.

    Science.gov (United States)

    Gardini, Simona; Cloninger, C Robert; Venneri, Annalena

    2009-06-30

    Personality dimensions such as novelty seeking (NS), harm avoidance (HA), reward dependence (RD) and persistence (PER) are said to be heritable, stable across time and dependent on genetic and neurobiological factors. Recently a better understanding of the relationship between personality traits and brain structures/systems has become possible due to advances in neuroimaging techniques. This Magnetic Resonance Imaging (MRI) study investigated if individual differences in these personality traits reflected structural variance in specific brain regions. A large sample of eighty five young adult participants completed the Three-dimensional Personality Questionnaire (TPQ) and had their brain imaged with MRI. A voxel-based correlation analysis was carried out between individuals' personality trait scores and grey matter volume values extracted from 3D brain scans. NS correlated positively with grey matter volume in frontal and posterior cingulate regions. HA showed a negative correlation with grey matter volume in orbito-frontal, occipital and parietal structures. RD was negatively correlated with grey matter volume in the caudate nucleus and in the rectal frontal gyrus. PER showed a positive correlation with grey matter volume in the precuneus, paracentral lobule and parahippocampal gyrus. These results indicate that individual differences in the main personality dimensions of NS, HA, RD and PER, may reflect structural variance in specific brain areas.

  7. Circuit-wide Transcriptional Profiling Reveals Brain Region-Specific Gene Networks Regulating Depression Susceptibility.

    Science.gov (United States)

    Bagot, Rosemary C; Cates, Hannah M; Purushothaman, Immanuel; Lorsch, Zachary S; Walker, Deena M; Wang, Junshi; Huang, Xiaojie; Schlüter, Oliver M; Maze, Ian; Peña, Catherine J; Heller, Elizabeth A; Issler, Orna; Wang, Minghui; Song, Won-Min; Stein, Jason L; Liu, Xiaochuan; Doyle, Marie A; Scobie, Kimberly N; Sun, Hao Sheng; Neve, Rachael L; Geschwind, Daniel; Dong, Yan; Shen, Li; Zhang, Bin; Nestler, Eric J

    2016-06-01

    Depression is a complex, heterogeneous disorder and a leading contributor to the global burden of disease. Most previous research has focused on individual brain regions and genes contributing to depression. However, emerging evidence in humans and animal models suggests that dysregulated circuit function and gene expression across multiple brain regions drive depressive phenotypes. Here, we performed RNA sequencing on four brain regions from control animals and those susceptible or resilient to chronic social defeat stress at multiple time points. We employed an integrative network biology approach to identify transcriptional networks and key driver genes that regulate susceptibility to depressive-like symptoms. Further, we validated in vivo several key drivers and their associated transcriptional networks that regulate depression susceptibility and confirmed their functional significance at the levels of gene transcription, synaptic regulation, and behavior. Our study reveals novel transcriptional networks that control stress susceptibility and offers fundamentally new leads for antidepressant drug discovery. Copyright © 2016 Elsevier Inc. All rights reserved.

  8. Brain region-specific expression of MeCP2 isoforms correlates with DNA methylation within Mecp2 regulatory elements.

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    Carl O Olson

    Full Text Available MeCP2 is a critical epigenetic regulator in brain and its abnormal expression or compromised function leads to a spectrum of neurological disorders including Rett Syndrome and autism. Altered expression of the two MeCP2 isoforms, MeCP2E1 and MeCP2E2 has been implicated in neurological complications. However, expression, regulation and functions of the two isoforms are largely uncharacterized. Previously, we showed the role of MeCP2E1 in neuronal maturation and reported MeCP2E1 as the major protein isoform in the adult mouse brain, embryonic neurons and astrocytes. Recently, we showed that DNA methylation at the regulatory elements (REs within the Mecp2 promoter and intron 1 impact the expression of Mecp2 isoforms in differentiating neural stem cells. This current study is aimed for a comparative analysis of temporal, regional and cell type-specific expression of MeCP2 isoforms in the developing and adult mouse brain. MeCP2E2 displayed a later expression onset than MeCP2E1 during mouse brain development. In the adult female and male brain hippocampus, both MeCP2 isoforms were detected in neurons, astrocytes and oligodendrocytes. Furthermore, MeCP2E1 expression was relatively uniform in different brain regions (olfactory bulb, striatum, cortex, hippocampus, thalamus, brainstem and cerebellum, whereas MeCP2E2 showed differential enrichment in these brain regions. Both MeCP2 isoforms showed relatively similar distribution in these brain regions, except for cerebellum. Lastly, a preferential correlation was observed between DNA methylation at specific CpG dinucleotides within the REs and Mecp2 isoform-specific expression in these brain regions. Taken together, we show that MeCP2 isoforms display differential expression patterns during brain development and in adult mouse brain regions. DNA methylation patterns at the Mecp2 REs may impact this differential expression of Mecp2/MeCP2 isoforms in brain regions. Our results significantly contribute

  9. Disrupting the brain to validate hypotheses on the neurobiology of language

    Directory of Open Access Journals (Sweden)

    Liuba ePapeo

    2013-04-01

    Full Text Available Comprehension of words is an important part of the language faculty, involving the joint activity of frontal and temporo-parietal brain regions. Transcranial Magnetic Stimulation (TMS enables the controlled perturbation of brain activity, and thus offers a unique tool to test specific predictions about the causal relationship between brain regions and language understanding. This potential has been exploited to better define the role of regions that are classically accepted as part of the language-semantic network. For instance, TMS has contributed to establish the semantic relevance of the left anterior temporal lobe, or to solve the ambiguity between the semantic versus phonological function assigned to the left inferior frontal gyrus. We consider, more closely, the results from studies where the same technique, similar paradigms (lexical-semantic tasks and materials (words have been used to assess the relevance of regions outside the classically-defined language-semantic network – i.e., precentral motor regions – for the semantic analysis of words. This research shows that different aspects of the left precentral gyrus (primary motor and premotor sites are sensitive to the action-non action distinction of words’ meanings. However, the behavioral changes due to TMS over these sites are incongruent with what is expected after perturbation of a task-relevant brain region. Thus, the relationship between motor activity and language-semantic behavior remains far from clear. A better understanding of this issue could be guaranteed by investigating functional interactions between motor sites and semantically-relevant regions.

  10. Total regional and global number of synapses in the human brain neocortex

    NARCIS (Netherlands)

    Tang, Y.; Nyengaard, J.R.; Groot, D.M.G. de; Jorgen, H.; Gundersen, G.

    2001-01-01

    An estimator of the total number of synapses in neocortex of human autopsy brains based on unbiased stereological principles is described. Each randomly chosen cerebral hemisphere was stratified into the four major neocortical regions. Uniform sampling with a varying sampling fraction in each region

  11. Comparison of Navigation-Related Brain Regions in Migratory versus Non-Migratory Noctuid Moths

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    Liv de Vries

    2017-09-01

    Full Text Available Brain structure and function are tightly correlated across all animals. While these relations are ultimately manifestations of differently wired neurons, many changes in neural circuit architecture lead to larger-scale alterations visible already at the level of brain regions. Locating such differences has served as a beacon for identifying brain areas that are strongly associated with the ecological needs of a species—thus guiding the way towards more detailed investigations of how brains underlie species-specific behaviors. Particularly in relation to sensory requirements, volume-differences in neural tissue between closely related species reflect evolutionary investments that correspond to sensory abilities. Likewise, memory-demands imposed by lifestyle have revealed similar adaptations in regions associated with learning. Whether this is also the case for species that differ in their navigational strategy is currently unknown. While the brain regions associated with navigational control in insects have been identified (central complex (CX, lateral complex (LX and anterior optic tubercles (AOTU, it remains unknown in what way evolutionary investments have been made to accommodate particularly demanding navigational strategies. We have thus generated average-shape atlases of navigation-related brain regions of a migratory and a non-migratory noctuid moth and used volumetric analysis to identify differences. We further compared the results to identical data from Monarch butterflies. Whereas we found differences in the size of the nodular unit of the AOTU, the LX and the protocerebral bridge (PB between the two moths, these did not unambiguously reflect migratory behavior across all three species. We conclude that navigational strategy, at least in the case of long-distance migration in lepidopteran insects, is not easily deductible from overall neuropil anatomy. This suggests that the adaptations needed to ensure successful migratory behavior

  12. Effect of CDP-choline on the biosynthesis of phospholipids in brain regions during hypoxic treatment

    International Nuclear Information System (INIS)

    Alberghina, M.; Viola, M.; Serra, I.; Mistretta, A.; Giuffrida, A.M.

    1981-01-01

    Acute administration of CDP-choline (i.p. 100 mg/Kg b.w.), 10 min before the intraventricular injection of labeled precursors, [2-3H] glycerol and [1-14C]-palmitate, was able to correct the impairment caused by hypoxic treatment of lipid metabolism in some brain regions, ie, cerebral hemispheres, cerebellum, and brainstem. After CDP-choline treatment, an increase of the specific radioactivity of total lipids and of phospholipids was observed in mitochondria purified from the three above-mentioned brain regions of the hypoxic animals, while no effect on the other subcellular fractions was found. CDP-Choline had a stimulating effect particularly on the incorporation of both precursors into mitochondrial PC, PE, and polyglycerophosphatides isolated form the three brain regions examined. The results obtained show that the action of CDP-choline in restoring lipid metabolism was more pronounced in brain mitochondria, which, among subcellular fractions, were the most affected by the hypoxic treatment

  13. Enhanced peripheral visual processing in congenitally deaf humans is supported by multiple brain regions, including primary auditory cortex

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    Gregory D. Scott

    2014-03-01

    Full Text Available Brain reorganization associated with altered sensory experience clarifies the critical role of neuroplasticity in development. An example is enhanced peripheral visual processing associated with congenital deafness, but the neural systems supporting this have not been fully characterized. A gap in our understanding of deafness-enhanced peripheral vision is the contribution of primary auditory cortex. Previous studies of auditory cortex that use anatomical normalization across participants were limited by inter-subject variability of Heschl’s gyrus. In addition to reorganized auditory cortex (cross-modal plasticity, a second gap in our understanding is the contribution of altered modality-specific cortices (visual intramodal plasticity in this case, as well as supramodal and multisensory cortices, especially when target detection is required across contrasts. Here we address these gaps by comparing fMRI signal change for peripheral versus perifoveal visual stimulation (11-15° vs. 2°-7° in congenitally deaf and hearing participants in a blocked experimental design with two analytical approaches: a Heschl’s gyrus region of interest analysis and a whole brain analysis. Our results using individually-defined primary auditory cortex (Heschl’s gyrus indicate that fMRI signal change for more peripheral stimuli was greater than perifoveal in deaf but not in hearing participants. Whole-brain analyses revealed differences between deaf and hearing participants for peripheral versus perifoveal visual processing in extrastriate visual cortex including primary auditory cortex, MT+/V5, superior-temporal auditory and multisensory and/or supramodal regions, such as posterior parietal cortex, frontal eye fields, anterior cingulate, and supplementary eye fields. Overall, these data demonstrate the contribution of neuroplasticity in multiple systems including primary auditory cortex, supramodal and multisensory regions, to altered visual processing in

  14. Postmenopausal hormone therapy and regional brain volumes: the WHIMS-MRI Study.

    Science.gov (United States)

    Resnick, S M; Espeland, M A; Jaramillo, S A; Hirsch, C; Stefanick, M L; Murray, A M; Ockene, J; Davatzikos, C

    2009-01-13

    To determine whether menopausal hormone therapy (HT) affects regional brain volumes, including hippocampal and frontal regions. Brain MRI scans were obtained in a subset of 1,403 women aged 71-89 years who participated in the Women's Health Initiative Memory Study (WHIMS). WHIMS was an ancillary study to the Women's Health Initiative, which consisted of two randomized, placebo-controlled trials: 0.625 mg conjugated equine estrogens (CEE) with or without 2.5 mg medroxyprogesterone acetate (MPA) in one daily tablet. Scans were performed, on average, 3.0 years post-trial for the CEE + MPA trial and 1.4 years post-trial for the CEE-Alone trial; average on-trial follow-up intervals were 4.0 years for CEE + MPA and 5.6 years for CEE-Alone. Total brain, ventricular, hippocampal, and frontal lobe volumes, adjusted for age, clinic site, estimated intracranial volume, and dementia risk factors, were the main outcome variables. Compared with placebo, covariate-adjusted mean frontal lobe volume was 2.37 cm(3) lower among women assigned to HT (p = 0.004), mean hippocampal volume was slightly (0.10 cm(3)) lower (p = 0.05), and differences in total brain volume approached significance (p = 0.07). Results were similar for CEE + MPA and CEE-Alone. HT-associated reductions in hippocampal volumes were greatest in women with the lowest baseline Modified Mini-Mental State Examination scores (scores equine estrogens with or without MPA are associated with greater brain atrophy among women aged 65 years and older; however, the adverse effects are most evident in women experiencing cognitive deficits before initiating hormone therapy.

  15. Novel region of interest interrogation technique for diffusion tensor imaging analysis in the canine brain.

    Science.gov (United States)

    Li, Jonathan Y; Middleton, Dana M; Chen, Steven; White, Leonard; Ellinwood, N Matthew; Dickson, Patricia; Vite, Charles; Bradbury, Allison; Provenzale, James M

    2017-08-01

    Purpose We describe a novel technique for measuring diffusion tensor imaging metrics in the canine brain. We hypothesized that a standard method for region of interest placement could be developed that is highly reproducible, with less than 10% difference in measurements between raters. Methods Two sets of canine brains (three seven-week-old full-brains and two 17-week-old single hemispheres) were scanned ex-vivo on a 7T small-animal magnetic resonance imaging system. Strict region of interest placement criteria were developed and then used by two raters to independently measure diffusion tensor imaging metrics within four different white-matter regions within each specimen. Average values of fractional anisotropy, radial diffusivity, and the three eigenvalues (λ1, λ2, and λ3) within each region in each specimen overall and within each individual image slice were compared between raters by calculating the percentage difference between raters for each metric. Results The mean percentage difference between raters for all diffusion tensor imaging metrics when pooled by each region and specimen was 1.44% (range: 0.01-5.17%). The mean percentage difference between raters for all diffusion tensor imaging metrics when compared by individual image slice was 2.23% (range: 0.75-4.58%) per hemisphere. Conclusion Our results indicate that the technique described is highly reproducible, even when applied to canine specimens of differing age, morphology, and image resolution. We propose this technique for future studies of diffusion tensor imaging analysis in canine brains and for cross-sectional and longitudinal studies of canine brain models of human central nervous system disease.

  16. Regional brain structural abnormality in ischemic stroke patients: a voxel-based morphometry study

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    Ping Wu

    2016-01-01

    Full Text Available Our previous study used regional homogeneity analysis and found that activity in some brain areas of patients with ischemic stroke changed significantly. In the current study, we examined structural changes in these brain regions by taking structural magnetic resonance imaging scans of 11 ischemic stroke patients and 15 healthy participants, and analyzing the data using voxel-based morphometry. Compared with healthy participants, patients exhibited higher gray matter density in the left inferior occipital gyrus and right anterior white matter tract. In contrast, gray matter density in the right cerebellum, left precentral gyrus, right middle frontal gyrus, and left middle temporal gyrus was less in ischemic stroke patients. The changes of gray matter density in the middle frontal gyrus were negatively associated with the clinical rating scales of the Fugl-Meyer Motor Assessment (r = -0.609, P = 0.047 and the left middle temporal gyrus was negatively correlated with the clinical rating scales of the nervous functional deficiency scale (r = -0.737, P = 0.010. Our findings can objectively identify the functional abnormality in some brain regions of ischemic stroke patients.

  17. Combining region- and network-level brain-behavior relationships in a structural equation model.

    Science.gov (United States)

    Bolt, Taylor; Prince, Emily B; Nomi, Jason S; Messinger, Daniel; Llabre, Maria M; Uddin, Lucina Q

    2018-01-15

    Brain-behavior associations in fMRI studies are typically restricted to a single level of analysis: either a circumscribed brain region-of-interest (ROI) or a larger network of brain regions. However, this common practice may not always account for the interdependencies among ROIs of the same network or potentially unique information at the ROI-level, respectively. To account for both sources of information, we combined measurement and structural components of structural equation modeling (SEM) approaches to empirically derive networks from ROI activity, and to assess the association of both individual ROIs and their respective whole-brain activation networks with task performance using three large task-fMRI datasets and two separate brain parcellation schemes. The results for working memory and relational tasks revealed that well-known ROI-performance associations are either non-significant or reversed when accounting for the ROI's common association with its corresponding network, and that the network as a whole is instead robustly associated with task performance. The results for the arithmetic task revealed that in certain cases, an ROI can be robustly associated with task performance, even when accounting for its associated network. The SEM framework described in this study provides researchers additional flexibility in testing brain-behavior relationships, as well as a principled way to combine ROI- and network-levels of analysis. Copyright © 2017 Elsevier Inc. All rights reserved.

  18. Brain Regions Related to Impulsivity Mediate the Effects of Early Adversity on Antisocial Behavior.

    Science.gov (United States)

    Mackey, Scott; Chaarani, Bader; Kan, Kees-Jan; Spechler, Philip A; Orr, Catherine; Banaschewski, Tobias; Barker, Gareth; Bokde, Arun L W; Bromberg, Uli; Büchel, Christian; Cattrell, Anna; Conrod, Patricia J; Desrivières, Sylvane; Flor, Herta; Frouin, Vincent; Gallinat, Jürgen; Gowland, Penny; Heinz, Andreas; Ittermann, Bernd; Paillère Martinot, Marie-Laure; Artiges, Eric; Nees, Frauke; Papadopoulos-Orfanos, Dimitri; Poustka, Luise; Smolka, Michael N; Jurk, Sarah; Walter, Henrik; Whelan, Robert; Schumann, Gunter; Althoff, Robert R; Garavan, Hugh

    2017-08-15

    Individual differences in impulsivity and early adversity are known to be strong predictors of adolescent antisocial behavior. However, the neurobiological bases of impulsivity and their relation to antisocial behavior and adversity are poorly understood. Impulsivity was estimated with a temporal discounting task. Voxel-based morphometry was used to determine the brain structural correlates of temporal discounting in a large cohort (n = 1830) of 14- to 15-year-old children. Mediation analysis was then used to determine whether the volumes of brain regions associated with temporal discounting mediate the relation between adverse life events (e.g., family conflict, serious accidents) and antisocial behaviors (e.g., precocious sexual activity, bullying, illicit substance use). Greater temporal discounting (more impulsivity) was associated with 1) lower volume in frontomedial cortex and bilateral insula and 2) greater volume in a subcortical region encompassing the ventral striatum, hypothalamus and anterior thalamus. The volume ratio between these cortical and subcortical regions was found to partially mediate the relation between adverse life events and antisocial behavior. Temporal discounting is related to regions of the brain involved in reward processing and interoception. The results support a developmental imbalance model of impulsivity and are consistent with the idea that negative environmental factors can alter the developing brain in ways that promote antisocial behavior. Copyright © 2016 Society of Biological Psychiatry. Published by Elsevier Inc. All rights reserved.

  19. Are you better? A multi-centre study of patient-defined recovery from Complex Regional Pain Syndrome

    DEFF Research Database (Denmark)

    Llewellyn, A; McCabe, CS; Hibberd, Y

    2018-01-01

    Background: Complex Regional Pain Syndrome (CRPS) symptoms can significantly differ between patients, fluctuate over time, disappear or persist. This leads to problems in defining recovery and in evaluating the efficacy of therapeutic interventions. Objectives: To define recovery from the patient...

  20. Brain Regions Underlying Word Finding Difficulties in Temporal Lobe Epilepsy

    Science.gov (United States)

    Trebuchon-Da Fonseca, Agnes; Guedj, Eric; Alario, F-Xavier; Laguitton, Virginie; Mundler, Olivier; Chauvel, Patrick; Liegeois-Chauvel, Catherine

    2009-01-01

    Word finding difficulties are often reported by epileptic patients with seizures originating from the language dominant cerebral hemisphere, for example, in temporal lobe epilepsy. Evidence regarding the brain regions underlying this deficit comes from studies of peri-operative electro-cortical stimulation, as well as post-surgical performance.…

  1. Regional volumes and spatial volumetric distribution of gray matter in the gender dysphoric brain

    NARCIS (Netherlands)

    Hoekzema, E.; Schagen, S.E.E.; Kreukels, B.P.C.; Veltman, D.J.; Cohen-Kettenis, P.T.; Delemarre-van d Waal, H.A.; Bakkera, J.

    2015-01-01

    The sexual differentiation of the brain is primarily driven by gonadal hormones during fetal development. Leading theories on the etiology of gender dysphoria (GD) involve deviations herein. To examine whether there are signs of a sex-atypical brain development in GD, we quantified regional neural

  2. Regional volumes and spatial volumetric distribution of gray matter in the gender dysphoric brain

    NARCIS (Netherlands)

    Hoekzema, Elseline; Schagen, Sebastian E E; Kreukels, Baudewijntje P C; Veltman, Dick J; Cohen-Kettenis, Peggy T; Delemarre-van de Waal, Henriette; Bakker, J.

    The sexual differentiation of the brain is primarily driven by gonadal hormones during fetal development. Leading theories on the etiology of gender dysphoria (GD) involve deviations herein. To examine whether there are signs of a sex-atypical brain development in GD, we quantified regional neural

  3. Region-specific changes in presynaptic agmatine and glutamate levels in the aged rat brain.

    Science.gov (United States)

    Jing, Y; Liu, P; Leitch, B

    2016-01-15

    During the normal aging process, the brain undergoes a range of biochemical and structural alterations, which may contribute to deterioration of sensory and cognitive functions. Age-related deficits are associated with altered efficacy of synaptic neurotransmission. Emerging evidence indicates that levels of agmatine, a putative neurotransmitter in the mammalian brain, are altered in a region-specific manner during the aging process. The gross tissue content of agmatine in the prefrontal cortex (PFC) of aged rat brains is decreased whereas levels in the temporal cortex (TE) are increased. However, it is not known whether these changes in gross tissue levels are also mirrored by changes in agmatine levels at synapses and thus could potentially contribute to altered synaptic function with age. In the present study, agmatine levels in presynaptic terminals in the PFC and TE regions (300 terminals/region) of young (3month; n=3) and aged (24month; n=3) brains of male Sprague-Dawley rats were compared using quantitative post-embedding immunogold electron-microscopy. Presynaptic levels of agmatine were significantly increased in the TE region (60%; pagmatine and glutamate were co-localized in the same synaptic terminals, and quantitative analyses revealed significantly reduced glutamate levels in agmatine-immunopositive synaptic terminals in both regions in aged rats compared to young animals. This study, for the first time, demonstrates differential effects of aging on agmatine and glutamate in the presynaptic terminals of PFC and TE. Future research is required to understand the functional significance of these changes and the underlying mechanisms. Copyright © 2015 IBRO. Published by Elsevier Ltd. All rights reserved.

  4. Regional Brain Activation during Meditation Shows Time and Practice Effects: An Exploratory FMRI Study

    Directory of Open Access Journals (Sweden)

    E. Baron Short

    2010-01-01

    Full Text Available Meditation involves attentional regulation and may lead to increased activity in brain regions associated with attention such as dorsal lateral prefrontal cortex (DLPFC and anterior cingulate cortex (ACC. Using functional magnetic resonance imaging, we examined whether DLPFC and ACC were activated during meditation. Subjects who meditate were recruited and scanned on a 3.0 Tesla scanner. Subjects meditated for four sessions of 12 min and performed four sessions of a 6 min control task. Individual and group t-maps were generated of overall meditation response versus control response and late meditation response versus early meditation response for each subject and time courses were plotted. For the overall group (n = 13, and using an overall brain analysis, there were no statistically significant regional activations of interest using conservative thresholds. A region of interest analysis of the entire group time courses of DLPFC and ACC were statistically more active throughout meditation in comparison to the control task. Moreover, dividing the cohort into short (n = 8 and long-term (n = 5 practitioners (>10 years revealed that the time courses of long-term practitioners had significantly more consistent and sustained activation in the DLPFC and the ACC during meditation versus control in comparison to short-term practitioners. The regional brain activations in the more practised subjects may correlate with better sustained attention and attentional error monitoring. In summary, brain regions associated with attention vary over the time of a meditation session and may differ between long- and short-term meditation practitioners.

  5. Longitudinal Regional Brain Development and Clinical Risk Factors in Extremely Preterm Infants.

    Science.gov (United States)

    Kersbergen, Karina J; Makropoulos, Antonios; Aljabar, Paul; Groenendaal, Floris; de Vries, Linda S; Counsell, Serena J; Benders, Manon J N L

    2016-11-01

    To investigate third-trimester extrauterine brain growth and correlate this with clinical risk factors in the neonatal period, using serially acquired brain tissue volumes in a large, unselected cohort of extremely preterm born infants. Preterm infants (gestational age regions covering the entire brain. Multivariable regression analysis was used to determine the influence of clinical variables on volumes at both scans, as well as on volumetric growth. MRIs at term equivalent age were available for 210 infants and serial data were available for 131 infants. Growth over these 10 weeks was greatest for the cerebellum, with an increase of 258%. Sex, birth weight z-score, and prolonged mechanical ventilation showed global effects on brain volumes on both scans. The effect of brain injury on ventricular size was already visible at 30 weeks, whereas growth data and volumes at term-equivalent age revealed the effect of brain injury on the cerebellum. This study provides data about third-trimester extrauterine volumetric brain growth in preterm infants. Both global and local effects of several common clinical risk factors were found to influence serial volumetric measurements, highlighting the vulnerability of the human brain, especially in the presence of brain injury, during this period. Copyright © 2016 Elsevier Inc. All rights reserved.

  6. Aberrant regional brain activities in alcohol dependence: a functional magnetic resonance imaging study

    Directory of Open Access Journals (Sweden)

    Tu XZ

    2018-03-01

    Full Text Available Xianzhu Tu,1 Juanjuan Wang,2 Xuming Liu,3 Jiyong Zheng4 1Department of Psychiatry, Seventh People’s Hospital of Wenzhou City, Wenzhou, Zhejiang, People’s Republic of China; 2Department of Neurology, The Second Affiliated Hospital of Wenzhou Medical University, Wenzhou, Zhejiang, People’s Republic of China; 3Department of Radiology, The Third Clinical Institute Affiliated to Wenzhou Medical University, Wenzhou, Zhejiang, People’s Republic of China; 4Department of Medical Imaging, The Affiliated Huai’an No 1 People’s Hospital of Nanjing Medical University, Huai’an, Jiangsu, People’s Republic of China Objective: Whether moderate alcohol consumption has health benefits remains controversial, but the harmful effects of excessive alcohol consumption on behavior and brain function are well recognized. The aim of this study was to investigate alcohol-induced regional brain activities and their relationships with behavioral factors. Subjects and methods: A total of 29 alcohol-dependent subjects (9 females and 20 males and 29 status-matched healthy controls (11 females and 18 males were recruited. Severity of alcohol dependence questionnaire (SADQ and alcohol use disorders identification test (AUDIT were used to evaluate the severity of alcohol craving. Regional homogeneity (ReHo analysis was used to explore the alcohol-induced regional brain changes. Receiver operating characteristic (ROC curve was used to investigate the ability of regional brain activities to distinguish alcohol-dependent subjects from healthy controls. Pearson correlations were used to investigate the relationships between alcohol-induced ReHo differences and behavioral factors. Results: Alcohol-dependent subjects related to healthy controls showed higher ReHo areas in the right superior frontal gyrus (SFG, bilateral medial frontal gyrus (MFG, left precentral gyrus (PG, bilateral middle temporal gyrus (MTG, and right inferior temporal gyrus (ITG and lower ReHo areas in

  7. Acetamiprid Accumulates in Different Amounts in Murine Brain Regions

    Directory of Open Access Journals (Sweden)

    Hayato Terayama

    2016-09-01

    Full Text Available Neonicotinoids such as acetamiprid (ACE belong to a new and widely used single class of pesticides. Neonicotinoids mimic the chemical structure of nicotine and share agonist activity with the nicotine acetylcholine receptor (nAchR. Neonicotinoids are widely considered to be safe in humans; however, they have recently been implicated in a number of human health disorders. A wide range of musculoskeletal and neuromuscular disorders associated with high doses of neonicotinoids administered to animals have also been reported. Consequently, we used a mouse model to investigate the response of the central nervous system to ACE treatment. Our results show that exposure to ACE-containing water for three or seven days (decuple and centuple of no observable adverse effect level (NOAEL/day caused a decrease in body weight in 10-week old A/JJmsSlc (A/J mice. However, the treatments did not affect brain histology or expression of CD34. ACE concentrations were significantly higher in the midbrain of ACE-treated mice than that of the normal and vehicle groups. Expression levels of α7, α4, and β2 nAChRs were found to be low in the olfactory bulb and midbrain of normal mice. Furthermore, in the experimental group (centuple ACE-containing water for seven days, β2 nAChR expression decreased in many brain regions. Information regarding the amount of accumulated ACE and expression levels of the acetylcholine receptor in each region of the brain is important for understanding any clinical symptoms that may be associated with ACE exposure.

  8. 9 CFR 98.38 - Restrictions on the importation of swine semen from the APHIS-defined EU CSF region.

    Science.gov (United States)

    2010-01-01

    ... swine semen from the APHIS-defined EU CSF region. 98.38 Section 98.38 Animals and Animal Products ANIMAL... (INCLUDING POULTRY) AND ANIMAL PRODUCTS IMPORTATION OF CERTAIN ANIMAL EMBRYOS AND ANIMAL SEMEN Certain Animal Semen § 98.38 Restrictions on the importation of swine semen from the APHIS-defined EU CSF region. In...

  9. Relationship between regional brain glucose metabolism and temperament factor of personality

    Energy Technology Data Exchange (ETDEWEB)

    Cho, Sang Soo; Lee, Eun Ju; Yoon, Eun Jin; Kim, Yu Kyeong; Lee, Won Woo; Kim, Sang Eun [Seoul National University College of Medicine, Seoul (Korea, Republic of)

    2005-07-01

    Temperament factor of personality has been considered to have correlation with activity in a specific central monoaminergic system. In an attempt to explore neuronal substrate of biogenetic personality traits, we examined the relationship between regional brain glucose metabolism and temperament factor of personality. Twenty right-handed healthy subjects (age, 24{+-}4 yr: 10 females and 10 males) were studied with FDG PET. Their temperaments were assessed using the Temperament and Character Inventory (TCI), which consisted of four temperament factors (harm avoidance (HA), novelty seeking (NS), reward dependence (RD), persistency) and three personality factors. The relationship between regional glucose metabolism and each temperament score was tested using SPM99 (P < 0.005, uncorrected). NS score was negatively correlated with glucose metabolism in the frontal areas, insula, and superior temporal gyrus mainly in the right hemisphere. Positive correlation between NS score and glucose metabolism was observed in the left superior temporal gyrus. HA score showed negative correlation with glucose metabolism in the middle and orbitofrontal gyri as well as in the parahippocampal gyrus. RD score was positively correlated with glucose metabolism in the left middle frontal gyrus and negative correlated in the posterior cingulate gyrus and caudate nucleus. We identified the relationship between regional brain glucose metabolism and temperamental personality trait. Each temperament factor had a relation with functions of specific brain areas. These results help understand biological background of personality and specific feedback circuits associated with each temperament factor.

  10. Relationship between regional brain glucose metabolism and temperament factor of personality

    International Nuclear Information System (INIS)

    Cho, Sang Soo; Lee, Eun Ju; Yoon, Eun Jin; Kim, Yu Kyeong; Lee, Won Woo; Kim, Sang Eun

    2005-01-01

    Temperament factor of personality has been considered to have correlation with activity in a specific central monoaminergic system. In an attempt to explore neuronal substrate of biogenetic personality traits, we examined the relationship between regional brain glucose metabolism and temperament factor of personality. Twenty right-handed healthy subjects (age, 24±4 yr: 10 females and 10 males) were studied with FDG PET. Their temperaments were assessed using the Temperament and Character Inventory (TCI), which consisted of four temperament factors (harm avoidance (HA), novelty seeking (NS), reward dependence (RD), persistency) and three personality factors. The relationship between regional glucose metabolism and each temperament score was tested using SPM99 (P < 0.005, uncorrected). NS score was negatively correlated with glucose metabolism in the frontal areas, insula, and superior temporal gyrus mainly in the right hemisphere. Positive correlation between NS score and glucose metabolism was observed in the left superior temporal gyrus. HA score showed negative correlation with glucose metabolism in the middle and orbitofrontal gyri as well as in the parahippocampal gyrus. RD score was positively correlated with glucose metabolism in the left middle frontal gyrus and negative correlated in the posterior cingulate gyrus and caudate nucleus. We identified the relationship between regional brain glucose metabolism and temperamental personality trait. Each temperament factor had a relation with functions of specific brain areas. These results help understand biological background of personality and specific feedback circuits associated with each temperament factor

  11. Restraint of appetite and reduced regional brain volumes in anorexia nervosa: a voxel-based morphometric study

    Directory of Open Access Journals (Sweden)

    Brooks Samantha J

    2011-11-01

    Full Text Available Abstract Background Previous Magnetic Resonance Imaging (MRI studies of people with anorexia nervosa (AN have shown differences in brain structure. This study aimed to provide preliminary extensions of this data by examining how different levels of appetitive restraint impact on brain volume. Methods Voxel based morphometry (VBM, corrected for total intracranial volume, age, BMI, years of education in 14 women with AN (8 RAN and 6 BPAN and 21 women (HC was performed. Correlations between brain volume and dietary restraint were done using Statistical Package for the Social Sciences (SPSS. Results Increased right dorsolateral prefrontal cortex (DLPFC and reduced right anterior insular cortex, bilateral parahippocampal gyrus, left fusiform gyrus, left cerebellum and right posterior cingulate volumes in AN compared to HC. RAN compared to BPAN had reduced left orbitofrontal cortex, right anterior insular cortex, bilateral parahippocampal gyrus and left cerebellum. Age negatively correlated with right DLPFC volume in HC but not in AN; dietary restraint and BMI predicted 57% of variance in right DLPFC volume in AN. Conclusions In AN, brain volume differences were found in appetitive, somatosensory and top-down control brain regions. Differences in regional GMV may be linked to levels of appetitive restraint, but whether they are state or trait is unclear. Nevertheless, these discrete brain volume differences provide candidate brain regions for further structural and functional study in people with eating disorders.

  12. Regional brain network organization distinguishes the combined and inattentive subtypes of Attention Deficit Hyperactivity Disorder.

    Science.gov (United States)

    Saad, Jacqueline F; Griffiths, Kristi R; Kohn, Michael R; Clarke, Simon; Williams, Leanne M; Korgaonkar, Mayuresh S

    2017-01-01

    Attention Deficit Hyperactivity Disorder (ADHD) is characterized clinically by hyperactive/impulsive and/or inattentive symptoms which determine diagnostic subtypes as Predominantly Hyperactive-Impulsive (ADHD-HI), Predominantly Inattentive (ADHD-I), and Combined (ADHD-C). Neuroanatomically though we do not yet know if these clinical subtypes reflect distinct aberrations in underlying brain organization. We imaged 34 ADHD participants defined using DSM-IV criteria as ADHD-I ( n  = 16) or as ADHD-C ( n  = 18) and 28 matched typically developing controls, aged 8-17 years, using high-resolution T1 MRI. To quantify neuroanatomical organization we used graph theoretical analysis to assess properties of structural covariance between ADHD subtypes and controls (global network measures: path length, clustering coefficient, and regional network measures: nodal degree). As a context for interpreting network organization differences, we also quantified gray matter volume using voxel-based morphometry. Each ADHD subtype was distinguished by a different organizational profile of the degree to which specific regions were anatomically connected with other regions (i.e., in "nodal degree"). For ADHD-I (compared to both ADHD-C and controls) the nodal degree was higher in the hippocampus. ADHD-I also had a higher nodal degree in the supramarginal gyrus, calcarine sulcus, and superior occipital cortex compared to ADHD-C and in the amygdala compared to controls. By contrast, the nodal degree was higher in the cerebellum for ADHD-C compared to ADHD-I and in the anterior cingulate, middle frontal gyrus and putamen compared to controls. ADHD-C also had reduced nodal degree in the rolandic operculum and middle temporal pole compared to controls. These regional profiles were observed in the context of no differences in gray matter volume or global network organization. Our results suggest that the clinical distinction between the Inattentive and Combined subtypes of ADHD may also be

  13. Identification of Differentially Expressed Genes through Integrated Study of Alzheimer's Disease Affected Brain Regions.

    Directory of Open Access Journals (Sweden)

    Nisha Puthiyedth

    Full Text Available Alzheimer's disease (AD is the most common form of dementia in older adults that damages the brain and results in impaired memory, thinking and behaviour. The identification of differentially expressed genes and related pathways among affected brain regions can provide more information on the mechanisms of AD. In the past decade, several studies have reported many genes that are associated with AD. This wealth of information has become difficult to follow and interpret as most of the results are conflicting. In that case, it is worth doing an integrated study of multiple datasets that helps to increase the total number of samples and the statistical power in detecting biomarkers. In this study, we present an integrated analysis of five different brain region datasets and introduce new genes that warrant further investigation.The aim of our study is to apply a novel combinatorial optimisation based meta-analysis approach to identify differentially expressed genes that are associated to AD across brain regions. In this study, microarray gene expression data from 161 samples (74 non-demented controls, 87 AD from the Entorhinal Cortex (EC, Hippocampus (HIP, Middle temporal gyrus (MTG, Posterior cingulate cortex (PC, Superior frontal gyrus (SFG and visual cortex (VCX brain regions were integrated and analysed using our method. The results are then compared to two popular meta-analysis methods, RankProd and GeneMeta, and to what can be obtained by analysing the individual datasets.We find genes related with AD that are consistent with existing studies, and new candidate genes not previously related with AD. Our study confirms the up-regualtion of INFAR2 and PTMA along with the down regulation of GPHN, RAB2A, PSMD14 and FGF. Novel genes PSMB2, WNK1, RPL15, SEMA4C, RWDD2A and LARGE are found to be differentially expressed across all brain regions. Further investigation on these genes may provide new insights into the development of AD. In addition, we

  14. Combined glutamate and glutamine levels in pain-processing brain regions are associated with individual pain sensitivity.

    Science.gov (United States)

    Zunhammer, Matthias; Schweizer, Lauren M; Witte, Vanessa; Harris, Richard E; Bingel, Ulrike; Schmidt-Wilcke, Tobias

    2016-10-01

    The relationship between glutamate and γ-aminobutyric acid (GABA) levels in the living human brain and pain sensitivity is unknown. Combined glutamine/glutamate (Glx), as well as GABA levels can be measured in vivo with single-voxel proton magnetic resonance spectroscopy. In this cross-sectional study, we aimed at determining whether Glx and/or GABA levels in pain-related brain regions are associated with individual differences in pain sensitivity. Experimental heat, cold, and mechanical pain thresholds were obtained from 39 healthy, drug-free individuals (25 men) according to the quantitative sensory testing protocol and summarized into 1 composite measure of pain sensitivity. The Glx levels were measured using point-resolved spectroscopy at 3 T, within a network of pain-associated brain regions comprising the insula, the anterior cingulate cortex, the mid-cingulate cortex, the dorsolateral prefrontal cortex, and the thalamus. GABA levels were measured using GABA-edited spectroscopy (Mescher-Garwood point-resolved spectroscopy) within the insula, the anterior cingulate cortex, and the mid-cingulate cortex. Glx and/or GABA levels correlated positively across all brain regions. Gender, weekly alcohol consumption, and depressive symptoms were significantly associated with Glx and/or GABA levels. A linear regression analysis including all these factors indicated that Glx levels pooled across pain-related brain regions were positively associated with pain sensitivity, whereas no appreciable relationship with GABA was found. In sum, we show that the levels of the excitatory neurotransmitter glutamate and its precursor glutamine across pain-related brain regions are positively correlated with individual pain sensitivity. Future studies will have to determine whether our findings also apply to clinical populations.

  15. Regional differences in gene expression and promoter usage in aged human brains

    KAUST Repository

    Pardo, Luba M.

    2013-02-19

    To characterize the promoterome of caudate and putamen regions (striatum), frontal and temporal cortices, and hippocampi from aged human brains, we used high-throughput cap analysis of gene expression to profile the transcription start sites and to quantify the differences in gene expression across the 5 brain regions. We also analyzed the extent to which methylation influenced the observed expression profiles. We sequenced more than 71 million cap analysis of gene expression tags corresponding to 70,202 promoter regions and 16,888 genes. More than 7000 transcripts were differentially expressed, mainly because of differential alternative promoter usage. Unexpectedly, 7% of differentially expressed genes were neurodevelopmental transcription factors. Functional pathway analysis on the differentially expressed genes revealed an overrepresentation of several signaling pathways (e.g., fibroblast growth factor and wnt signaling) in hippocampus and striatum. We also found that although 73% of methylation signals mapped within genes, the influence of methylation on the expression profile was small. Our study underscores alternative promoter usage as an important mechanism for determining the regional differences in gene expression at old age.

  16. Recovery of resting brain connectivity ensuing mild traumatic brain injury

    Directory of Open Access Journals (Sweden)

    Rose Dawn Bharath

    2015-09-01

    Full Text Available Brains reveal amplified plasticity as they recover from an injury. We aimed to define time dependent plasticity changes in patients recovering from mild traumatic brain injury (mTBI. 25 subjects with mild head injury were longitudinally evaluated within 36 hours, 3 and 6 months using resting state functional connectivity (RSFC. Region of interest (ROI based connectivity differences over time within the patient group and in comparison with a healthy control group were analyzed at p<0.005. We found 33 distinct ROI pairs that revealed significant changes in their connectivity strength with time. Within three months, the majority of the ROI pairs had decreased connectivity in mTBI population, which increased and became comparable to healthy controls at 6 months. Initial imaging within 36 hours of injury revealed hyper connectivity predominantly involving the salience network and default mode network, which reduced at 3 months when lingual, inferior frontal and fronto-parietal networks revealed hyper connectivity. At six months all the evaluated networks revealed hyper connectivity and became comparable to the healthy controls. Our findings in a fairly homogenous group of patients with mTBI evaluated during the 6 month window of recovery defines time varying brain connectivity changes as the brain recovers from an injury. A majority of these changes were seen in the frontal and parietal lobes between 3-6 months after injury. Hyper connectivity of several networks supported normal recovery in the first six months and it remains to be seen in future studies whether this can predict an early and efficient recovery of brain function.

  17. Altered relationships between rCBF in different brain regions of never-treated schizophrenics

    International Nuclear Information System (INIS)

    Sabri, O.; Schreckenberger, M.; Cremerius, U.; Dickmann, C.; Schulz, G.; Zimny, M.; Buell, U.; Erkwoh, R.; Owega, A.; Sass, H.

    1997-01-01

    Aim of this study was to investigate the relations between regional cerebral blood flow (rCBF) of different brain regions in acute schizophrenia and following neuroleptic treatment. Methods: Twenty-two never-treated, acute schizophrenic patients were examined with HMPAO brain SPECT and assessed psychopathologically, and reexamined following neuroleptic treatment (over 96.8 days) and psychopathological remission. rCBF was determined by region/cerebellar count quotients obtained from 98 irregular regions of interest (ROIs), summed up to 11 ROIs on each hemisphere. In acute schizophrenics, interregional rCBF correlations of each ROI to every other ROI were compared to the interregional correlations following neuroleptic treatment and to those of controls. Results: All significant correlations of rCBF ratios of different brain regions were exclusively positive in controls and patients. In controls, all ROIs of one hemisphere except the mesial temporal ROI correlated significantly to its contralateral ROI. Each hemisphere showed significant frontal-temporal correlations, as well as cortical-subcortical and some cortico-limbic. In contrast, in acute schizophrenics nearly every ROI correlated significantly with every other ROI, without a grouping or relation of the rCBF of certain ROIs as in controls. After neuroleptic treatment and clinical improvement, this diffuse pattern of correlations remained. Conclusions: These results indicate differences in the neuronal interplay between regions in schizophrenic and healthy subjects. In nevertreated schizophrenics, diffuse interregional rCBF correlations can be seen as a sign of change and dysfunction of the systems regulating specificity and diversity of the neuronal functions. Neuroleptic therapy and psychopathologic remission showed no normalizing effect on interregional correlations. (orig.) [de

  18. Main effect and interactions of brain regions and gender in the calculation of volumetric asymmetry indices in healthy human brains: ANCOVA analyses of in vivo 3T MRI data.

    Science.gov (United States)

    Roldan-Valadez, Ernesto; Rios, Camilo; Suarez-May, Marcela A; Favila, Rafel; Aguilar-Castañeda, Erika

    2013-12-01

    Macroanatomical right-left hemispheric differences in the brain are termed asymmetries, although there is no clear information on the global influence of gender and brain-regions. The aim of this study was to evaluate the main effects and interactions of these variables on the measurement of volumetric asymmetry indices (VAIs). Forty-seven healthy young-adult volunteers (23 males, 24 females) agreed to undergo brain magnetic resonance imaging in a 3T scanner. Image post processing using voxel-based volumetry allowed the calculation of 54 VAIs from the frontal, temporal, parietal and occipital lobes, limbic system, basal ganglia, and cerebellum for each cerebral hemisphere. Multivariate ANCOVA analysis calculated the main effects and interactions on VAIs of gender and brain regions controlling the effect of age. The only significant finding was the main effect of brain regions (F (6, 9373.605) 44.369, P gender and brain regions (F (6, 50.517) .239, P = .964). Volumetric asymmetries are present across all brain regions, with larger values found in the limbic system and parietal lobe. The absence of a significant influence of gender and age in the evaluation of the numerous measurements generated by multivariate analyses in this study should not discourage researchers to report and interpret similar results, as this topic still deserves further assessment. Copyright © 2013 Wiley Periodicals, Inc.

  19. Age- and gender-related regional variations of human brain cortical thickness, complexity, and gradient in the third decade.

    Science.gov (United States)

    Creze, Maud; Versheure, Leslie; Besson, Pierre; Sauvage, Chloe; Leclerc, Xavier; Jissendi-Tchofo, Patrice

    2014-06-01

    Brain functional and cytoarchitectural maturation continue until adulthood, but little is known about the evolution of the regional pattern of cortical thickness (CT), complexity (CC), and intensity or gradient (CG) in young adults. We attempted to detect global and regional age- and gender-related variations of brain CT, CC, and CG, in 28 healthy young adults (19-33 years) using a three-dimensional T1 -weighted magnetic resonance imaging sequence and surface-based methods. Whole brain interindividual variations of CT and CG were similar to that in the literature. As a new finding, age- and gender-related variations significantly affected brain complexity (P gender), all in the right hemisphere. Regions of interest analyses showed age and gender significant interaction (P left inferior parietal. In addition, we found significant inverse correlations between CT and CC and between CT and CG over the whole brain and markedly in precentral and occipital areas. Our findings differ in details from previous reports and may correlate with late brain maturation and learning plasticity in young adults' brain in the third decade. Copyright © 2013 Wiley Periodicals, Inc.

  20. Optimizing full-brain coverage in human brain MRI through population distributions of brain size

    NARCIS (Netherlands)

    Mennes, M.; Jenkinson, M.; Valabregue, R.; Buitelaar, J.K.; Beckmann, C.F.; Smith, S.

    2014-01-01

    When defining an MRI protocol, brain researchers need to set multiple interdependent parameters that define repetition time (TR), voxel size, field-of-view (FOV), etc. Typically, researchers aim to image the full brain, making the expected FOV an important parameter to consider. Especially in 2D-EPI

  1. Specific Regional and Age-Related Small Noncoding RNA Expression Patterns Within Superior Temporal Gyrus of Typical Human Brains Are Less Distinct in Autism Brains.

    Science.gov (United States)

    Stamova, Boryana; Ander, Bradley P; Barger, Nicole; Sharp, Frank R; Schumann, Cynthia M

    2015-12-01

    Small noncoding RNAs play a critical role in regulating messenger RNA throughout brain development and when altered could have profound effects leading to disorders such as autism spectrum disorders (ASD). We assessed small noncoding RNAs, including microRNA and small nucleolar RNA, in superior temporal sulcus association cortex and primary auditory cortex in typical and ASD brains from early childhood to adulthood. Typical small noncoding RNA expression profiles were less distinct in ASD, both between regions and changes with age. Typical micro-RNA coexpression associations were absent in ASD brains. miR-132, miR-103, and miR-320 micro-RNAs were dysregulated in ASD and have previously been associated with autism spectrum disorders. These diminished region- and age-related micro-RNA expression profiles are in line with previously reported findings of attenuated messenger RNA and long noncoding RNA in ASD brain. This study demonstrates alterations in superior temporal sulcus in ASD, a region implicated in social impairment, and is the first to demonstrate molecular alterations in the primary auditory cortex. © The Author(s) 2015.

  2. Regional brain glucose use in unstressed rats after two days of starvation

    International Nuclear Information System (INIS)

    Mans, A.M.; Davis, D.W.; Hawkins, R.A.

    1987-01-01

    Regional brain glucose use was measured in conscious, unrestrained, fed rats and after 2 days of starvation, using quantitative autoradiography and [6- 14 C]glucose. Plasma glucose, lactate, and ketone body concentrations and brain glucose and lactate content were measured in separate groups of rats. Glucose concentrations were lower in starved rats in both plasma and brain; plasma ketone body concentrations were elevated. Glucose use was found to be lower throughout the brain by about 12%. While some areas seemed to be affected more than others, statistical analysis showed that none were exceptionally different. The results could not be explained by increased loss of 14 C as lactate or pyruvate during the experimental period, because the arteriovenous differences of these species were insignificant. The calculated contribution by ketone bodies to the total energy consumption was between 3 and 9% for the brain as a whole in the starved rats and could, therefore, partially account for the depression seen in glucose use. It was concluded that glucose oxidation is slightly depressed throughout the brain after 2 days of starvation

  3. Protein profiles of serum, brain regions and hypophyses of pubertal ...

    African Journals Online (AJOL)

    The effects of dietary fumonisin B1 (FB1 ), a toxin produced mainly by Fusarium verticillioides and F. proliferatum that grow on maize worldwide, on protein profiles of serum, brain regions and hypophyses were studied in 24 male Large White weanling pigs randomly divided into four groups (n = 6). In a completely ...

  4. Financial literacy is associated with medial brain region functional connectivity in old age.

    Science.gov (United States)

    Han, S Duke; Boyle, Patricia A; Yu, Lei; Fleischman, Debra A; Arfanakis, Konstantinos; Leurgans, Sue; Bennett, David A

    2014-01-01

    Financial literacy refers to the ability to access and utilize financial information in ways that promote better outcomes. In old age, financial literacy has been associated with a wide range of positive characteristics; however, the neural correlates remain unclear. Recent work has suggested greater co-activity between anterior-posterior medial brain regions is associated with better brain functioning. We hypothesized financial literacy would be associated with this pattern. We assessed whole-brain functional connectivity to a posterior cingulate cortex (PCC) seed region of interest (ROI) in 138 participants of the Rush Memory and Aging Project. Results revealed financial literacy was associated with greater functional connectivity between the PCC and three regions: the right ventromedial prefrontal cortex (vmPFC), the left postcentral gyrus, and the right precuneus. Results also revealed financial literacy was associated negatively with functional connectivity between the PCC and left caudate. Post hoc analyses showed the PCC-vmPFC relationship accounted for the most variance in a regression model adjusted for all four significant functional connectivity relationships, demographic factors, and global cognition. These findings provide information on the neural mechanisms associated with financial literacy in old age. Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.

  5. Deficits in Regional Cerebral Blood Flow on Brain SPECT Predict Treatment Resistant Depression.

    Science.gov (United States)

    Amen, Daniel G; Taylor, Derek V; Meysami, Somayeh; Raji, Cyrus A

    2018-03-22

    Depression remains an important risk factor for Alzheimer's disease, yet few neuroimaging biomarkers are available to identify treatment response in depression. To analyze and compare functional perfusion neuroimaging in persons with treatment resistant depression (TRD) compared to those experiencing full remission. A total of 951 subjects from a community psychiatry cohort were scanned with perfusion single photon emission computed tomography (SPECT) of the brain in both resting and task related settings. Of these, 78% experienced either full remission (n = 506) or partial remission (n = 237) and 11% were minimally responsive (n = 103) or non-responsive (11%. n = 106). Severity of depression symptoms were used to define these groups with changes in the Beck Depression Inventory prior to and following treatment. Voxel-based analyses of brain SPECT images from full remission compared to the worsening group was conducted with the statistical parametric mapping software, version 8 (SPM 8). Multiple comparisons were accounted for with a false discovery rate (p <  0.001). Persons with depression that worsened following treatment had reduced cerebral perfusion compared to full remission in the multiple regions including the bilateral frontal lobes, right hippocampus, left precuneus, and cerebellar vermis. Such differences were observed on both resting and concentration SPECT scans. Our findings identify imaging-based biomarkers in persons with depression related to treatment response. These findings have implications in understanding both depression to prognosis and its role as a risk factor for dementia.

  6. The overlapping community structure of structural brain network in young healthy individuals.

    Directory of Open Access Journals (Sweden)

    Kai Wu

    2011-05-01

    Full Text Available Community structure is a universal and significant feature of many complex networks in biology, society, and economics. Community structure has also been revealed in human brain structural and functional networks in previous studies. However, communities overlap and share many edges and nodes. Uncovering the overlapping community structure of complex networks remains largely unknown in human brain networks. Here, using regional gray matter volume, we investigated the structural brain network among 90 brain regions (according to a predefined anatomical atlas in 462 young, healthy individuals. Overlapped nodes between communities were defined by assuming that nodes (brain regions can belong to more than one community. We demonstrated that 90 brain regions were organized into 5 overlapping communities associated with several well-known brain systems, such as the auditory/language, visuospatial, emotion, decision-making, social, control of action, memory/learning, and visual systems. The overlapped nodes were mostly involved in an inferior-posterior pattern and were primarily related to auditory and visual perception. The overlapped nodes were mainly attributed to brain regions with higher node degrees and nodal efficiency and played a pivotal role in the flow of information through the structural brain network. Our results revealed fuzzy boundaries between communities by identifying overlapped nodes and provided new insights into the understanding of the relationship between the structure and function of the human brain. This study provides the first report of the overlapping community structure of the structural network of the human brain.

  7. Region-specific maturation of cerebral cortex in human fetal brain: diffusion tensor imaging and histology

    International Nuclear Information System (INIS)

    Trivedi, Richa; Gupta, Rakesh K.; Saksena, Sona; Husain, Nuzhat; Srivastava, Savita; Rathore, Ram K.S.; Sarma, Manoj K.; Malik, Gyanendra K.; Das, Vinita; Pradhan, Mandakini; Pandey, Chandra M.; Narayana, Ponnada A.

    2009-01-01

    In this study, diffusion tensor imaging (DTI) and glial fibrillary acidic protein (GFAP) immunohistochemical analysis in different cortical regions in fetal brains at different gestational age (GA) were performed. DTI was performed on 50 freshly aborted fetal brains with GA ranging from 12 to 42 weeks to compare age-related fractional anisotropy (FA) changes in different cerebral cortical regions that include frontal, parietal, occipital, and temporal lobes at the level of thalami. GFAP immunostaining was performed and the percentage of GFAP-positive areas was quantified. The cortical FA values in the frontal lobe peaked at around 26 weeks of GA, occipital and temporal lobes at around 20 weeks, and parietal lobe at around 23 weeks. A significant, but modest, positive correlation (r=0.31, p=0.02) was observed between cortical FA values and percentage area of GFAP expression in cortical region around the time period during which the migrational events are at its peak, i.e., GA ≤ 28 weeks for frontal cortical region and GA≤22 weeks for rest of the lobes. The DTI-derived FA quantification with its GFAP immunohistologic correlation in cortical regions of the various lobes of the cerebral hemispheres supports region-specific migrational and maturational events in human fetal brain. (orig.)

  8. Region-specific maturation of cerebral cortex in human fetal brain: diffusion tensor imaging and histology

    Energy Technology Data Exchange (ETDEWEB)

    Trivedi, Richa; Gupta, Rakesh K.; Saksena, Sona [Sanjay Gandhi Post Graduate Institute of Medical Sciences, Department of Radiodiagnosis, Lucknow, UP (India); Husain, Nuzhat; Srivastava, Savita [CSM Medical University, Department of Pathology, Lucknow (India); Rathore, Ram K.S.; Sarma, Manoj K. [Indian Institute of Technology, Department of Mathematics and Statistics, Kanpur (India); Malik, Gyanendra K. [CSM Medical University, Department of Pediatrics, Lucknow (India); Das, Vinita [CSM Medical University, Department of Obstetrics and Gynecology, Lucknow (India); Pradhan, Mandakini [Sanjay Gandhi Postgraduate Institute of Medical Sciences, Department of Medical Genetics, Lucknow (India); Pandey, Chandra M. [Sanjay Gandhi Postgraduate Institute of Medical Sciences, Department of Biostatistics, Lucknow (India); Narayana, Ponnada A. [University of Texas Medical School at Houston, Department of Diagnostic and Interventional Imaging, Houston, TX (United States)

    2009-09-15

    In this study, diffusion tensor imaging (DTI) and glial fibrillary acidic protein (GFAP) immunohistochemical analysis in different cortical regions in fetal brains at different gestational age (GA) were performed. DTI was performed on 50 freshly aborted fetal brains with GA ranging from 12 to 42 weeks to compare age-related fractional anisotropy (FA) changes in different cerebral cortical regions that include frontal, parietal, occipital, and temporal lobes at the level of thalami. GFAP immunostaining was performed and the percentage of GFAP-positive areas was quantified. The cortical FA values in the frontal lobe peaked at around 26 weeks of GA, occipital and temporal lobes at around 20 weeks, and parietal lobe at around 23 weeks. A significant, but modest, positive correlation (r=0.31, p=0.02) was observed between cortical FA values and percentage area of GFAP expression in cortical region around the time period during which the migrational events are at its peak, i.e., GA {<=} 28 weeks for frontal cortical region and GA{<=}22 weeks for rest of the lobes. The DTI-derived FA quantification with its GFAP immunohistologic correlation in cortical regions of the various lobes of the cerebral hemispheres supports region-specific migrational and maturational events in human fetal brain. (orig.)

  9. Involvement of high plasma corticosterone status and activation of brain regional serotonin metabolism in long-term erythrosine-induced rearing motor hyper activity in young adult male rats.

    Science.gov (United States)

    Dalal, Arindam; Poddar, Mrinal K

    2010-07-01

    Long-term consumption of artificial food color(s) can induce behavioral hyperactivity in human and experimental animals, but no neurobiochemical mechanism is defined. This study investigates the role of brain regional serotonin metabolism including its turnover, MAO-A activity, and plasma corticosterone status in relation to behavioral disturbances due to an artificial food color, erythrosine. Long-term (15 or 30 consecutive days) erythrosine administration with higher dosage (10 or 100 mg/kg/day, p.o.) produced optimal hyperactive state in exploratory behavior (rearing motor activity) after 2 h of last erythrosine administration, in young adult male albino rats. Erythrosine-induced stimulation in brain regional (medulla-pons, hypothalamus, hippocampus, and corpus striatum) serotonin metabolism (measuring steady state levels of 5-HT and 5-HIAA, MAO-A activity), including its turnover (pargyline-induced 5-HT accumulation and 5-HIAA declination rate), as well as plasma corticosterone were also observed depending on dosage(s) and duration(s) of erythrosine administration under similar experimental conditions. The lower dosage of erythrosine (1 mg/kg/day, p.o.) under similar conditions did not affect either of the above. These findings suggests (a) the induction as well as optimal effect of long-term erythrosine (artificial food color) on behavioral hyperactivity in parallel with increase in 5-HT level in brain regions, (b) the activation of brain regional serotonin biosynthesis in accordance with plasma corticosterone status under such behavioral hyperactivity, and (c) a possible inhibitory influence of the enhanced glucocorticoids-serotonin interaction on erythrosine-induced rearing motor hyperactivity in young adult mammals.

  10. Metabolic enhancer piracetam attenuates rotenone induced oxidative stress: a study in different rat brain regions.

    Science.gov (United States)

    Verma, Dinesh Kumar; Joshi, Neeraj; Raju, Kunumuri Sivarama; Wahajuddin, Muhammad; Singh, Rama Kant; Singh, Sarika

    2015-01-01

    Piracetam is clinically being used nootropic drug but the details of its neuroprotective mechanism are not well studied. The present study was conducted to assess the effects of piracetam on rotenone induced oxidative stress by using both ex vivo and in vivo test systems. Rats were treated with piracetam (600 mg/kg b.w. oral) for seven constitutive days prior to rotenone administration (intracerebroventricular, 12 µg) in rat brain. Rotenone induced oxidative stress was assessed after 1 h and 24 h of rotenone administration. Ex vivo estimations were performed by using two experimental designs. In one experimental design the rat brain homogenate was treated with rotenone (1 mM, 2 mM and 4 mM) and rotenone+piracetam (10 mM) for 1 h. While in second experimental design the rats were pretreated with piracetam for seven consecutive days. On eighth day the rats were sacrificed, brain homogenate was prepared and treated with rotenone (1 mM, 2 mM and 4mM) for 1h. After treatment the glutathione (GSH) and malondialdehyde (MDA) levels were estimated in brain homogenate. In vivo study showed that pretreatment of piracetam offered significant protection against rotenone induced decreased GSH and increased MDA level though the protection was region specific. But the co-treatment of piracetam with rotenone did not offer significant protection against rotenone induced oxidative stress in ex vivo study. Whereas ex vivo experiments in rat brain homogenate of piracetam pretreated rats, showed the significant protection against rotenone induced oxidative stress. Findings indicated that pretreatment of piracetam significantly attenuated the rotenone induced oxidative stress though the protection was region specific. Piracetam treatment to rats led to its absorption and accumulation in different brain regions as assessed by liquid chromatography mass spectrometry/mass spectrometry. In conclusion, study indicates the piracetam is able to enhance the antioxidant capacity in brain cells

  11. Mapping the regional influence of genetics on brain structure variability--a tensor-based morphometry study.

    Science.gov (United States)

    Brun, Caroline C; Leporé, Natasha; Pennec, Xavier; Lee, Agatha D; Barysheva, Marina; Madsen, Sarah K; Avedissian, Christina; Chou, Yi-Yu; de Zubicaray, Greig I; McMahon, Katie L; Wright, Margaret J; Toga, Arthur W; Thompson, Paul M

    2009-10-15

    Genetic and environmental factors influence brain structure and function profoundly. The search for heritable anatomical features and their influencing genes would be accelerated with detailed 3D maps showing the degree to which brain morphometry is genetically determined. As part of an MRI study that will scan 1150 twins, we applied Tensor-Based Morphometry to compute morphometric differences in 23 pairs of identical twins and 23 pairs of same-sex fraternal twins (mean age: 23.8+/-1.8 SD years). All 92 twins' 3D brain MRI scans were nonlinearly registered to a common space using a Riemannian fluid-based warping approach to compute volumetric differences across subjects. A multi-template method was used to improve volume quantification. Vector fields driving each subject's anatomy onto the common template were analyzed to create maps of local volumetric excesses and deficits relative to the standard template. Using a new structural equation modeling method, we computed the voxelwise proportion of variance in volumes attributable to additive (A) or dominant (D) genetic factors versus shared environmental (C) or unique environmental factors (E). The method was also applied to various anatomical regions of interest (ROIs). As hypothesized, the overall volumes of the brain, basal ganglia, thalamus, and each lobe were under strong genetic control; local white matter volumes were mostly controlled by common environment. After adjusting for individual differences in overall brain scale, genetic influences were still relatively high in the corpus callosum and in early-maturing brain regions such as the occipital lobes, while environmental influences were greater in frontal brain regions that have a more protracted maturational time-course.

  12. Regional cerebral blood flow and brain atrophy in senile dementia of Alzheimer type (SDAT)

    International Nuclear Information System (INIS)

    Okada, Kazunori; Kobayashi, Shoutai; Yamaguchi, Shuhei; Kitani, Mituhiro; Tsunematsu, Tokugoro

    1987-01-01

    To investigate the relationship between the reduction of cerebal blood flow and brain atrophy in SDAT, these were measured in 13 cases of senile dementia of Alzheimer type, and compared to 15 cases of multi-infarct Dementia, 39 cases of lacunar infarction without dementia (non-demented CVD group) and 69 cases of aged normal control. Brain atrophy was evaluated by two-dimensional method on CT film by digitizer and regional cerebral blood flow (rCBF) was measured by 133 Xe inhalation method. The degree of brain atrophy in SDAT was almost similar of that of MID. But it was more severe than that of non-demented group. MID showed the lowest rCBF among these groups. SDAT showed significantly lower rCBF than that of aged control, but rCBF in SDAT was equal to that of lacunar stroke without dementia. Focal reduction of cerebral blood flow in bilateral fronto-parietal and left occipital regions were observed in SDAT. Verbal intelligence score (Hasegawa's score) correlated with rCBF and brain atrophy index in MID, and a tendency of correlation between rCBF and brain atrophy in MID was also observed. However, there was no correlation among those indices in SDAT. These findings suggest that the loss of brain substance dose not correspond to the reduction of rCBF in SDAT and simultaneous measurement of rCBF and brain atrophy was useful to differ SDAT from MID. (author)

  13. Glucose metabolism in different regions of the rat brain under hypokinetic stress influence

    Science.gov (United States)

    Konitzer, K.; Voigt, S.

    1980-01-01

    Glucose metabolism in rats kept under long term hypokinetic stress was studied in 7 brain regions. Determination was made of the regional levels of glucose, lactate, glutamate, glutamine, aspartate, gamma-aminobutyrate and the incorporation of C-14 from plasma glucose into these metabolites, in glycogen and protein. From the content and activity data the regional glucose flux was approximated quantitatively. Under normal conditions the activity gradient cortex and frontal pole cerebellum, thalamus and mesencephalon, hypothalamus and pons and medulla is identical with that of the regional blood supply (measured with I131 serum albumin as the blood marker). Within the first days of immobilization a functional hypoxia occurred in all brain regions and the utilization of cycle amino acids for protein synthesis was strongly diminished. After the first week of stress the capillary volumes of all regions increased, aerobic glucose metabolism was enhanced (factors 1.3 - 2.0) and the incorporation of glucose C-14 via cycle amino acids into protein was considerably potentiated. The metabolic parameters normalized between the 7th and 11th week of stress. Blood supply and metabolic rate increased most in the hypothalamus.

  14. Repeated verum but not placebo acupuncture normalizes connectivity in brain regions dysregulated in chronic pain

    Directory of Open Access Journals (Sweden)

    Natalia Egorova

    2015-01-01

    Full Text Available Acupuncture, an ancient East Asian therapy, is aimed at rectifying the imbalance within the body caused by disease. Studies evaluating the efficacy of acupuncture with neuroimaging tend to concentrate on brain regions within the pain matrix, associated with acute pain. We, however, focused on the effect of repeated acupuncture treatment specifically on brain regions known to support functions dysregulated in chronic pain disorders. Transition to chronic pain is associated with increased attention to pain, emotional rumination, nociceptive memory and avoidance learning, resulting in brain connectivity changes, specifically affecting the periaqueductal gray (PAG, medial frontal cortex (MFC and bilateral hippocampus (Hpc. We demonstrate that the PAG–MFC and PAG–Hpc connectivity in patients with chronic pain due to knee osteoarthritis indeed correlates with clinical severity scores and further show that verum acupuncture-induced improvement in pain scores (compared to sham is related to the modulation of PAG–MFC and PAG–Hpc connectivity in the predicted direction. This study shows that repeated verum acupuncture might act by restoring the balance in the connectivity of the key pain brain regions, altering pain-related attention and memory.

  15. Regional neural tube closure defined by the Grainy head-like transcription factors.

    Science.gov (United States)

    Rifat, Yeliz; Parekh, Vishwas; Wilanowski, Tomasz; Hislop, Nikki R; Auden, Alana; Ting, Stephen B; Cunningham, John M; Jane, Stephen M

    2010-09-15

    Primary neurulation in mammals has been defined by distinct anatomical closure sites, at the hindbrain/cervical spine (closure 1), forebrain/midbrain boundary (closure 2), and rostral end of the forebrain (closure 3). Zones of neurulation have also been characterized by morphologic differences in neural fold elevation, with non-neural ectoderm-induced formation of paired dorso-lateral hinge points (DLHP) essential for neural tube closure in the cranial and lower spinal cord regions, and notochord-induced bending at the median hinge point (MHP) sufficient for closure in the upper spinal region. Here we identify a unifying molecular basis for these observations based on the function of the non-neural ectoderm-specific Grainy head-like genes in mice. Using a gene-targeting approach we show that deletion of Grhl2 results in failed closure 3, with mutants exhibiting a split-face malformation and exencephaly, associated with failure of neuro-epithelial folding at the DLHP. Loss of Grhl3 alone defines a distinct lower spinal closure defect, also with defective DLHP formation. The two genes contribute equally to closure 2, where only Grhl gene dosage is limiting. Combined deletion of Grhl2 and Grhl3 induces severe rostral and caudal neural tube defects, but DLHP-independent closure 1 proceeds normally in the upper spinal region. These findings provide a molecular basis for non-neural ectoderm mediated formation of the DLHP that is critical for complete neuraxis closure. (c) 2010 Elsevier Inc. All rights reserved.

  16. Aging-induced changes in brain regional serotonin receptor binding: Effect of Carnosine.

    Science.gov (United States)

    Banerjee, S; Poddar, M K

    2016-04-05

    Monoamine neurotransmitter, serotonin (5-HT) has its own specific receptors in both pre- and post-synapse. In the present study the role of carnosine on aging-induced changes of [(3)H]-5-HT receptor binding in different brain regions in a rat model was studied. The results showed that during aging (18 and 24 months) the [(3)H]-5-HT receptor binding was reduced in hippocampus, hypothalamus and pons-medulla with a decrease in their both Bmax and KD but in cerebral cortex the [(3)H]-5-HT binding was increased with the increase of its only Bmax. The aging-induced changes in [(3)H]-5-HT receptor binding with carnosine (2.0 μg/kg/day, intrathecally, for 21 consecutive days) attenuated in (a) 24-month-aged rats irrespective of the brain regions with the attenuation of its Bmax except hypothalamus where both Bmax and KD were significantly attenuated, (b) hippocampus and hypothalamus of 18-month-aged rats with the attenuation of its Bmax, and restored toward the [(3)H]-5-HT receptor binding that observed in 4-month-young rats. The decrease in pons-medullary [(3)H]-5-HT binding including its Bmax of 18-month-aged rats was promoted with carnosine without any significant change in its cerebral cortex. The [(3)H]-5-HT receptor binding with the same dosages of carnosine in 4-month-young rats (a) increased in the cerebral cortex and hippocampus with the increase in their only Bmax whereas (b) decreased in hypothalamus and pons-medulla with a decrease in their both Bmax and KD. These results suggest that carnosine treatment may (a) play a preventive role in aging-induced brain region-specific changes in serotonergic activity (b) not be worthy in 4-month-young rats in relation to the brain regional serotonergic activity. Copyright © 2016 IBRO. Published by Elsevier Ltd. All rights reserved.

  17. Regional amino acid transport into brain during diabetes: Effect of plasma amino acids

    International Nuclear Information System (INIS)

    Mans, A.M.; DeJoseph, M.R.; Davis, D.W.; Hawkins, R.A.

    1987-01-01

    Transport of phenylalanine and lysine into the brain was measured in 4-wk streptozotocin-diabetic rats to assess the effect on the neutral and basic amino acid transport systems at the blood-brain barrier. Amino acid concentrations in plasma and brain were also measured. Regional permeability-times-surface area (PS) products and influx were determined using a continuous infusion method and quantitative autoradiography. The PS of phenylalanine was decreased by an average of 40% throughout the entire brain. Influx was depressed by 35%. The PS of lysine was increased by an average of 44%, but the influx was decreased by 27%. Several plasma neutral amino acids (branched chain) were increased, whereas all basic amino acids were decreased. Brain tryptophan, phenylalanine, tyrosine, methionine, and lysine contents were markedly decreased. The transport changes were almost entirely accounted for by the alterations in the concentrations of the plasma amino acids that compete for the neutral and basic amino acid carriers. The reduced influx could be responsible for the low brain content of some essential amino acids, with possibly deleterious consequences for brain functions

  18. Behavioral stress alters corticolimbic microglia in a sex- and brain region-specific manner.

    Science.gov (United States)

    Bollinger, Justin L; Collins, Kaitlyn E; Patel, Rushi; Wellman, Cara L

    2017-01-01

    Women are more susceptible to numerous stress-linked psychological disorders (e.g., depression) characterized by dysfunction of corticolimbic brain regions critical for emotion regulation and cognitive function. Although sparsely investigated, a number of studies indicate sex differences in stress effects on neuronal structure, function, and behaviors associated with these regions. We recently demonstrated a basal sex difference in- and differential effects of stress on- microglial activation in medial prefrontal cortex (mPFC). The resident immune cells of the brain, microglia are implicated in synaptic and dendritic plasticity, and cognitive-behavioral function. Here, we examined the effects of acute (3h/day, 1 day) and chronic (3h/day, 10 days) restraint stress on microglial density and morphology, as well as immune factor expression in orbitofrontal cortex (OFC), basolateral amygdala (BLA), and dorsal hippocampus (DHC) in male and female rats. Microglia were visualized, classified based on their morphology, and stereologically counted. Microglia-associated transcripts (CD40, iNOS, Arg1, CX3CL1, CX3CR1, CD200, and CD200R) were assessed in brain punches from each region. Expression of genes linked with cellular stress, neuroimmune state, and neuron-microglia communication varied between unstressed male and female rats in a region-specific manner. In OFC, chronic stress upregulated a wider variety of immune factors in females than in males. Acute stress increased microglia-associated transcripts in BLA in males, whereas chronic stress altered immune factor expression in BLA more broadly in females. In DHC, chronic stress increased immune factor expression in males but not females. Moreover, acute and chronic stress differentially affected microglial morphological activation state in male and female rats across all brain regions investigated. In males, chronic stress altered microglial activation in a pattern consistent with microglial involvement in stress

  19. Behavioral stress alters corticolimbic microglia in a sex- and brain region-specific manner

    Science.gov (United States)

    Bollinger, Justin L.; Collins, Kaitlyn E.; Patel, Rushi

    2017-01-01

    Women are more susceptible to numerous stress-linked psychological disorders (e.g., depression) characterized by dysfunction of corticolimbic brain regions critical for emotion regulation and cognitive function. Although sparsely investigated, a number of studies indicate sex differences in stress effects on neuronal structure, function, and behaviors associated with these regions. We recently demonstrated a basal sex difference in- and differential effects of stress on- microglial activation in medial prefrontal cortex (mPFC). The resident immune cells of the brain, microglia are implicated in synaptic and dendritic plasticity, and cognitive-behavioral function. Here, we examined the effects of acute (3h/day, 1 day) and chronic (3h/day, 10 days) restraint stress on microglial density and morphology, as well as immune factor expression in orbitofrontal cortex (OFC), basolateral amygdala (BLA), and dorsal hippocampus (DHC) in male and female rats. Microglia were visualized, classified based on their morphology, and stereologically counted. Microglia-associated transcripts (CD40, iNOS, Arg1, CX3CL1, CX3CR1, CD200, and CD200R) were assessed in brain punches from each region. Expression of genes linked with cellular stress, neuroimmune state, and neuron-microglia communication varied between unstressed male and female rats in a region-specific manner. In OFC, chronic stress upregulated a wider variety of immune factors in females than in males. Acute stress increased microglia-associated transcripts in BLA in males, whereas chronic stress altered immune factor expression in BLA more broadly in females. In DHC, chronic stress increased immune factor expression in males but not females. Moreover, acute and chronic stress differentially affected microglial morphological activation state in male and female rats across all brain regions investigated. In males, chronic stress altered microglial activation in a pattern consistent with microglial involvement in stress

  20. Regional differences in gene expression and promoter usage in aged human brains

    KAUST Repository

    Pardo, Luba M.; Rizzu, Patrizia; Francescatto, Margherita; Vitezic, Morana; Leday, Gwenaë l G.R.; Sanchez, Javier Simon; Khamis, Abdullah M.; Takahashi, Hazuki; van de Berg, Wilma D.J.; Medvedeva, Yulia A.; van de Wiel, Mark A.; Daub, Carsten O.; Carninci, Piero; Heutink, Peter

    2013-01-01

    To characterize the promoterome of caudate and putamen regions (striatum), frontal and temporal cortices, and hippocampi from aged human brains, we used high-throughput cap analysis of gene expression to profile the transcription start sites

  1. Reversible and regionally selective downregulation of brain cannabinoid CB1 receptors in chronic daily cannabis smokers.

    Science.gov (United States)

    Hirvonen, J; Goodwin, R S; Li, C-T; Terry, G E; Zoghbi, S S; Morse, C; Pike, V W; Volkow, N D; Huestis, M A; Innis, R B

    2012-06-01

    Chronic cannabis (marijuana, hashish) smoking can result in dependence. Rodent studies show reversible downregulation of brain cannabinoid CB(1) (cannabinoid receptor type 1) receptors after chronic exposure to cannabis. However, whether downregulation occurs in humans who chronically smoke cannabis is unknown. Here we show, using positron emission tomography imaging, reversible and regionally selective downregulation of brain cannabinoid CB(1) receptors in human subjects who chronically smoke cannabis. Downregulation correlated with years of cannabis smoking and was selective to cortical brain regions. After ∼4 weeks of continuously monitored abstinence from cannabis on a secure research unit, CB(1) receptor density returned to normal levels. This is the first direct demonstration of cortical cannabinoid CB(1) receptor downregulation as a neuroadaptation that may promote cannabis dependence in human brain.

  2. What is the nature of causality in the brain? - Inherently probabilistic. Comment on "Foundational perspectives on causality in large-scale brain networks" by M. Mannino and S.L. Bressler

    Science.gov (United States)

    Dhamala, Mukesh

    2015-12-01

    Understanding cause-and-effect (causal) relations from observations concerns all sciences including neuroscience. Appropriately defining causality and its nature, though, has been a topic of active discussion for philosophers and scientists for centuries. Although brain research, particularly functional neuroimaging research, is now moving rapidly beyond identification of brain regional activations towards uncovering causal relations between regions, the nature of causality has not be been thoroughly described and resolved. In the current review article [1], Mannino and Bressler take us on a beautiful journey into the history of the work on causality and make a well-reasoned argument that the causality in the brain is inherently probabilistic. This notion is consistent with brain anatomy and functions, and is also inclusive of deterministic cases of inputs leading to outputs in the brain.

  3. Brain regions with mirror properties: a meta-analysis of 125 human fMRI studies.

    Science.gov (United States)

    Molenberghs, Pascal; Cunnington, Ross; Mattingley, Jason B

    2012-01-01

    Mirror neurons in macaque area F5 fire when an animal performs an action, such as a mouth or limb movement, and also when the animal passively observes an identical or similar action performed by another individual. Brain-imaging studies in humans conducted over the last 20 years have repeatedly attempted to reveal analogous brain regions with mirror properties in humans, with broad and often speculative claims about their functional significance across a range of cognitive domains, from language to social cognition. Despite such concerted efforts, the likely neural substrates of these mirror regions have remained controversial, and indeed the very existence of a distinct subcategory of human neurons with mirroring properties has been questioned. Here we used activation likelihood estimation (ALE), to provide a quantitative index of the consistency of patterns of fMRI activity measured in human studies of action observation and action execution. From an initial sample of more than 300 published works, data from 125 papers met our strict inclusion and exclusion criteria. The analysis revealed 14 separate clusters in which activation has been consistently attributed to brain regions with mirror properties, encompassing 9 different Brodmann areas. These clusters were located in areas purported to show mirroring properties in the macaque, such as the inferior parietal lobule, inferior frontal gyrus and the adjacent ventral premotor cortex, but surprisingly also in regions such as the primary visual cortex, cerebellum and parts of the limbic system. Our findings suggest a core network of human brain regions that possess mirror properties associated with action observation and execution, with additional areas recruited during tasks that engage non-motor functions, such as auditory, somatosensory and affective components. Crown Copyright © 2011. Published by Elsevier Ltd. All rights reserved.

  4. Age- and Brain Region-Specific Differences in Mitochondrial Bioenergetics in Brown Norway Rats

    Data.gov (United States)

    U.S. Environmental Protection Agency — Differences in various mitochondrial bioenergetics parameters in different brain regions in different age groups. This dataset is associated with the following...

  5. Abnormal Brain Responses to Action Observation in Complex Regional Pain Syndrome.

    Science.gov (United States)

    Hotta, Jaakko; Saari, Jukka; Koskinen, Miika; Hlushchuk, Yevhen; Forss, Nina; Hari, Riitta

    2017-03-01

    Patients with complex regional pain syndrome (CRPS) display various abnormalities in central motor function, and their pain is intensified when they perform or just observe motor actions. In this study, we examined the abnormalities of brain responses to action observation in CRPS. We analyzed 3-T functional magnetic resonance images from 13 upper limb CRPS patients (all female, ages 31-58 years) and 13 healthy, age- and sex-matched control subjects. The functional magnetic resonance imaging data were acquired while the subjects viewed brief videos of hand actions shown in the first-person perspective. A pattern-classification analysis was applied to characterize brain areas where the activation pattern differed between CRPS patients and healthy subjects. Brain areas with statistically significant group differences (q frontal gyrus, secondary somatosensory cortex, inferior parietal lobule, orbitofrontal cortex, and thalamus. Our findings indicate that CRPS impairs action observation by affecting brain areas related to pain processing and motor control. This article shows that in CRPS, the observation of others' motor actions induces abnormal neural activity in brain areas essential for sensorimotor functions and pain. These results build the cerebral basis for action-observation impairments in CRPS. Copyright © 2016 American Pain Society. Published by Elsevier Inc. All rights reserved.

  6. Associations between the self-reported frequency of hearing chemical alarms in theater and regional brain volume in Gulf War Veterans.

    Science.gov (United States)

    Chao, Linda L; Reeb, Rosemary; Esparza, Iva L; Abadjian, Linda R

    2016-03-01

    We previously reported evidence of reduced cortical gray matter (GM), white matter (WM), and hippocampal volume in Gulf War (GW) veterans with predicted exposure to low-levels of nerve agent according to the 2000 Khamisiyah plume model analysis. Because there is suggestive evidence that other nerve agent exposures may have occurred during the Gulf War, we examined the association between the self-reported frequency of hearing chemical alarms sound during deployment in the Gulf War and regional brain volume in GW veterans. Ninety consecutive GW veterans (15 female, mean age: 52±8years) participating in a VA-funded study underwent structural magnetic resonance imaging (MRI) on a 3T scanner. Freesurfer (version 5.1) was used to obtain regional measures of cortical GM, WM, hippocampal, and insula volume. Multiple linear regression was used to determine the association between the self-reported frequencies of hearing chemical alarms during the Gulf War and regional brain volume. There was an inverse association between the self-reported frequency of hearing chemical alarms sound and total cortical GM (adjusted p=0.007), even after accounting for potentially confounding demographic and clinical variables, the veterans' current health status, and other concurrent deployment-related exposures that were correlated with hearing chemical alarms. Post-hoc analyses extended the inverse relationship between the frequency of hearing chemical alarms to GM volume in the frontal (adjusted p=0.02), parietal (adjusted p=0.01), and occipital (adjusted p=0.001) lobes. In contrast, regional brain volumes were not significantly associated with predicted exposure to the Khamisiyah plume or with Gulf War Illness status defined by the Kansas or Centers for Disease Control and Prevention criteria. Many veterans reported hearing chemical alarms sound during the Gulf War. The current findings suggest that exposure to substances that triggered those chemical alarms during the Gulf War likely

  7. Theory of Mind Performance in Children Correlates with Functional Specialization of a Brain Region for Thinking about Thoughts

    Science.gov (United States)

    Gweon, Hyowon; Dodell-Feder, David; Bedny, Marina; Saxe, Rebecca

    2012-01-01

    Thinking about other people's thoughts recruits a specific group of brain regions, including the temporo-parietal junctions (TPJ), precuneus (PC), and medial prefrontal cortex (MPFC). The same brain regions were recruited when children (N = 20, 5-11 years) and adults (N = 8) listened to descriptions of characters' mental states, compared to…

  8. Global and regional brain mean diffusivity changes in patients with heart failure.

    Science.gov (United States)

    Woo, Mary A; Palomares, Jose A; Macey, Paul M; Fonarow, Gregg C; Harper, Ronald M; Kumar, Rajesh

    2015-04-01

    Heart failure (HF) patients show gray and white matter changes in multiple brain sites, including autonomic and motor coordination areas. It is unclear whether the changes represent acute or chronic tissue pathology, a distinction necessary for understanding pathological processes that can be resolved with diffusion tensor imaging (DTI)-based mean diffusivity (MD) procedures. We collected four DTI series from 16 HF (age 55.1 ± 7.8 years, 12 male) and 26 control (49.7 ± 10.8 years, 17 male) subjects with a 3.0-Tesla magnetic resonance imaging scanner. MD maps were realigned, averaged, normalized, and smoothed. Global and regional MD values from autonomic and motor coordination sites were calculated by using normalized MD maps and brain masks; group MD values and whole-brain smoothed MD maps were compared by analysis of covariance (covariates; age and gender). Global brain MD (HF vs. controls, units × 10(-6) mm(2) /sec, 1103.8 ± 76.6 vs. 1035.9 ± 69.4, P = 0.038) and regional autonomic and motor control site values (left insula, 1,085.4 ± 95.7 vs. 975.7 ± 65.4, P = 0.001; right insula, 1,050.2 ± 100.6 vs. 965.7 ± 58.4, P = 0.004; left hypothalamus, 1,419.6 ± 165.2 vs. 1,234.9 ± 136.3, P = 0.002; right hypothalamus, 1,446.5 ± 178.8 vs. 1,273.3 ± 136.9, P = 0.004; left cerebellar cortex, 889.1 ± 81.9 vs. 796.6 ± 46.8, P right cerebellar cortex, 797.8 ± 50.8 vs. 750.3 ± 27.5, P = 0.001; cerebellar deep nuclei, 1,236.1 ± 193.8 vs. 1,071.7 ± 107.1, P = 0.002) were significantly higher in HF vs. control subjects, indicating chronic tissue changes. Whole-brain comparisons showed increased MD values in HF subjects, including limbic, basal-ganglia, thalamic, solitary tract nucleus, frontal, and cerebellar regions. Brain injury occurs in autonomic and motor control areas, which may contribute to deficient function in HF patients. The chronic tissue changes likely

  9. Effects of feedborne fusarium mycotoxins on brain regional neurochemistry of turkeys.

    Science.gov (United States)

    Girish, C K; MacDonald, E J; Scheinin, M; Smith, T K

    2008-07-01

    An experiment was conducted to investigate the effects of feeding grains naturally contaminated with Fusarium mycotoxins on brain regional neurochemistry of turkeys. The possible preventative effect of a poly-meric glucomannan mycotoxin adsorbent (GMA) was also determined. Forty-five 1-d-old male turkey poults were fed wheat-, corn-, and soybean meal-based diets up to wk 6, formulated with control grains, contaminated grains, or contaminated grains + 0.2% GMA. Deoxynivalenol was the major contaminant, and the concentrations were 2.2 and 3.3 mg/kg of feed during starter and grower phases, respectively. Concentrations of brain monoamine neurotransmitters and metabolites were measured in discrete regions of the brain including the pons, hypothalamus, and cortex by HPLC with electrochemical detection. Neurotransmitters and metabolites analyzed included norepinephrine, dopamine, 3,4-dihydroxyphenylacetic acid, serotonin (5-hydroxytryptamine, 5-HT), and 5-hydroxyindoleacetic acid (5-HIAA). The concentration of 5-HIAA and the 5-HIAA:5-HT-ratio were significantly decreased in pons after feeding contaminated grains. Dietary supplementation with GMA prevented these effects. In the pons, a significant positive correlation (r = 0.52, P effects on the concentrations of neurotransmitters and metabolites in hypothalamus and cortex. It was concluded that consumption of grains naturally contaminated with Fusarium mycotoxins adversely altered the pons serotonergic system of turkeys. Supplementation with GMA partially inhibited these effects.

  10. Regional distribution of TL-201 in the brain and spinal cord after injection into the cerebrospinal fluid: Imaging of brain tumors

    International Nuclear Information System (INIS)

    Woo, D.V.; Rubertone, J.; Vincent, S.; Brady, L.W. Jr.

    1986-01-01

    Radiotracers are typically employed to evaluate the brain ventricular space; however, there are no agents designed to be taken up into specific neuronal regions after injection into the cerebrospinal fluids (CSF). The authors report studies in which T1-201 was stereotaxically administered into the lateral or fourth ventricles of Sprague-Dawley rats. Brains were removed (n = 42) 2-6 hours after injection and sectioned for apposition to autoradiographic film. Specific uptake was observed in active neurons of the diencephalon, mesencephalon, cerebellum, brain stem, and spinal gray matter. Astrocytoma cell implants into the caudate nucleus of Sprague-Dawley rats induced histologically confirmed brain tumors (n = 5). Significant localization of T1-201 was observed in the tumor 4 hours after injection into the lateral ventricle. These findings suggest that T1-201 may be useful for delineating specific neuronal function via CSF circulation and for imaging actively growing brain tumors

  11. Brain region's relative proximity as marker for Alzheimer's disease based on structural MRI

    DEFF Research Database (Denmark)

    Erleben, Lene Lillemark; Sørensen, Lauge Emil; Pai, Akshay Sadananda Uppinakudru

    2014-01-01

    BACKGROUND:Alzheimer's disease (AD) is a progressive, incurable neurodegenerative disease and the most common type of dementia. It cannot be prevented, cured or drastically slowed, even though AD research has increased in the past 5-10 years. Instead of focusing on the brain volume or on the single...... brain structures like hippocampus, this paper investigates the relationship and proximity between regions in the brain and uses this information as a novel way of classifying normal control (NC), mild cognitive impaired (MCI), and AD subjects.METHODS:A longitudinal cohort of 528 subjects (170 NC, 240...... to whole brain and hippocampus volume.RESULTS:We found that both our markers was able to significantly classify the subjects. The surface connectivity marker showed the best results with an area under the curve (AUC) at 0.877 (p...

  12. Types of traumatic brain injury and regional cerebral blood flow assessed by 99mTc-HMPAO SPECT.

    Science.gov (United States)

    Yamakami, I; Yamaura, A; Isobe, K

    1993-01-01

    To investigate the relationship between focal and diffuse traumatic brain injury (TBI) and regional cerebral blood flow (rCBF), rCBF changes in the first 24 hours post-trauma were studied in 12 severe head trauma patients using single photon emission computed tomography (SPECT) with 99mtechnetium-hexamethyl propyleneamine oxime. Patients were classified as focal or diffuse TBI based on x-ray computed tomographic (X-CT) findings and neurological signs. In six patients with focal damage, SPECT demonstrated 1) perfusion defect (focal severe ischemia) in the brain region larger than the brain contusion by X-CT, 2) hypoperfusion (focal CBF reduction) in the brain region without abnormality by X-CT, and 3) localized hyperperfusion (focal CBF increase) in the surgically decompressed brain after decompressive craniectomy. Focal damage may be associated with a heterogeneous CBF change by causing various focal CBF derangements. In six patients with diffuse damage, SPECT revealed hypoperfusion in only one patient. Diffuse damage may be associated with a homogeneous CBF change by rarely causing focal CBF derangements. The type of TBI, focal or diffuse, determines the type of CBF change, heterogeneous or homogeneous, in the acute severe head trauma patient.

  13. Types of traumatic brain injury and regional cerebral blood flow assessed by 99mTc-HMPAO SPECT

    International Nuclear Information System (INIS)

    Yamakami, Iwao; Yamaura, Akira; Isobe, Katsumi

    1993-01-01

    To investigate the relationship between focal and diffuse traumatic brain injury (TBI) and regional cerebral blood flow (rCBF), rCBF changes in the first 24 hours post-trauma were studied in 12 severe head trauma patients using single photon emission computed tomography (SPECT) with 99m technetium-hexamethyl propyleneamine oxime (HMPAO). Patients were classified as focal or diffuse TBI based on x-ray computed tomographic (X-CT) findings and neurological signs. In six patients with focal damage, SPECT demonstrated: 1) perfusion defect (focal severe ischemia) in the brain region larger than the brain contusion by X-CT, 2) hypoperfusion (focal CBF reduction) in the brain region without abnormality by X-CT, and 3) localized hyperperfusion (focal CBF increase) in the surgically decompressed brain after decompressive craniectomy. Focal damage may be associated with a heterogeneous CBF change by causing various focal CBF derangements. In six patients with diffuse damage, SPECT revealed hypoperfusion in only one patient. Diffuse damage may be associated with a homogeneous CBF change by rarely causing focal CBF derangements. The type of TBI, focal or diffuse, determines the type of CBF change, heterogeneous or homogeneous, in the acute severe head trauma patient. (author)

  14. Brain regional distributions of the minor and trace elements, Na, Mg, Cl, K, Mn, Zn, Rb and Br, in young and aged mice

    International Nuclear Information System (INIS)

    Amano, R.; Oishi, S.; Ishie, M.; Kimura, M.

    2001-01-01

    Brain regional cerebral concentrations of minor and trace elements, Na, Mg, Cl, K, Mn, Zn, Rb and Br were determined in young and aged mice, by instrumental neutron activation analysis for small amounts of regional (corpus striatum, cerebellum, cerebral cortex, hippocampus, midbrain, pons and medulla olfactory bulb) samples. Significant age-related differences were found for Mn concentration in all brain regions: The Mn concentration of the young brain was higher than those of aged brain, in addition, Zn was distributed heterogeneously, and highly concentrated in cerebral cortex and hippocampus regions in both young and aged mice. These results suggest that, in the aged brain, Mn is required less than in the young brain, on the other hand, Zn is required equally in both young and aged brains. (author)

  15. High-resolution temporal and regional mapping of MAPT expression and splicing in human brain development.

    Science.gov (United States)

    Hefti, Marco M; Farrell, Kurt; Kim, SoongHo; Bowles, Kathryn R; Fowkes, Mary E; Raj, Towfique; Crary, John F

    2018-01-01

    The microtubule associated protein tau plays a critical role in the pathogenesis of neurodegenerative disease. Recent studies suggest that tau also plays a role in disorders of neuronal connectivity, including epilepsy and post-traumatic stress disorder. Animal studies have shown that the MAPT gene, which codes for the tau protein, undergoes complex pre-mRNA alternative splicing to produce multiple isoforms during brain development. Human data, particularly on temporal and regional variation in tau splicing during development are however lacking. In this study, we present the first detailed examination of the temporal and regional sequence of MAPT alternative splicing in the developing human brain. We used a novel computational analysis of large transcriptomic datasets (total n = 502 patients), quantitative polymerase chain reaction (qPCR) and western blotting to examine tau expression and splicing in post-mortem human fetal, pediatric and adult brains. We found that MAPT exons 2 and 10 undergo abrupt shifts in expression during the perinatal period that are unique in the canonical human microtubule-associated protein family, while exon 3 showed small but significant temporal variation. Tau isoform expression may be a marker of neuronal maturation, temporally correlated with the onset of axonal growth. Immature brain regions such as the ganglionic eminence and rhombic lip had very low tau expression, but within more mature regions, there was little variation in tau expression or splicing. We thus demonstrate an abrupt, evolutionarily conserved shift in tau isoform expression during the human perinatal period that may be due to tau expression in maturing neurons. Alternative splicing of the MAPT pre-mRNA may play a vital role in normal brain development across multiple species and provides a basis for future investigations into the developmental and pathological functions of the tau protein.

  16. A novel PET imaging protocol identifies seizure-induced regional overactivity of P-glycoprotein at the blood-brain barrier

    Science.gov (United States)

    Bankstahl, Jens P.; Bankstahl, Marion; Kuntner, Claudia; Stanek, Johann; Wanek, Thomas; Meier, Martin; Ding, Xiao-Qi; Müller, Markus; Langer, Oliver; Löscher, Wolfgang

    2013-01-01

    About one third of epilepsy patients are pharmacoresistant. Overexpression of P-glycoprotein and other multidrug transporters at the blood-brain barrier is thought to play an important role in drug-refractory epilepsy. Thus, quantification of regionally different P-glycoprotein activity in the brain in vivo is essential to identify P-glycoprotein overactivity as the relevant mechanism for drug-resistance in an individual patient. Using the radiolabeled P-glycoprotein substrate (R)-[11C]verapamil and different doses of co-administered tariquidar, which is an inhibitor of P-glycoprotein, we evaluated whether small-animal positron emission tomography (PET) can quantify regional changes in transporter function in the rat brain at baseline and 48 h after a pilocarpine-induced status epilepticus. P-glycoprotein expression was additionally quantified by immunohistochemistry. To reveal putative seizure-induced changes in blood-brain barrier integrity, we performed gadolinium-enhanced magnetic resonance scans on a 7.0 Tesla small-animal scanner. Before P-glycoprotein modulation, brain uptake of (R)-[11C]verapamil was low in all regions investigated in control and post-status epilepticus rats. After administration of 3 mg/kg tariquidar, which inhibits P-glycoprotein only partially, we observed increased regional differentiation in brain activity uptake in post-status epilepticus versus control rats, which diminished after maximal P-glycoprotein inhibition. Regional increases in the efflux rate constant k2, but not in distribution volume VT or influx rate constant K1, correlated significantly with increases in P-glycoprotein expression measured by immunohistochemistry. This imaging protocol proves to be suitable to detect seizure-induced regional changes in P-glycoprotein activity and is readily applicable to humans, with the aim to detect relevant mechanisms of pharmacoresistance in epilepsy in vivo. PMID:21677164

  17. Neuron-Enriched Gene Expression Patterns are Regionally Anti-Correlated with Oligodendrocyte-Enriched Patterns in the Adult Mouse and Human Brain.

    Science.gov (United States)

    Tan, Powell Patrick Cheng; French, Leon; Pavlidis, Paul

    2013-01-01

    An important goal in neuroscience is to understand gene expression patterns in the brain. The recent availability of comprehensive and detailed expression atlases for mouse and human creates opportunities to discover global patterns and perform cross-species comparisons. Recently we reported that the major source of variation in gene transcript expression in the adult normal mouse brain can be parsimoniously explained as reflecting regional variation in glia to neuron ratios, and is correlated with degree of connectivity and location in the brain along the anterior-posterior axis. Here we extend this investigation to two gene expression assays of adult normal human brains that consisted of over 300 brain region samples, and perform comparative analyses of brain-wide expression patterns to the mouse. We performed principal components analysis (PCA) on the regional gene expression of the adult human brain to identify the expression pattern that has the largest variance. As in the mouse, we observed that the first principal component is composed of two anti-correlated patterns enriched in oligodendrocyte and neuron markers respectively. However, we also observed interesting discordant patterns between the two species. For example, a few mouse neuron markers show expression patterns that are more correlated with the human oligodendrocyte-enriched pattern and vice-versa. In conclusion, our work provides insights into human brain function and evolution by probing global relationships between regional cell type marker expression patterns in the human and mouse brain.

  18. Mercury distribution and speciation in different brain regions of beluga whales (Delphinapterus leucas)

    International Nuclear Information System (INIS)

    Ostertag, Sonja K.; Stern, Gary A.; Wang, Feiyue; Lemes, Marcos; Chan, Hing Man

    2013-01-01

    The toxicokinetics of mercury (Hg) in key species of Arctic ecosystem are poorly understood. We sampled five brain regions (frontal lobe, temporal lobe, cerebellum, brain stem and spinal cord) from beluga whales (Delphinapterus leucas) harvested in 2006, 2008, and 2010 from the eastern Beaufort Sea, Canada, and measured total Hg (HgT) and total selenium (SeT) by inductively coupled plasma mass spectrometry (ICP-MS), mercury analyzer or cold vapor atomic absorption spectrometry, and the chemical forms using a high performance liquid chromatography ICP-MS. At least 14% of the beluga whales had HgT concentrations higher than the levels of observable adverse effect (6.0 mg kg −1 wet weight (ww)) in primates. The concentrations of HgT differed between brain regions; median concentrations (mg kg −1 ww) were 2.34 (0.06 to 22.6, 81) (range, n) in temporal lobe, 1.84 (0.12 to 21.9, 77) in frontal lobe, 1.84 (0.05 to 16.9, 83) in cerebellum, 1.25 (0.02 to 11.1, 77) in spinal cord and 1.32 (0.13 to 15.2, 39) in brain stem. Total Hg concentrations in the cerebellum increased with age (p −1 ww) was positively associated with HgT concentration, and the percent MeHg (4 to 109%) decreased exponentially with increasing HgT concentration in the spinal cord, cerebellum, frontal lobe and temporal lobe. There was a positive association between SeT and HgT in all brain regions (p < 0.05) suggesting that Se may play a role in the detoxification of Hg in the brain. The concentration of HgT in the cerebellum was significantly associated with HgT in other organs. Therefore, HgT concentrations in organs that are frequently sampled in bio-monitoring studies could be used to estimate HgT concentrations in the cerebellum, which is the target organ of MeHg toxicity. - Highlights: • Mercury concentrations were highest in the temporal lobe of beluga whales. • Selenium and mercury concentrations were strongly correlated. • Total mercury concentrations in the cerebellum increased with

  19. Multivoxel 1H-MR spectroscopy in evaluating perienhancement region of brain tumors

    International Nuclear Information System (INIS)

    Xu Maosheng; Pan Zhiyong; Cao Zhijian; Wang Wei; Zheng Meijun; Ni Guibao

    2003-01-01

    Objective: To investigate the predictive value of multivoxel proton magnetic resonance spectroscopy (MRS) in evaluating the metabolic changes in perienhancement area of brain tumors. Methods: Fifty-one intracranial tumor patients were recruited in this study with 24 astrocytomas [grade II(8), III(7), IV(9)], 15 metastases, and 12 meningiomas. Multivoxel proton MRS was performed on a 1.5 TMR scanner using point-resolved spectroscopy (PRESS) sequence with TE of 144 ms and TR of 1000 ms. Spectra of three voxels were taken from A) enhanced, solid part of the tumor, B) perienhancement region (PER, with T 2 hyperintense areas), and C) corresponding contralateral normal appearing white matter, and those regions were evaluated in every patients. Fitted areas in the spectrum for N-acetylaspartate (NAA), choline (Cho), creatine (Cr), lipid/ lactate, and myo-Inositol (mI) metabolite peaks were measured and NAA/Cho, NAA/Cr, Cho/Cho (normal), Cho/Cr (n) ratios were calculated for each voxel (0.562 cm 3 in size). One way ANOVA (SPSS 11.0 for windows, Chicago, Ill.) was used for statistical analysis in metabolic ratio's difference among the brain tumors. Results: In voxel A (MRS from the solid enhanced part of the lesion), the ratios of NAA/Cho and Cho/Cho (n) changed significantly by comparing with that of normal control brain tissues, but there was no significant difference among gliomas, metastases, and meningiomas (P>0.05). On the contrary, in voxel B of MRS from perienhancement region, NAA/Cho, Cho/Cho (n), and Cho/Cr (n) ratios revealed strong correlations between metabolite concentrations and tumor types, allowing the differentiation of glial tumors from both metastases and meningiomas (P<0.05). The mean values of PER for glial tumor, metastasis, and meningiomas were 0.89, 1.31, and 1.32 for NAA/Cho; 1.54, 1.78, and 1.87 for NAA/Cr; 1.47, 1.01, and 0.96 for Cho/Cho (n); and 1.75, 1.13 and, 1.21 for Cho/Cr (n), respectively. Conclusion: Evaluation of brain tumors and

  20. Molecular regionalization of the developing amphioxus neural tube challenges major partitions of the vertebrate brain.

    Science.gov (United States)

    Albuixech-Crespo, Beatriz; López-Blanch, Laura; Burguera, Demian; Maeso, Ignacio; Sánchez-Arrones, Luisa; Moreno-Bravo, Juan Antonio; Somorjai, Ildiko; Pascual-Anaya, Juan; Puelles, Eduardo; Bovolenta, Paola; Garcia-Fernàndez, Jordi; Puelles, Luis; Irimia, Manuel; Ferran, José Luis

    2017-04-01

    All vertebrate brains develop following a common Bauplan defined by anteroposterior (AP) and dorsoventral (DV) subdivisions, characterized by largely conserved differential expression of gene markers. However, it is still unclear how this Bauplan originated during evolution. We studied the relative expression of 48 genes with key roles in vertebrate neural patterning in a representative amphioxus embryonic stage. Unlike nonchordates, amphioxus develops its central nervous system (CNS) from a neural plate that is homologous to that of vertebrates, allowing direct topological comparisons. The resulting genoarchitectonic model revealed that the amphioxus incipient neural tube is unexpectedly complex, consisting of several AP and DV molecular partitions. Strikingly, comparison with vertebrates indicates that the vertebrate thalamus, pretectum, and midbrain domains jointly correspond to a single amphioxus region, which we termed Di-Mesencephalic primordium (DiMes). This suggests that these domains have a common developmental and evolutionary origin, as supported by functional experiments manipulating secondary organizers in zebrafish and mice.

  1. Pain sensitivity is inversely related to regional grey matter density in the brain.

    Science.gov (United States)

    Emerson, Nichole M; Zeidan, Fadel; Lobanov, Oleg V; Hadsel, Morten S; Martucci, Katherine T; Quevedo, Alexandre S; Starr, Christopher J; Nahman-Averbuch, Hadas; Weissman-Fogel, Irit; Granovsky, Yelena; Yarnitsky, David; Coghill, Robert C

    2014-03-01

    Pain is a highly personal experience that varies substantially among individuals. In search of an anatomical correlate of pain sensitivity, we used voxel-based morphometry to investigate the relationship between grey matter density across the whole brain and interindividual differences in pain sensitivity in 116 healthy volunteers (62 women, 54 men). Structural magnetic resonance imaging (MRI) and psychophysical data from 10 previous functional MRI studies were used. Age, sex, unpleasantness ratings, scanner sequence, and sensory testing location were added to the model as covariates. Regression analysis of grey matter density across the whole brain and thermal pain intensity ratings at 49°C revealed a significant inverse relationship between pain sensitivity and grey matter density in bilateral regions of the posterior cingulate cortex, precuneus, intraparietal sulcus, and inferior parietal lobule. Unilateral regions of the left primary somatosensory cortex also exhibited this inverse relationship. No regions showed a positive relationship to pain sensitivity. These structural variations occurred in areas associated with the default mode network, attentional direction and shifting, as well as somatosensory processing. These findings underscore the potential importance of processes related to default mode thought and attention in shaping individual differences in pain sensitivity and indicate that pain sensitivity can potentially be predicted on the basis of brain structure. Copyright © 2013 International Association for the Study of Pain. Published by Elsevier B.V. All rights reserved.

  2. Regional specificity in deltamethrin induced cytochrome P450 expression in rat brain

    International Nuclear Information System (INIS)

    Yadav, Sanjay; Johri, Ashu; Dhawan, Alok; Seth, Prahlad K.; Parmar, Devendra

    2006-01-01

    Oral administration of deltamethrin (5 mg/kg x 7 or 15 or 21 days) was found to produce a time-dependent increase in the mRNA expression of xenobiotic metabolizing cytochrome P450 1A1 (CYP1A1), 1A2 and CYP2B1, 2B2 isoenzymes in rat brain. RT-PCR studies further showed that increase in the mRNA expression of these CYP isoenzymes observed after 21 days of exposure was region specific. Hippocampus exhibited maximum increase in the mRNA expression of CYP1A1, which was followed by pons-medulla, cerebellum and hypothalamus. The mRNA expression of CYP2B1 also exhibited maximum increase in the hypothalamus and hippocampus followed by almost similar increase in midbrain and cerebellum. In contrast, mRNA expression of CYP1A2 and CYP2B2, the constitutive isoenzymes exhibited relatively higher increase in pons-medulla, cerebellum and frontal cortex. Immunoblotting studies carried out with polyclonal antibody raised against rat liver CYP1A1/1A2 or CYP2B1/2B2 isoenzymes also showed increase in immunoreactivity comigrating with CYP1A1/1A2 or 2B1/2B2 in the microsomal fractions isolated from hippocampus, hypothalamus and cerebellum of rat treated with deltamethrin. Though the exact relationship of the xenobiotic metabolizing CYPs with the physiological function of the brain is yet to be clearly understood, the increase in the mRNA expression of the CYPs in the brain regions that regulate specific brain functions affected by deltamethrin have further indicated that modulation of these CYPs could be associated with the various endogenous functions of the brain

  3. Brain perfusion single photon emission computed tomography in major psychiatric disorders: From basics to clinical practice

    International Nuclear Information System (INIS)

    Santra, Amburanjan; Kumar, Rakesh

    2014-01-01

    Brain single photon emission computed tomography (SPECT) is a well-established and reliable method to assess brain function through measurement of regional cerebral blood flow (rCBF). It can be used to define a patient's pathophysiological status when neurological or psychiatric symptoms cannot be explained by anatomical neuroimaging findings. Though there is ample evidence validating brain SPECT as a technique to track human behavior and correlating psychiatric disorders with dysfunction of specific brain regions, only few psychiatrists have adopted brain SPECT in routine clinical practice. It can be utilized to evaluate the involvement of brain regions in a particular patient, to individualize treatment on basis of SPECT findings, to monitor the treatment response and modify treatment, if necessary. In this article, we have reviewed the available studies in this regard from existing literature and tried to present the evidence for establishing the clinical role of brain SPECT in major psychiatric illnesses

  4. Recurrent activity in higher order, modality non-specific brain regions

    DEFF Research Database (Denmark)

    Lou, Hans Olav Christensen; Joensson, Morten; Biermann-Ruben, Katja

    2011-01-01

    It has been proposed that the workings of the brain are mainly intrinsically generated recurrent neuronal activity, with sensory inputs as modifiers of such activity in both sensory and higher order modality non-specific regions. This is supported by the demonstration of recurrent neuronal activity...... in the visual system as a response to visual stimulation. In contrast recurrent activity has never been demonstrated before in higher order modality non-specific regions. Using magneto-encephalography and Granger causality analysis, we tested in a paralimbic network the hypothesis that stimulation may enhance...... causal recurrent interaction between higher-order, modality non-specific regions. The network includes anterior cingulate/medial prefrontal and posterior cingulate/medial parietal cortices together with pulvinar thalami, a network known to be effective in autobiographic memory retrieval and self...

  5. Brain regional α-[11C]methyl-L-tryptophan trapping, used as an index of 5-HT synthesis, in healthy adults: absence of an age effect

    International Nuclear Information System (INIS)

    Rosa-Neto, Pedro; Benkelfat, Chawki; Leyton, Marco; Sakai, Yojiro; Morais, Jose A.; Diksic, Mirko

    2007-01-01

    Previous functional neuroimaging studies suggest that selective aspects of the brain serotonin (5-HT) system change during the aging process. Here, we assessed the effects of aging on the brain regional α-[ 11 C]methyl-L-tryptophan (α-[ 11 C]MTrp) trapping rate constant (K*; μl.g -1 .min -1 ), which, with certain assumptions, could be taken as a proxy of 5-HT synthesis. Thirty-six healthy right-handed subjects had positron emission tomography (PET) scans following injection with α-[ 11 C]MTrp [18 males aged 46.6 ± 22.2 years (range 20-80 years) and 18 females aged 33.0 ± 15.5 years (range 20-80 years)]. The trapping rate constant, K*, was calculated with the graphical method for irreversible ligands using the sinus-venous input function. A priori selected volumes of interest (VOIs) were defined using an automatic algorithm. VOI analysis showed no correlation between age and brain regional K* values. As reported by others, significant age-related reductions of gray matter were observed in the thalamus and frontal and cingulate cortices; even with partial volume correction there was still no significant relationship between K* and age. Further exploratory SPM voxelwise correlation between age and α-[ 11 C]MTrp trapping, using p = 0.05 (uncorrected), as well as voxel-based morphometry, was in agreement with the VOI analysis. The dissociation between age-related changes in brain anatomy and this index of serotonin synthesis suggests independent mechanisms underlying the normal aging process. (orig.)

  6. Regional distribution of enkephalinase in rat brain by autoradiography

    International Nuclear Information System (INIS)

    Waksman, G.; Hamel, E.; Besselievre, R.; Fournie-Zaluski, M.C.; Roques, B.P.; Bouboutou, R.

    1984-01-01

    The first visualization of enkephalinase (neutral metalloendopeptidase, E.C.3.4.24.11) in rat brain was obtained by autoradiography, using a new tritiated inhibitor: [ 3 H]N-[(R, S) 3-(N-hydroxy) carboxamido-2-benzyl propanoyl]-glycine ( 3 H-HCBP-Gly). The preliminary analysis of sections clearly showed a discrete localization of enkephalinase in enkephalin enriched regions, such as caudate nucleus, putamen, globus pallidus, and substantia nigra. Moreover 3 H-HCBP-Gly binding also occured in choroid plexus and spinal cord [fr

  7. Toward defining deep brain stimulation targets in MNI space: A subcortical atlas based on multimodal MRI, histology and structural connectivity.

    Science.gov (United States)

    Ewert, Siobhan; Plettig, Philip; Li, Ningfei; Chakravarty, M Mallar; Collins, D Louis; Herrington, Todd M; Kühn, Andrea A; Horn, Andreas

    2018-04-15

    Three-dimensional atlases of subcortical brain structures are valuable tools to reference anatomy in neuroscience and neurology. For instance, they can be used to study the position and shape of the three most common deep brain stimulation (DBS) targets, the subthalamic nucleus (STN), internal part of the pallidum (GPi) and ventral intermediate nucleus of the thalamus (VIM) in spatial relationship to DBS electrodes. Here, we present a composite atlas based on manual segmentations of a multimodal high resolution brain template, histology and structural connectivity. In a first step, four key structures were defined on the template itself using a combination of multispectral image analysis and manual segmentation. Second, these structures were used as anchor points to coregister a detailed histological atlas into standard space. Results show that this approach significantly improved coregistration accuracy over previously published methods. Finally, a sub-segmentation of STN and GPi into functional zones was achieved based on structural connectivity. The result is a composite atlas that defines key nuclei on the template itself, fills the gaps between them using histology and further subdivides them using structural connectivity. We show that the atlas can be used to segment DBS targets in single subjects, yielding more accurate results compared to priorly published atlases. The atlas will be made publicly available and constitutes a resource to study DBS electrode localizations in combination with modern neuroimaging methods. Copyright © 2017 Elsevier Inc. All rights reserved.

  8. Radioreceptor assay of opioid peptides in selected canine brain regions

    International Nuclear Information System (INIS)

    Desiderio, D.M.; Takeshita, H.

    1985-01-01

    A radioreceptor assay using the opioid delta receptor-preferring ligand D- 2 ala, D- 5 leu leucine enkephalin ( 3 H-DADL) and the broader-specificity ligand 3 H-etorphine was used to measure five HPLC-purified neuropeptide fractions derived from the peptide-rich fraction of tissue homogenates of nine anatomical regions of the canine brain. The receptoractive peptides studied were methionine enkephalin, alpha-neo-endorphin, dynorphin 1-8, methionine enkephalin-Arg-Phe, and leucine enkephalin. These peptides derive from two larger precursors: proenkephalin A, which contains methionine enkephalin, leucine enkephalin, methionine enkephalin-Arg-Phe; and proenkephalin B, which contains alpha-neo-endorphin and dynorphin 1-8. Receptoractive peptides were measured in the peptide-rich fraction derived from homogenates of canine hypothalamus, pituitary, caudate nucleus, amygdala, hippocampus, mid-brain, thalamus, pons-medulla, and cortex

  9. Brain tissue- and region-specific abnormalities on volumetric MRI scans in 21 patients with Bardet-Biedl syndrome (BBS

    Directory of Open Access Journals (Sweden)

    Johnston Jennifer

    2011-07-01

    Full Text Available Abstract Background Bardet-Biedl syndrome (BBS is a heterogeneous human disorder inherited in an autosomal recessive pattern, and characterized by the primary findings of obesity, polydactyly, hypogonadism, and learning and behavioural problems. BBS mouse models have a neuroanatomical phenotype consisting of third and lateral ventriculomegaly, thinning of the cerebral cortex, and reduction in the size of the corpus striatum and hippocampus. These abnormalities raise the question of whether humans with BBS have a characteristic morphologic brain phenotype. Further, although behavioral, developmental, neurological and motor defects have been noted in patients with BBS, to date, there are limited reports of brain findings in BBS. The present study represents the largest systematic evaluation for the presence of structural brain malformations and/or progressive changes, which may contribute to these functional problems. Methods A case-control study of 21 patients, most aged 13-35 years, except for 2 patients aged 4 and 8 years, who were diagnosed with BBS by clinical criteria and genetic analysis of known BBS genes, and were evaluated by qualitative and volumetric brain MRI scans. Healthy controls were matched 3:1 by age, sex and race. Statistical analysis was performed using SAS language with SAS STAT procedures. Results All 21 patients with BBS were found to have statistically significant region- and tissue-specific patterns of brain abnormalities. There was 1 normal intracranial volume; 2 reduced white matter in all regions of the brain, but most in the occipital region; 3 preserved gray matter volume, with increased cerebral cortex volume in only the occipital lobe; 4 reduced gray matter in the subcortical regions of the brain, including the caudate, putamen and thalamus, but not in the cerebellum; and 5 increased cerebrospinal fluid volume. Conclusions There are distinct and characteristic abnormalities in tissue- and region- specific volumes

  10. Sex Differences in Regional Brain Glucose Metabolism Following Opioid Withdrawal and Replacement.

    Science.gov (United States)

    Santoro, Giovanni C; Carrion, Joseph; Patel, Krishna; Vilchez, Crystal; Veith, Jennifer; Brodie, Jonathan D; Dewey, Stephen L

    2017-08-01

    Methadone and buprenorphine are currently the most common pharmacological treatments for opioid dependence. Interestingly, the clinical response to these drugs appears to be sex specific. That is, females exhibit superior therapeutic efficacy, defined as extended periods of abstinence and longer time to relapse, compared with males. However, the underlying metabolic effects of opioid withdrawal and replacement have not been examined. Therefore, using 18 FDG and microPET, we measured differences in regional brain glucose metabolism in males and females following morphine withdrawal and subsequent methadone or buprenorphine replacement. In both males and females, spontaneous opioid withdrawal altered glucose metabolism in regions associated with reward and drug dependence. Specifically, metabolic increases in the thalamus, as well as metabolic decreases in insular cortex and the periaqueductal gray, were noted. However, compared with males, females exhibited increased metabolism in the preoptic area, primary motor cortex, and the amygdala, and decreased metabolism in the caudate/putamen and medial geniculate nucleus. Methadone and buprenorphine initially abolished these changes uniformly, but subsequently produced their own regional metabolic alterations that varied by treatment and sex. Compared with sex-matched control animals undergoing spontaneous opioid withdrawal, male animals treated with methadone exhibited increased caudate/putamen metabolism, whereas buprenorphine produced increased ventral striatum and motor cortex metabolism in females, and increased ventral striatum and somatosensory cortex metabolism in males. Notably, when treatment effects were compared between sexes, methadone-treated females showed increased cingulate cortex metabolism, whereas buprenorphine-treated females showed decreased metabolism in cingulate cortex and increased metabolism in the globus pallidus. Perhaps the initial similarities in males and females underlie early therapeutic

  11. The Effects of Dietary Fat and Iron Interaction on Brain Regional Iron Contents and Stereotypical Behaviors in Male C57BL/6J Mice

    Directory of Open Access Journals (Sweden)

    Lumei Liu

    2016-07-01

    Full Text Available Adequate brain iron levels are essential for enzyme activities, myelination, and neurotransmitter synthesis in the brain. Although systemic iron deficiency has been found in genetically or dietary-induced obese subjects, the effects of obesity-associated iron dysregulation in brain regions have not been examined. The objective of this study was to examine the effect of dietary fat and iron interaction on brain regional iron contents and regional-associated behavior patterns in a mouse model. Thirty C57BL/6J male weanling mice were randomly assigned to six dietary treatment groups (n=5 with varying fat (control/high and iron (control/high/low contents. The stereotypical behaviors were measured during the 24th week. Blood, liver, and brain tissues were collected at the end of the 24th week. Brains were dissected into the hippocampus, midbrain, striatum, and thalamus regions. Iron contents and ferritin-H (FtH protein and mRNA expressions in these regions were measured. Correlations between stereotypical behaviors and brain regional iron contents were analyzed at the 5% significance level. Results showed that high-fat diet altered the stereotypical behaviors such as inactivity and total distance traveled (P<0.05. The high-fat diet altered brain iron contents and ferritin-H (FtH protein and mRNA expressions in a regional-specific manner: 1 high-fat diet significantly decreased the brain iron content in the striatum (P<0.05, but not other regions; and 2 thalamus has a more distinct change in FtH mRNA expression compared to other regions. Furthermore, high-fat diet resulted in a significant decreased total distance traveled and a significant correlation between iron content and sleeping in midbrain (P<0.05. Dietary iron also decreased brain iron content and FtH protein expression in a regionally specific manner. The effect of interaction between dietary fat and iron was observed in brain iron content and behaviors. All these findings will lay

  12. Sexual dimorphism of Broca's region: More gray matter in female brains in Brodmann areas 44 and 45.

    Science.gov (United States)

    Kurth, Florian; Jancke, Lutz; Luders, Eileen

    2017-01-02

    Although a sexual dimorphism in brain structure is generally well established, evidence for sex differences in Brodmann areas (BA) 44 and 45 is inconclusive. This may be due to the difficulty of accurately defining BA 44 and BA 45 in magnetic resonance images, given that these regions are variable in their location and extent and that they do not match well with macroanatomic landmarks. Here we set out to test for possible sex differences in the local gray matter of BA 44/45 by integrating imaging-based signal intensities with cytoarchitectonically defined tissue probabilities in a sample of 50 male and 50 female subjects. In addition to testing for sex differences with respect to left- and right-hemispheric measures of BA 44/45, we also assessed possible sex differences in BA 44/45 asymmetry. Our analyses revealed significantly larger gray matter volumes in females compared with males for BA 44 and BA 45 bilaterally. However, there was a lack of significant sex differences in BA 44/45 asymmetry. These results corroborate reports of a language-related female superiority, particularly with respect to verbal fluency and verbal memory tasks. © 2016 Wiley Periodicals, Inc. © 2016 Wiley Periodicals, Inc.

  13. Time-dependent regional brain distribution of methadone and naltrexone in the treatment of opioid addiction.

    Science.gov (United States)

    Teklezgi, Belin G; Pamreddy, Annapurna; Baijnath, Sooraj; Kruger, Hendrik G; Naicker, Tricia; Gopal, Nirmala D; Govender, Thavendran

    2018-02-14

    Opioid addiction is a serious public health concern with severe health and social implications; therefore, extensive therapeutic efforts are required to keep users drug free. The two main pharmacological interventions, in the treatment of addiction, involve management with methadone an mu (μ)-opioid agonist and treatment with naltrexone, μ-opioid, kappa (κ)-opioid and delta (δ)-opioid antagonist. MET and NAL are believed to help individuals to derive maximum benefit from treatment and undergo a full recovery. The aim of this study was to determine the localization and distribution of MET and NAL, over a 24-hour period in rodent brain, in order to investigate the differences in their respective regional brain distributions. This would provide a better understanding of the role of each individual drug in the treatment of addiction, especially NAL, whose efficacy is controversial. Tissue distribution was determined by using mass spectrometric imaging (MSI), in combination with quantification via liquid chromatography tandem mass spectrometry. MSI image analysis showed that MET was highly localized in the striatal and hippocampal regions, including the nucleus caudate, putamen and the upper cortex. NAL was distributed with high intensities in the mesocorticolimbic system including areas of the cortex, caudate putamen and ventral pallidum regions. Our results demonstrate that MET and NAL are highly localized in the brain regions with a high density of μ-receptors, the primary sites of heroin binding. These areas are strongly implicated in the development of addiction and are the major pathways that mediate brain stimulation during reward. © 2018 Society for the Study of Addiction.

  14. MAPT expression and splicing is differentially regulated by brain region: relation to genotype and implication for tauopathies

    Science.gov (United States)

    Trabzuni, Daniah; Wray, Selina; Vandrovcova, Jana; Ramasamy, Adaikalavan; Walker, Robert; Smith, Colin; Luk, Connie; Gibbs, J. Raphael; Dillman, Allissa; Hernandez, Dena G.; Arepalli, Sampath; Singleton, Andrew B.; Cookson, Mark R.; Pittman, Alan M.; de Silva, Rohan; Weale, Michael E.; Hardy, John; Ryten, Mina

    2012-01-01

    The MAPT (microtubule-associated protein tau) locus is one of the most remarkable in neurogenetics due not only to its involvement in multiple neurodegenerative disorders, including progressive supranuclear palsy, corticobasal degeneration, Parksinson's disease and possibly Alzheimer's disease, but also due its genetic evolution and complex alternative splicing features which are, to some extent, linked and so all the more intriguing. Therefore, obtaining robust information regarding the expression, splicing and genetic regulation of this gene within the human brain is of immense importance. In this study, we used 2011 brain samples originating from 439 individuals to provide the most reliable and coherent information on the regional expression, splicing and regulation of MAPT available to date. We found significant regional variation in mRNA expression and splicing of MAPT within the human brain. Furthermore, at the gene level, the regional distribution of mRNA expression and total tau protein expression levels were largely in agreement, appearing to be highly correlated. Finally and most importantly, we show that while the reported H1/H2 association with gene level expression is likely to be due to a technical artefact, this polymorphism is associated with the expression of exon 3-containing isoforms in human brain. These findings would suggest that contrary to the prevailing view, genetic risk factors for neurodegenerative diseases at the MAPT locus are likely to operate by changing mRNA splicing in different brain regions, as opposed to the overall expression of the MAPT gene. PMID:22723018

  15. Brain regional networks active during the mismatch negativity vary with paradigm.

    Science.gov (United States)

    MacLean, Shannon E; Blundon, Elizabeth G; Ward, Lawrence M

    2015-08-01

    We used independent component analysis (ICA) of high-density EEG recordings coupled with single dipole fitting to identify the dominant brain regions active during the MMN in two different versions of a passive oddball paradigm: a simple, monotic, frequency-deviant paradigm and a more complex, dichotic, frequency-deviant paradigm with deviants occurring in either ear alone or in both ears at the same time. In both paradigms we found brain regional sources in the temporal and frontal cortices active during the MMN period, consistent with some previous studies. In the simpler paradigm, the scalp-potential variance during the earlier (70-120 ms) MMN was mostly accounted for by a wide array of temporal, frontal, and parietal sources. In the more complex paradigm, however, a generator in the prefrontal cortex accounted for a substantial amount of the variance of the scalp potential during the somewhat later MMN period (120-200 ms). These findings are consistent with a more nuanced view of the MMN and its generators than has been held in the past. Copyright © 2015 Elsevier Ltd. All rights reserved.

  16. Regional differences in brain volume predict the acquisition of skill in a complex real-time strategy videogame.

    Science.gov (United States)

    Basak, Chandramallika; Voss, Michelle W; Erickson, Kirk I; Boot, Walter R; Kramer, Arthur F

    2011-08-01

    Previous studies have found that differences in brain volume among older adults predict performance in laboratory tasks of executive control, memory, and motor learning. In the present study we asked whether regional differences in brain volume as assessed by the application of a voxel-based morphometry technique on high resolution MRI would also be useful in predicting the acquisition of skill in complex tasks, such as strategy-based video games. Twenty older adults were trained for over 20 h to play Rise of Nations, a complex real-time strategy game. These adults showed substantial improvements over the training period in game performance. MRI scans obtained prior to training revealed that the volume of a number of brain regions, which have been previously associated with subsets of the trained skills, predicted a substantial amount of variance in learning on the complex game. Thus, regional differences in brain volume can predict learning in complex tasks that entail the use of a variety of perceptual, cognitive and motor processes. Copyright © 2011 Elsevier Inc. All rights reserved.

  17. A Multimodal Approach for Determining Brain Networks by Jointly Modeling Functional and Structural Connectivity

    Directory of Open Access Journals (Sweden)

    Wenqiong eXue

    2015-02-01

    Full Text Available Recent innovations in neuroimaging technology have provided opportunities for researchers to investigate connectivity in the human brain by examining the anatomical circuitry as well as functional relationships between brain regions. Existing statistical approaches for connectivity generally examine resting-state or task-related functional connectivity (FC between brain regions or separately examine structural linkages. As a means to determine brain networks, we present a unified Bayesian framework for analyzing FC utilizing the knowledge of associated structural connections, which extends an approach by Patel et al.(2006a that considers only functional data. We introduce an FC measure that rests upon assessments of functional coherence between regional brain activity identified from functional magnetic resonance imaging (fMRI data. Our structural connectivity (SC information is drawn from diffusion tensor imaging (DTI data, which is used to quantify probabilities of SC between brain regions. We formulate a prior distribution for FC that depends upon the probability of SC between brain regions, with this dependence adhering to structural-functional links revealed by our fMRI and DTI data. We further characterize the functional hierarchy of functionally connected brain regions by defining an ascendancy measure that compares the marginal probabilities of elevated activity between regions. In addition, we describe topological properties of the network, which is composed of connected region pairs, by performing graph theoretic analyses. We demonstrate the use of our Bayesian model using fMRI and DTI data from a study of auditory processing. We further illustrate the advantages of our method by comparisons to methods that only incorporate functional information.

  18. Common brain regions underlying different arithmetic operations as revealed by conjunct fMRI-BOLD activation.

    Science.gov (United States)

    Fehr, Thorsten; Code, Chris; Herrmann, Manfred

    2007-10-03

    The issue of how and where arithmetic operations are represented in the brain has been addressed in numerous studies. Lesion studies suggest that a network of different brain areas are involved in mental calculation. Neuroimaging studies have reported inferior parietal and lateral frontal activations during mental arithmetic using tasks of different complexities and using different operators (addition, subtraction, etc.). Indeed, it has been difficult to compare brain activation across studies because of the variety of different operators and different presentation modalities used. The present experiment examined fMRI-BOLD activity in participants during calculation tasks entailing different arithmetic operations -- addition, subtraction, multiplication and division -- of different complexities. Functional imaging data revealed a common activation pattern comprising right precuneus, left and right middle and superior frontal regions during all arithmetic operations. All other regional activations were operation specific and distributed in prominently frontal, parietal and central regions when contrasting complex and simple calculation tasks. The present results largely confirm former studies suggesting that activation patterns due to mental arithmetic appear to reflect a basic anatomical substrate of working memory, numerical knowledge and processing based on finger counting, and derived from a network originally related to finger movement. We emphasize that in mental arithmetic research different arithmetic operations should always be examined and discussed independently of each other in order to avoid invalid generalizations on arithmetics and involved brain areas.

  19. Regional cerebral blood flow in the patient with brain tumor

    International Nuclear Information System (INIS)

    Tsuchida, Shohei

    1993-01-01

    Regional cerebral blood flow (rCBF) was measured with xenon-enhanced CT (Xe-CT) in 21 cases of intracranial tumors (13 meningiomas, 5 gliomas, 3 metastatic brain tumors). Peritumoral edema was graded as mild, moderate or severe based on the extent of edema on CT and MRI. According to intratumoral blood flow distribution patterns, three patterns were classified as central type with relatively high blood flow at the center of the tumor, homogeneous type with an almost homogeneous blood flow distribution, and marginal type with relatively high blood flow at the periphery of the tumor. High grade astrocytoma and metastatic brain tumor showed marginal type blood flow and moderate or severe edema except in one case. Five meningiomas with severe peritumoral edema revealed marginal type blood flow and four with mild peritumoral edema showed central type blood flow, except for one case. No correlation was found between the extent of peritumoral edema and histological subtype, tumor size, location, duration of clinical history, vascularization on angiogram, and mean blood flow in the tumor. These results suggest that blood flow distribution patterns within the tumor may affect the extension of peritumoral edema. Pre- and postoperative rCBFs were evaluated with Xe-CT and IMP-SPECT in 7 cases, mean rCBF of peritumoral edema was 6.2 ml/100 g/min preoperatively, and discrepancy between rCBF on Xe-CT and that on IMP-SPECT was shown in the remote cortical region ipsilateral to the tumor. Postoperative rCBF revealed an improved blood flow in both adjacent and remote areas, suggesting that the decreased blood flow associated with brain tumors might be relieved after surgery. (author) 53 refs

  20. Rapid eye movement sleep deprivation induces an increase in acetylcholinesterase activity in discrete rat brain regions

    Directory of Open Access Journals (Sweden)

    Benedito M.A.C.

    2001-01-01

    Full Text Available Some upper brainstem cholinergic neurons (pedunculopontine and laterodorsal tegmental nuclei are involved in the generation of rapid eye movement (REM sleep and project rostrally to the thalamus and caudally to the medulla oblongata. A previous report showed that 96 h of REM sleep deprivation in rats induced an increase in the activity of brainstem acetylcholinesterase (Achase, the enzyme which inactivates acetylcholine (Ach in the synaptic cleft. There was no change in the enzyme's activity in the whole brain and cerebrum. The components of the cholinergic synaptic endings (for example, Achase are not uniformly distributed throughout the discrete regions of the brain. In order to detect possible regional changes we measured Achase activity in several discrete rat brain regions (medulla oblongata, pons, thalamus, striatum, hippocampus and cerebral cortex after 96 h of REM sleep deprivation. Naive adult male Wistar rats were deprived of REM sleep using the flower-pot technique, while control rats were left in their home cages. Total, membrane-bound and soluble Achase activities (nmol of thiocholine formed min-1 mg protein-1 were assayed photometrically. The results (mean ± SD obtained showed a statistically significant (Student t-test increase in total Achase activity in the pons (control: 147.8 ± 12.8, REM sleep-deprived: 169.3 ± 17.4, N = 6 for both groups, P<0.025 and thalamus (control: 167.4 ± 29.0, REM sleep-deprived: 191.9 ± 15.4, N = 6 for both groups, P<0.05. Increases in membrane-bound Achase activity in the pons (control: 171.0 ± 14.7, REM sleep-deprived: 189.5 ± 19.5, N = 6 for both groups, P<0.05 and soluble enzyme activity in the medulla oblongata (control: 147.6 ± 16.3, REM sleep-deprived: 163.8 ± 8.3, N = 6 for both groups, P<0.05 were also observed. There were no statistically significant differences in the enzyme's activity in the other brain regions assayed. The present findings show that the increase in Achase activity

  1. Long-term global and regional brain volume changes following severe traumatic brain injury: A longitudinal study with clinical correlates

    DEFF Research Database (Denmark)

    Sidaros, Annette; Skimminge, Arnold Jesper Møller; Liptrot, Matthew George

    2009-01-01

    with percent brain volume change (%BVC) ranging between − 0.6% and − 9.4% (mean − 4.0%). %BVC correlated significantly with injury severity, functional status at both scans, and with 1-year outcome. Moreover, %BVC improved prediction of long-term functional status over and above what could be predicted using......Traumatic brain injury (TBI) results in neurodegenerative changes that progress for months, perhaps even years post-injury. However, there is little information on the spatial distribution and the clinical significance of this late atrophy. In 24 patients who had sustained severe TBI we acquired 3D...... scan time point using SIENAX. Regional distribution of atrophy was evaluated using tensor-based morphometry (TBM). At the first scan time point, brain parenchymal volume was reduced by mean 8.4% in patients as compared to controls. During the scan interval, patients exhibited continued atrophy...

  2. Optogenetic Approaches for Mesoscopic Brain Mapping.

    Science.gov (United States)

    Kyweriga, Michael; Mohajerani, Majid H

    2016-01-01

    Recent advances in identifying genetically unique neuronal proteins has revolutionized the study of brain circuitry. Researchers are now able to insert specific light-sensitive proteins (opsins) into a wide range of specific cell types via viral injections or by breeding transgenic mice. These opsins enable the activation, inhibition, or modulation of neuronal activity with millisecond control within distinct brain regions defined by genetic markers. Here we present a useful guide to implement this technique into any lab. We first review the materials needed and practical considerations and provide in-depth instructions for acute surgeries in mice. We conclude with all-optical mapping techniques for simultaneous recording and manipulation of population activity of many neurons in vivo by combining arbitrary point optogenetic stimulation and regional voltage-sensitive dye imaging. It is our intent to make these methods available to anyone wishing to use them.

  3. Types of traumatic brain injury and regional cerebral blood flow assessed by [sup 99m]Tc-HMPAO SPECT

    Energy Technology Data Exchange (ETDEWEB)

    Yamakami, Iwao; Yamaura, Akira; Isobe, Katsumi [Chiba Univ. (Japan). School of Medicine

    1993-01-01

    To investigate the relationship between focal and diffuse traumatic brain injury (TBI) and regional cerebral blood flow (rCBF), rCBF changes in the first 24 hours post-trauma were studied in 12 severe head trauma patients using single photon emission computed tomography (SPECT) with [sup 99m]technetium-hexamethyl propyleneamine oxime (HMPAO). Patients were classified as focal or diffuse TBI based on x-ray computed tomographic (X-CT) findings and neurological signs. In six patients with focal damage, SPECT demonstrated: (1) perfusion defect (focal severe ischemia) in the brain region larger than the brain contusion by X-CT, (2) hypoperfusion (focal CBF reduction) in the brain region without abnormality by X-CT, and (3) localized hyperperfusion (focal CBF increase) in the surgically decompressed brain after decompressive craniectomy. Focal damage may be associated with a heterogeneous CBF change by causing various focal CBF derangements. In six patients with diffuse damage, SPECT revealed hypoperfusion in only one patient. Diffuse damage may be associated with a homogeneous CBF change by rarely causing focal CBF derangements. The type of TBI, focal or diffuse, determines the type of CBF change, heterogeneous or homogeneous, in the acute severe head trauma patient. (author).

  4. In vivo proton magnetic resonance spectroscopy reveals region specific metabolic responses to SIV infection in the macaque brain

    Directory of Open Access Journals (Sweden)

    Joo Chan-Gyu

    2009-06-01

    Full Text Available Abstract Background In vivo proton magnetic resonance spectroscopy (1H-MRS studies of HIV-infected humans have demonstrated significant metabolic abnormalities that vary by brain region, but the causes are poorly understood. Metabolic changes in the frontal cortex, basal ganglia and white matter in 18 SIV-infected macaques were investigated using MRS during the first month of infection. Results Changes in the N-acetylaspartate (NAA, choline (Cho, myo-inositol (MI, creatine (Cr and glutamine/glutamate (Glx resonances were quantified both in absolute terms and relative to the creatine resonance. Most abnormalities were observed at the time of peak viremia, 2 weeks post infection (wpi. At that time point, significant decreases in NAA and NAA/Cr, reflecting neuronal injury, were observed only in the frontal cortex. Cr was significantly elevated only in the white matter. Changes in Cho and Cho/Cr were similar across the brain regions, increasing at 2 wpi, and falling below baseline levels at 4 wpi. MI and MI/Cr levels were increased across all brain regions. Conclusion These data best support the hypothesis that different brain regions have variable intrinsic vulnerabilities to neuronal injury caused by the AIDS virus.

  5. Radioreceptor assay of opioid peptides in selected canine brain regions

    Energy Technology Data Exchange (ETDEWEB)

    Desiderio, D.M.; Takeshita, H.

    1985-09-01

    A radioreceptor assay using the opioid delta receptor-preferring ligand D-/sup 2/ala, D-/sup 5/leu leucine enkephalin (/sup 3/H-DADL) and the broader-specificity ligand /sup 3/H-etorphine was used to measure five HPLC-purified neuropeptide fractions derived from the peptide-rich fraction of tissue homogenates of nine anatomical regions of the canine brain. The receptoractive peptides studied were methionine enkephalin, alpha-neo-endorphin, dynorphin 1-8, methionine enkephalin-Arg-Phe, and leucine enkephalin. These peptides derive from two larger precursors: proenkephalin A, which contains methionine enkephalin, leucine enkephalin, methionine enkephalin-Arg-Phe; and proenkephalin B, which contains alpha-neo-endorphin and dynorphin 1-8. Receptoractive peptides were measured in the peptide-rich fraction derived from homogenates of canine hypothalamus, pituitary, caudate nucleus, amygdala, hippocampus, mid-brain, thalamus, pons-medulla, and cortex.

  6. Regional cerebral blood flow in various types of brain tumor. Effect of the space-occupying lesion on blood flow in brain tissue close to and remote from tumor site

    DEFF Research Database (Denmark)

    Kuroda, K; Skyhøj Olsen, T; Lassen, N A

    1982-01-01

    Regional cerebral blood flow (rCBF) was measured in 23 patients with brain tumors using the 133Xe intra-carotid injection method and a 254 channel gamma camera. The glioblastomas (4) and astrocytomas (4) all showed hyperemia in the tumor and tumor-near region. This was also seen in several...... meningiomas (4 of 7 cases) in which most of the tumor itself did not receive any isotope. Brain metastases (6) usually had a low flow in the tumor and tumor-near region. The glioblastomas tended to show markedly bending 133Xe wash-out curves pointing to pronounced heterogeneity of blood flow. Most of the flow...... maps, regardless of the tumor types, showed widespread abnormalities of rCBF not only in the tumor region but also in the region remote from the tumor. It is concluded that measurement of rCBF cannot yield accurate differential diagnostic information, but that the widespread derangement of the brain...

  7. Data-driven identification of intensity normalization region based on longitudinal coherency of 18F-FDG metabolism in the healthy brain.

    Science.gov (United States)

    Zhang, Huiwei; Wu, Ping; Ziegler, Sibylle I; Guan, Yihui; Wang, Yuetao; Ge, Jingjie; Schwaiger, Markus; Huang, Sung-Cheng; Zuo, Chuantao; Förster, Stefan; Shi, Kuangyu

    2017-02-01

    In brain 18 F-FDG PET data intensity normalization is usually applied to control for unwanted factors confounding brain metabolism. However, it can be difficult to determine a proper intensity normalization region as a reference for the identification of abnormal metabolism in diseased brains. In neurodegenerative disorders, differentiating disease-related changes in brain metabolism from age-associated natural changes remains challenging. This study proposes a new data-driven method to identify proper intensity normalization regions in order to improve separation of age-associated natural changes from disease related changes in brain metabolism. 127 female and 128 male healthy subjects (age: 20 to 79) with brain 18 F-FDG PET/CT in the course of a whole body cancer screening were included. Brain PET images were processed using SPM8 and were parcellated into 116 anatomical regions according to the AAL template. It is assumed that normal brain 18 F-FDG metabolism has longitudinal coherency and this coherency leads to better model fitting. The coefficient of determination R 2 was proposed as the coherence coefficient, and the total coherence coefficient (overall fitting quality) was employed as an index to assess proper intensity normalization strategies on single subjects and age-cohort averaged data. Age-associated longitudinal changes of normal subjects were derived using the identified intensity normalization method correspondingly. In addition, 15 subjects with clinically diagnosed Parkinson's disease were assessed to evaluate the clinical potential of the proposed new method. Intensity normalizations by paracentral lobule and cerebellar tonsil, both regions derived from the new data-driven coherency method, showed significantly better coherence coefficients than other intensity normalization regions, and especially better than the most widely used global mean normalization. Intensity normalization by paracentral lobule was the most consistent method within both

  8. Effect of cadmium exposure on lipids, lipid peroxidation and metal distribution in rat brain regions

    Energy Technology Data Exchange (ETDEWEB)

    Hussain, T; Ali, M M; Chandra, S V

    1985-01-01

    Effect of cadmium treatment on brain lipids, lipid peroxidation and distribution of Zn, Cu and Fe in rat brain regions was investigated. Adult male rats were exposed to Cd (100 ppm Cd as cadmium acetate) in drinking water for 30 days. The Cd exposure resulted in a significant decrease in the phospholipid content and an increase in the lipid peroxidation in the cerebral cortex and cerebellum. The total lipid content was not affected in any of the regions but a significant decrease in cholesterol and cerebroside contents were observed only in the cerebral cortex. A positive correlation between the increase in lipid peroxidation and decrease in the phospholipid content in the cerebral cortex and cerebellum was observed. A maximum accumulation of Cd occurred in the cerebral cortex. The Cu and Fe contents were significantly increased but the Zn levels decreased in the Cd-treated rats in all but the midbrain region. Results suggest that the increased peroxidation decomposition of structural lipids and the altered distribution of the essential trace metals in brain may play a significant role in Cd-induced neurotoxicity. 27 references, 2 tables.

  9. Stimulatory effect of the D2 antagonist sulpiride on glucose utilization in dopaminergic regions of rat brain

    Energy Technology Data Exchange (ETDEWEB)

    Pizzolato, G; Soncrant, T T; Larson, D M; Rapoport, S I

    1987-08-01

    Local cerebral glucose utilization (LCGU) was measured, using the quantitative autoradiographic (/sup 14/C)2-deoxy-D-glucose method, in 56 brain regions of 3-month-old, awake Fischer-344 rats, after intraperitoneal administration of sulpiride (SULP) 100 mg/kg. SULP, an atypical neuroleptic, is a selective antagonist of D2 dopamine receptors. LCGU was reduced in a few nondopaminergic regions at 1 h after drug administration. Thereafter, SULP progressively elevated LCGU in many other regions. At 3 h, LCGU was elevated in 23% of the regions examined, most of which are related to the CNS dopaminergic system (caudate-putamen, nucleus accumbens, olfactory tubercle, lateral habenula, median eminence, paraventricular hypothalamic nucleus). Increases of LCGU were observed also in the suprachiasmatic nucleus, lateral geniculate, and inferior olive. These effects of SULP on LCGU differ from the effects of the typical neuroleptic haloperidol, which produces widespread decreases in LCGU in the rat brain. Selective actions on different subpopulations of dopamine receptors may explain the different effects of the two neuroleptics on brain metabolism, which correspond to their different clinical and behavioral actions.

  10. Rapid transport of CCL11 across the blood-brain barrier: regional variation and importance of blood cells.

    Science.gov (United States)

    Erickson, Michelle A; Morofuji, Yoichi; Owen, Joshua B; Banks, William A

    2014-06-01

    Increased blood levels of the eotaxin chemokine C-C motif ligand 11 (CCL11) in aging were recently shown to negatively regulate adult hippocampal neurogenesis. How circulating CCL11 could affect the central nervous system (CNS) is not clear, but one possibility is that it can cross the blood-brain barrier (BBB). Here, we show that CCL11 undergoes bidirectional transport across the BBB. Transport of CCL11 from blood into whole brain (influx) showed biphasic kinetics, with a slow phase preceding a rapid phase of uptake. We found that the slow phase was explained by binding of CCL11 to cellular components in blood, whereas the rapid uptake phase was mediated by direct interactions with the BBB. CCL11, even at high doses, did not cause BBB disruption. All brain regions except striatum showed a delayed rapid-uptake phase. Striatum had only an early rapid-uptake phase, which was the fastest of any brain region. We also observed a slow but saturable transport system for CCL11 from brain to blood. C-C motif ligand 3 (CCR3), an important receptor for CCL11, did not facilitate CCL11 transport across the BBB, although high concentrations of a CCR3 inhibitor increased brain uptake without causing BBB disruption. Our results indicate that CCL11 in the circulation can access many regions of the brain outside of the neurogenic niche via transport across the BBB. This suggests that blood-borne CCL11 may have important physiologic functions in the CNS and implicates the BBB as an important regulator of physiologic versus pathologic effects of this chemokine.

  11. Brain networks that track musical structure.

    Science.gov (United States)

    Janata, Petr

    2005-12-01

    As the functional neuroimaging literature grows, it becomes increasingly apparent that music and musical activities engage diverse regions of the brain. In this paper I discuss two studies to illustrate that exactly which brain areas are observed to be responsive to musical stimuli and tasks depends on the tasks and the methods used to describe the tasks and the stimuli. In one study, subjects listened to polyphonic music and were asked to either orient their attention selectively to individual instruments or in a divided or holistic manner across multiple instruments. The network of brain areas that was recruited changed subtly with changes in the task instructions. The focus of the second study was to identify brain regions that follow the pattern of movement of a continuous melody through the tonal space defined by the major and minor keys of Western tonal music. Such an area was identified in the rostral medial prefrontal cortex. This observation is discussed in the context of other neuroimaging studies that implicate this region in inwardly directed mental states involving decisions about the self, autobiographical memory, the cognitive regulation of emotion, affective responses to musical stimuli, and familiarity judgments about musical stimuli. Together with observations that these regions are among the last to atrophy in Alzheimer disease, and that these patients appear to remain responsive to autobiographically salient musical stimuli, very early evidence is emerging from the literature for the hypothesis that the rostral medial prefrontal cortex is a node that is important for binding music with memories within a broader music-responsive network.

  12. Lutein Is Differentially Deposited across Brain Regions following Formula or Breast Feeding of Infant Rhesus Macaques.

    Science.gov (United States)

    Jeon, Sookyoung; Ranard, Katherine M; Neuringer, Martha; Johnson, Emily E; Renner, Lauren; Kuchan, Matthew J; Pereira, Suzette L; Johnson, Elizabeth J; Erdman, John W

    2018-01-01

    Lutein, a yellow xanthophyll, selectively accumulates in primate retina and brain. Lutein may play a critical role in neural and retinal development, but few studies have investigated the impact of dietary source on its bioaccumulation in infants. We explored the bioaccumulation of lutein in infant rhesus macaques following breastfeeding or formula-feeding. From birth to 6 mo of age, male and female rhesus macaques (Macaca mulatta) were either breastfed (BF) (n = 8), fed a formula supplemented with lutein, zeaxanthin, β-carotene, and lycopene (237, 19.0, 74.2, and 338 nmol/kg, supplemented formula-fed; SF) (n = 8), or fed a formula with low amounts of these carotenoids (38.6, 2.3, 21.5, and 0 nmol/kg, unsupplemented formula-fed; UF) (n = 7). The concentrations of carotenoids in serum and tissues were analyzed by HPLC. At 6 mo of age, the BF group exhibited significantly higher lutein concentrations in serum, all brain regions, macular and peripheral retina, adipose tissue, liver, and other tissues compared to both formula-fed groups (P Lutein concentrations were higher in the SF group than in the UF group in serum and all tissues, with the exception of macular retina. Lutein was differentially distributed across brain areas, with the highest concentrations in the occipital cortex, regardless of the diet. Zeaxanthin was present in all brain regions but only in the BF infants; it was present in both retinal regions in all groups but was significantly enhanced in BF infants compared to either formula group (P lutein concentrations compared to unsupplemented formula, concentrations were still well below those in BF infants. Regardless of diet, occipital cortex showed selectively higher lutein deposition than other brain regions, suggesting lutein's role in visual processing in early life. © 2018 American Society for Nutrition. All rights reserved.

  13. Regional cholinesterase activity in white-throated sparrow brain is differentially affected by acephate (Orthene®)

    Science.gov (United States)

    Vyas, N.B.; Kuenzel, W.J.; Hill, E.F.; Romo, G.A.; Komaragiri, M.V.S.

    1996-01-01

    Effects of a 14-day dietary exposure to an organophosphorus pesticide, acephate (acetylphosphoramidothioic acid O,S-dimethyl ester), were determined on cholinesterase activity in three regions (basal ganglia, hippocampus, and hypothalamus) of the white-throated sparrow, Zonotrichia albicollis, brain. All three regions experienced depressed cholinesterase activity between 0.5–2 ppm acephate. The regions exhibited cholinesterase recovery at 2–16 ppm acephate; however, cholinesterase activity dropped and showed no recovery at higher dietary levels (>16 ppm acephate). Evidence indicates that the recovery is initiated by the magnitude of depression, not the duration. In general, as acephate concentration increased, differences in ChE activity among brain regions decreased. Three terms are introduced to describe ChE response to acephate exposure: 1) ChE resistance threshold, 2) ChE compensation threshold, and 3) ChE depression threshold. It is hypothesized that adverse effects to birds in the field may occur at pesticide exposure levels customarily considered negligible.

  14. Bilingualism alters brain functional connectivity between "control" regions and "language" regions: Evidence from bimodal bilinguals.

    Science.gov (United States)

    Li, Le; Abutalebi, Jubin; Zou, Lijuan; Yan, Xin; Liu, Lanfang; Feng, Xiaoxia; Wang, Ruiming; Guo, Taomei; Ding, Guosheng

    2015-05-01

    Previous neuroimaging studies have revealed that bilingualism induces both structural and functional neuroplasticity in the dorsal anterior cingulate cortex (dACC) and the left caudate nucleus (LCN), both of which are associated with cognitive control. Since these "control" regions should work together with other language regions during language processing, we hypothesized that bilingualism may also alter the functional interaction between the dACC/LCN and language regions. Here we tested this hypothesis by exploring the functional connectivity (FC) in bimodal bilinguals and monolinguals using functional MRI when they either performed a picture naming task with spoken language or were in resting state. We found that for bimodal bilinguals who use spoken and sign languages, the FC of the dACC with regions involved in spoken language (e.g. the left superior temporal gyrus) was stronger in performing the task, but weaker in the resting state as compared to monolinguals. For the LCN, its intrinsic FC with sign language regions including the left inferior temporo-occipital part and right inferior and superior parietal lobules was increased in the bilinguals. These results demonstrate that bilingual experience may alter the brain functional interaction between "control" regions and "language" regions. For different control regions, the FC alters in different ways. The findings also deepen our understanding of the functional roles of the dACC and LCN in language processing. Copyright © 2015 Elsevier Ltd. All rights reserved.

  15. Molecular basis of immunogenicity to botulinum neurotoxins and uses of the defined antigenic regions.

    Science.gov (United States)

    Atassi, M Z

    2015-12-01

    Intensive research in this laboratory over the last 19 years has aimed at understanding the molecular bases for immune recognition of botulinum neurotoxin, types A and B and the role of anti-toxin immune responses in defense against the toxin. Using 92 synthetic 19-residue peptides that overlapped by 5 residues and comprised an entire toxin (A or B) we determined the peptides' ability to bind anti-toxin Abs of human, mouse, horse and chicken. We also localized the epitopes recognized by Abs of cervical dystonia patients who developed immunoresistance to correlate toxin during treatment with BoNT/A or BoNT/B. For BoNT/A, patients' blocking Abs bound to 13 regions (5 on L and 8 on H subunit) on the surface and the response to each region was under separate MHC control. The responses were defined by the structure of the antigen and by the MHC of the host. The antigenic regions coincided or overlapped with synaptosomes (SNPS) binding regions. Antibody binding blocked the toxin's ability to bind to neuronal cells. In fact selected synthetic peptides were able to inhibit the toxin's action in vivo. A combination of three synthetic strong antigenic peptides detected blocking Abs in 88% of immunoresistant patients' sera. Administration of selected epitopes, pre-linked at their N(α) group to monomethoxyployethylene glycol, into mice with ongoing blocking anti-toxin Abs, reduced blocking Ab levels in the recipients. This may be suitable for clinical applications. Defined epitopes should also be valuable in synthetic vaccines design. Copyright © 2015 Elsevier Ltd. All rights reserved.

  16. Age-and Brain Region-Specific Differences in Mitochondrial Bioenergetics in Brown Norway Rats

    Science.gov (United States)

    Mitochondria are central regulators of energy homeostasis and play a pivotal role in mechanisms of cellular senescence. The objective of the present study was to evaluate mitochondrial bio­-energetic parameters in five brain regions [brainstem (BS), frontal cortex (FC), cerebellu...

  17. Associations between regional brain volumes at term-equivalent age and development at 2 years of age in preterm children

    International Nuclear Information System (INIS)

    Lind, Annika; Parkkola, Riitta; Lehtonen, Liisa; Maunu, Jonna; Lapinleimu, Helena; Munck, Petriina; Haataja, Leena

    2011-01-01

    Altered brain volumes and associations between volumes and developmental outcomes have been reported in prematurely born children. To assess which regional brain volumes are different in very low birth weight (VLBW) children without neurodevelopmental impairments ([NDI] cerebral palsy, hearing loss, blindness and significantly delayed cognitive performance) compared with VLBW children with NDI, and to evaluate the association between regional brain volumes at term-equivalent age and cognitive development and neurological performance at a corrected age of 2 years. The study group consisted of a regional cohort of 164 VLBW children, divided into one group of children without NDI (n = 148) and one group of children with NDI (n = 16). Brain (MRI) was performed at term-equivalent age, from which brain volumes were manually analysed. Cognitive development was assessed with the Bayley Scales of Infant Development II (BSID-II), and neurological performance with the Hammersmith Infant Neurological Examination at the corrected age of 2 years. The volumes of total brain tissue, cerebrum, frontal lobes, basal ganglia and thalami, and cerebellum were significantly smaller, and the volume of the ventricles significantly larger, in the children with NDI than in those without NDI. Even in children without NDI, a smaller cerebellar volume was significantly correlated with poor neurological performance at 2 years of corrected age. Volumetric analysis at brain MRI can provide an additional parameter for early prediction of outcome in VLBW children. (orig.)

  18. Associations between regional brain volumes at term-equivalent age and development at 2 years of age in preterm children

    Energy Technology Data Exchange (ETDEWEB)

    Lind, Annika [Turku University Hospital, Department of Pediatrics, Turku (Finland); Aabo Akademi University, Department of Psychology, Turku (Finland); Parkkola, Riitta [University of Turku and Turku University Hospital, Department of Radiology and Turku PET Center, PO Box 52, Turku (Finland); Lehtonen, Liisa; Maunu, Jonna; Lapinleimu, Helena [University of Turku and Turku University Hospital, Department of Pediatrics, Turku (Finland); Munck, Petriina [Turku University Hospital, Department of Pediatrics, Turku (Finland); University of Turku, Department of Psychology, Turku (Finland); Haataja, Leena [University of Turku and Turku University Hospital, Department of Pediatric Neurology, Turku (Finland)

    2011-08-15

    Altered brain volumes and associations between volumes and developmental outcomes have been reported in prematurely born children. To assess which regional brain volumes are different in very low birth weight (VLBW) children without neurodevelopmental impairments ([NDI] cerebral palsy, hearing loss, blindness and significantly delayed cognitive performance) compared with VLBW children with NDI, and to evaluate the association between regional brain volumes at term-equivalent age and cognitive development and neurological performance at a corrected age of 2 years. The study group consisted of a regional cohort of 164 VLBW children, divided into one group of children without NDI (n = 148) and one group of children with NDI (n = 16). Brain (MRI) was performed at term-equivalent age, from which brain volumes were manually analysed. Cognitive development was assessed with the Bayley Scales of Infant Development II (BSID-II), and neurological performance with the Hammersmith Infant Neurological Examination at the corrected age of 2 years. The volumes of total brain tissue, cerebrum, frontal lobes, basal ganglia and thalami, and cerebellum were significantly smaller, and the volume of the ventricles significantly larger, in the children with NDI than in those without NDI. Even in children without NDI, a smaller cerebellar volume was significantly correlated with poor neurological performance at 2 years of corrected age. Volumetric analysis at brain MRI can provide an additional parameter for early prediction of outcome in VLBW children. (orig.)

  19. Cannabis cue-induced brain activation correlates with drug craving in limbic and visual salience regions: Preliminary results

    Science.gov (United States)

    Charboneau, Evonne J.; Dietrich, Mary S.; Park, Sohee; Cao, Aize; Watkins, Tristan J; Blackford, Jennifer U; Benningfield, Margaret M.; Martin, Peter R.; Buchowski, Maciej S.; Cowan, Ronald L.

    2013-01-01

    Craving is a major motivator underlying drug use and relapse but the neural correlates of cannabis craving are not well understood. This study sought to determine whether visual cannabis cues increase cannabis craving and whether cue-induced craving is associated with regional brain activation in cannabis-dependent individuals. Cannabis craving was assessed in 16 cannabis-dependent adult volunteers while they viewed cannabis cues during a functional MRI (fMRI) scan. The Marijuana Craving Questionnaire was administered immediately before and after each of three cannabis cue-exposure fMRI runs. FMRI blood-oxygenation-level-dependent (BOLD) signal intensity was determined in regions activated by cannabis cues to examine the relationship of regional brain activation to cannabis craving. Craving scores increased significantly following exposure to visual cannabis cues. Visual cues activated multiple brain regions, including inferior orbital frontal cortex, posterior cingulate gyrus, parahippocampal gyrus, hippocampus, amygdala, superior temporal pole, and occipital cortex. Craving scores at baseline and at the end of all three runs were significantly correlated with brain activation during the first fMRI run only, in the limbic system (including amygdala and hippocampus) and paralimbic system (superior temporal pole), and visual regions (occipital cortex). Cannabis cues increased craving in cannabis-dependent individuals and this increase was associated with activation in the limbic, paralimbic, and visual systems during the first fMRI run, but not subsequent fMRI runs. These results suggest that these regions may mediate visually cued aspects of drug craving. This study provides preliminary evidence for the neural basis of cue-induced cannabis craving and suggests possible neural targets for interventions targeted at treating cannabis dependence. PMID:24035535

  20. An edge-centric perspective on the human connectome: link communities in the brain.

    Science.gov (United States)

    de Reus, Marcel A; Saenger, Victor M; Kahn, René S; van den Heuvel, Martijn P

    2014-10-05

    Brain function depends on efficient processing and integration of information within a complex network of neural interactions, known as the connectome. An important aspect of connectome architecture is the existence of community structure, providing an anatomical basis for the occurrence of functional specialization. Typically, communities are defined as groups of densely connected network nodes, representing clusters of brain regions. Looking at the connectome from a different perspective, instead focusing on the interconnecting links or edges, we find that the white matter pathways between brain regions also exhibit community structure. Eleven link communities were identified: five spanning through the midline fissure, three through the left hemisphere and three through the right hemisphere. We show that these link communities are consistently identifiable and investigate the network characteristics of their underlying white matter pathways. Furthermore, examination of the relationship between link communities and brain regions revealed that the majority of brain regions participate in multiple link communities. In particular, the highly connected and central hub regions showed a rich level of community participation, supporting the notion that these hubs play a pivotal role as confluence zones in which neural information from different domains merges. © 2014 The Author(s) Published by the Royal Society. All rights reserved.

  1. Regional differences in the expression of brain-derived neurotrophic factor (BDNF) pro-peptide, proBDNF and preproBDNF in the brain confer stress resilience.

    Science.gov (United States)

    Yang, Bangkun; Yang, Chun; Ren, Qian; Zhang, Ji-Chun; Chen, Qian-Xue; Shirayama, Yukihiko; Hashimoto, Kenji

    2016-12-01

    Using learned helplessness (LH) model of depression, we measured protein expression of brain-derived neurotrophic factor (BDNF) pro-peptide, BDNF precursors (proBDNF and preproBDNF) in the brain regions of LH (susceptible) and non-LH rats (resilience). Expression of preproBDNF, proBDNF and BDNF pro-peptide in the medial prefrontal cortex of LH rats, but not non-LH rats, was significantly higher than control rats, although expression of these proteins in the nucleus accumbens of LH rats was significantly lower than control rats. This study suggests that regional differences in conversion of BDNF precursors into BDNF and BDNF pro-peptide by proteolytic cleavage may contribute to stress resilience.

  2. Identification of alterations associated with age in the clustering structure of functional brain networks.

    Science.gov (United States)

    Guzman, Grover E C; Sato, Joao R; Vidal, Maciel C; Fujita, Andre

    2018-01-01

    Initial studies using resting-state functional magnetic resonance imaging on the trajectories of the brain network from childhood to adulthood found evidence of functional integration and segregation over time. The comprehension of how healthy individuals' functional integration and segregation occur is crucial to enhance our understanding of possible deviations that may lead to brain disorders. Recent approaches have focused on the framework wherein the functional brain network is organized into spatially distributed modules that have been associated with specific cognitive functions. Here, we tested the hypothesis that the clustering structure of brain networks evolves during development. To address this hypothesis, we defined a measure of how well a brain region is clustered (network fitness index), and developed a method to evaluate its association with age. Then, we applied this method to a functional magnetic resonance imaging data set composed of 397 males under 31 years of age collected as part of the Autism Brain Imaging Data Exchange Consortium. As results, we identified two brain regions for which the clustering change over time, namely, the left middle temporal gyrus and the left putamen. Since the network fitness index is associated with both integration and segregation, our finding suggests that the identified brain region plays a role in the development of brain systems.

  3. Parametrically defined cerebral blood vessels as non-invasive blood input functions for brain PET studies

    International Nuclear Information System (INIS)

    Asselin, Marie-Claude; Cunningham, Vincent J; Amano, Shigeko; Gunn, Roger N; Nahmias, Claude

    2004-01-01

    A non-invasive alternative to arterial blood sampling for the generation of a blood input function for brain positron emission tomography (PET) studies is presented. The method aims to extract the dimensions of the blood vessel directly from PET images and to simultaneously correct the radioactivity concentration for partial volume and spillover. This involves simulation of the tomographic imaging process to generate images of different blood vessel and background geometries and selecting the one that best fits, in a least-squares sense, the acquired PET image. A phantom experiment was conducted to validate the method which was then applied to eight subjects injected with 6-[ 18 F]fluoro-L-DOPA and one subject injected with [ 11 C]CO-labelled red blood cells. In the phantom study, the diameter of syringes filled with an 11 C solution and inserted into a water-filled cylinder were estimated with an accuracy of half a pixel (1 mm). The radioactivity concentration was recovered to 100 ± 4% in the 8.7 mm diameter syringe, the one that most closely approximated the superior sagittal sinus. In the human studies, the method systematically overestimated the calibre of the superior sagittal sinus by 2-3 mm compared to measurements made in magnetic resonance venograms on the same subjects. Sources of discrepancies related to the anatomy of the blood vessel were found not to be fundamental limitations to the applicability of the method to human subjects. This method has the potential to provide accurate quantification of blood radioactivity concentration from PET images without the need for blood samples, corrections for delay and dispersion, co-registered anatomical images, or manually defined regions of interest

  4. Surface regions of illusory images are detected with a slower processing speed than those of luminance-defined images.

    Science.gov (United States)

    Mihaylova, Milena; Manahilov, Velitchko

    2010-11-24

    Research has shown that the processing time for discriminating illusory contours is longer than for real contours. We know, however, little whether the visual processes, associated with detecting regions of illusory surfaces, are also slower as those responsible for detecting luminance-defined images. Using a speed-accuracy trade-off (SAT) procedure, we measured accuracy as a function of processing time for detecting illusory Kanizsa-type and luminance-defined squares embedded in 2D static luminance noise. The data revealed that the illusory images were detected at slower processing speed than the real images, while the points in time, when accuracy departed from chance, were not significantly different for both stimuli. The classification images for detecting illusory and real squares showed that observers employed similar detection strategies using surface regions of the real and illusory squares. The lack of significant differences between the x-intercepts of the SAT functions for illusory and luminance-modulated stimuli suggests that the detection of surface regions of both images could be based on activation of a single mechanism (the dorsal magnocellular visual pathway). The slower speed for detecting illusory images as compared to luminance-defined images could be attributed to slower processes of filling-in of regions of illusory images within the dorsal pathway.

  5. Quantitative evaluation of regional cerebral blood flow by visual stimulation in 99mTc-HMPAO brain SPECT

    International Nuclear Information System (INIS)

    Juh, R. H.; Suh, T. S.; Chung, Y. A.

    2002-01-01

    The purpose of this study is to investigate the effects of visual activation and quantitative analysis of regional cerebral blood flow. Visual activation was known to increase regional cerebral blood flow in the visual cortex in occipital lobe. We evaluated that change in the distribution of 99mTc-HMPAO (Hexamethyl propylene amine oxime) to reflect in regional cerebral blood flow. The six volunteers were injected with 925 MBq (mean ages: 26.75 years, n=6, 3men, 3women) underwent MRI and 99mTc- HMPAO SPECT during a rest state with closed eyes and visual stimulated with 8 Hz LED. We delineate the region of interest and calculated the mean count per voxel in each of the fifteen slices to quantitative analysis. The ROI to whole brain ratio and regional index was calculated pixel to pixel subtraction visual non-activation image from visual activation image and constructed brain map using a statistical parameter map (SPM99). The mean regional cerebral blood flow was increased due to visual stimulation. The increase rate of the mean regional cerebral blood flow which of the activation region in primary visual cortex of occipital lobe was 32.50±5.67%. The significant activation sites using a statistical parameter of brain constructed a rendering image and image fusion with SPECT and MRI. Visual activation was revealed significant increase through quantitative analysis in visual cortex. Activation region was certified in Talairach coordinate and primary visual cortex (Ba17),visual association area (Ba18,19) of Brodmann

  6. Quantitative evaluation of regional cerebral blood flow by visual stimulation in 99mTc- HMPAO brain SPECT

    International Nuclear Information System (INIS)

    Juh, Ra Hyeong; Suh, Tae Suk; Kwark, Chul Eun; Choe, Bo Young; Lee, Hyoung Koo; Chung, Yong An; Kim, Sung Hoon; Chung, Soo Kyo

    2002-01-01

    The purpose of this study is to investigate the effects of visual activation and quantitative analysis of regional cerebral blood flow. Visual activation was known to increase regional cerebral blood flow in the visual cortex in occipital lobe. We evaluated that change in the distribution of '9 9m Tc-HMPAO (Hexamethyl propylene amine oxime) to reflect in regional cerebral blood flow. The six volunteers were injected with 925 MBq (mean ages: 26.75 years, n=6, 3men, 3women) underwent MRI and 99m Tc-HMPAO SPECT during a rest state with closed eyes and visual stimulated with 8 Hz LED. We delineate the region of interest and calculated the mean count per voxel in each of the fifteen slices to quantitative analysis. The ROI to whole brain ratio and regional index was calculated pixel to pixel subtraction visual non-activation image from visual activation image and constructed brain map using a statistical parameter map(SPM99). The mean regional cerebral blood flow was increased due to visual stimulation. The increase rate of the mean regional cerebral blood flow which of the activation region in primary visual cortex of occipital lobe was 32.50±5.67%. The significant activation sites using a statistical parameter of brain constructed a rendering image and image fusion with SPECT and MRI. Visual activation was revealed significant increase through quantitative analysis in visual cortex. Activation region was certified in Talairach coordinate and primary visual cortex (Ba17),visual association area (Ba18,19) of Brodmann

  7. Social defeat promotes a reactive endothelium in a brain region-dependent manner with increased expression of key adhesion molecules, selectins and chemokines associated with the recruitment of myeloid cells to the brain.

    Science.gov (United States)

    Sawicki, C M; McKim, D B; Wohleb, E S; Jarrett, B L; Reader, B F; Norden, D M; Godbout, J P; Sheridan, J F

    2015-08-27

    Repeated social defeat (RSD) in mice causes myeloid cell trafficking to the brain that contributes to the development of prolonged anxiety-like behavior. Myeloid cell recruitment following RSD occurs in regions where neuronal and microglia activation is observed. Thus, we hypothesized that crosstalk between neurons, microglia, and endothelial cells contributes to brain myeloid cell trafficking via chemokine signaling and vascular adhesion molecules. Here we show that social defeat caused an exposure- and brain region-dependent increase in several key adhesion molecules and chemokines involved in the recruitment of myeloid cells. For example, RSD induced distinct patterns of adhesion molecule expression that may explain brain region-dependent myeloid cell trafficking. VCAM-1 and ICAM-1 mRNA expression were increased in an exposure-dependent manner. Furthermore, RSD-induced VCAM-1 and ICAM-1 protein expression were localized to the vasculature of brain regions implicated in fear and anxiety responses, which spatially corresponded to previously reported patterns of myeloid cell trafficking. Next, mRNA expression of additional adhesion molecules (E- and P-selectin, PECAM-1) and chemokines (CXCL1, CXCL2, CXCL12, CCL2) were determined in the brain. Social defeat induced an exposure-dependent increase in mRNA levels of E-selectin, CXCL1, and CXCL2 that increased with additional days of social defeat. While CXCL12 was unaffected by RSD, CCL2 expression was increased by six days of social defeat. Last, comparison between enriched CD11b(+) cells (microglia/macrophages) and enriched GLAST-1(+)/CD11b(-) cells (astrocytes) revealed RSD increased mRNA expression of IL-1β, CCL2, and CXCL2 in microglia/macrophages but not in astrocytes. Collectively, these data indicate that key mediators of leukocyte recruitment were increased in the brain vasculature following RSD in an exposure- and brain region-dependent manner. Copyright © 2014 IBRO. Published by Elsevier Ltd. All rights

  8. Intrinsic brain networks normalize with treatment in pediatric complex regional pain syndrome

    Science.gov (United States)

    Becerra, Lino; Sava, Simona; Simons, Laura E.; Drosos, Athena M.; Sethna, Navil; Berde, Charles; Lebel, Alyssa A.; Borsook, David

    2014-01-01

    Pediatric complex regional pain syndrome (P-CRPS) offers a unique model of chronic neuropathic pain as it either resolves spontaneously or through therapeutic interventions in most patients. Here we evaluated brain changes in well-characterized children and adolescents with P-CRPS by measuring resting state networks before and following a brief (median = 3 weeks) but intensive physical and psychological treatment program, and compared them to matched healthy controls. Differences in intrinsic brain networks were observed in P-CRPS compared to controls before treatment (disease state) with the most prominent differences in the fronto-parietal, salience, default mode, central executive, and sensorimotor networks. Following treatment, behavioral measures demonstrated a reduction of symptoms and improvement of physical state (pain levels and motor functioning). Correlation of network connectivities with spontaneous pain measures pre- and post-treatment indicated concomitant reductions in connectivity in salience, central executive, default mode and sensorimotor networks (treatment effects). These results suggest a rapid alteration in global brain networks with treatment and provide a venue to assess brain changes in CRPS pre- and post-treatment, and to evaluate therapeutic effects. PMID:25379449

  9. Intrinsic brain networks normalize with treatment in pediatric complex regional pain syndrome

    Directory of Open Access Journals (Sweden)

    Lino Becerra

    2014-01-01

    Full Text Available Pediatric complex regional pain syndrome (P-CRPS offers a unique model of chronic neuropathic pain as it either resolves spontaneously or through therapeutic interventions in most patients. Here we evaluated brain changes in well-characterized children and adolescents with P-CRPS by measuring resting state networks before and following a brief (median = 3 weeks but intensive physical and psychological treatment program, and compared them to matched healthy controls. Differences in intrinsic brain networks were observed in P-CRPS compared to controls before treatment (disease state with the most prominent differences in the fronto-parietal, salience, default mode, central executive, and sensorimotor networks. Following treatment, behavioral measures demonstrated a reduction of symptoms and improvement of physical state (pain levels and motor functioning. Correlation of network connectivities with spontaneous pain measures pre- and post-treatment indicated concomitant reductions in connectivity in salience, central executive, default mode and sensorimotor networks (treatment effects. These results suggest a rapid alteration in global brain networks with treatment and provide a venue to assess brain changes in CRPS pre- and post-treatment, and to evaluate therapeutic effects.

  10. Regional brain activity during early visual perception in unaffected siblings of schizophrenia patients.

    Science.gov (United States)

    Lee, Junghee; Cohen, Mark S; Engel, Stephen A; Glahn, David; Nuechterlein, Keith H; Wynn, Jonathan K; Green, Michael F

    2010-07-01

    Visual masking paradigms assess the early part of visual information processing, which may reflect vulnerability measures for schizophrenia. We examined the neural substrates of visual backward performance in unaffected sibling of schizophrenia patients using functional magnetic resonance imaging (fMRI). Twenty-one unaffected siblings of schizophrenia patients and 19 healthy controls performed a backward masking task and three functional localizer tasks to identify three visual processing regions of interest (ROI): lateral occipital complex (LO), the motion-sensitive area, and retinotopic areas. In the masking task, we systematically manipulated stimulus onset asynchronies (SOAs). We analyzed fMRI data in two complementary ways: 1) an ROI approach for three visual areas, and 2) a whole-brain analysis. The groups did not differ in behavioral performance. For ROI analysis, both groups increased activation as SOAs increased in LO. Groups did not differ in activation levels of the three ROIs. For whole-brain analysis, controls increased activation as a function of SOAs, compared with siblings in several regions (i.e., anterior cingulate cortex, posterior cingulate cortex, inferior prefrontal cortex, inferior parietal lobule). The study found: 1) area LO showed sensitivity to the masking effect in both groups; 2) siblings did not differ from controls in activation of LO; and 3) groups differed significantly in several brain regions outside visual processing areas that have been related to attentional or re-entrant processes. These findings suggest that LO dysfunction may be a disease indicator rather than a risk indicator for schizophrenia. Copyright 2010 Society of Biological Psychiatry. Published by Elsevier Inc. All rights reserved.

  11. Regional brain changes occurring during disobedience to "experts" in financial decision-making.

    Directory of Open Access Journals (Sweden)

    Victoria Y M Suen

    Full Text Available It is well recognized that individuals follow "Expert" advice, even when flawed and offers no advantage, and sometimes leads to disadvantages. The neurobiology underlying this is uncertain, and in particular there is an incomplete understanding of which brain regions are most involved when individuals chose to disobey an expert. To study this we examined functional magnetic resonance imaging (fMRI differences during an investment game where subjects received differentially credible investment advice. Participants (n = 42; 32 males played an investment game, in which they could Buy or Not Buy a sequence of stocks. The better they did, the more money they made. Participants received either "Expert" advice or "Peer" advice. Those receiving Expert advice were told the advice came from a certified financial "Expert". Those receiving Peer Advice were told the advice was that of the student administering the scans, who deliberately dressed and acted casually. Both streams of advice were predetermined and identical. The advice was scripted to be helpful initially, but progressively worse as the task continued, becoming 100% wrong by the end of the task. Subjects receiving Expert Advice followed the advice significantly longer on average, even though this was progressively worse advice. Thus, following Expert advice had poorer consequences for individuals, but this did not dissuade them from continuing to follow the advice. In contrast, when subjects disobeyed Expert advice they exhibited significant anterior cingulate cortex (ACC and superior frontal gyrus activation relative to those disobeying Peer advice. These findings may suggest that in subjects who defy authority, or believe they are doing so (in this case by disobeying an "Expert" there is increased activation of these two brain regions. This may have relevance to several areas of behavior, and the potential role of these two brain regions in regard to disobedience behavior requires further

  12. Regional volumes and spatial volumetric distribution of gray matter in the gender dysphoric brain.

    OpenAIRE

    Hoekzema, Elseline; Schagen, Sebastian E. E.; Kreukels, Baudewijntje P. C.; Veltman, Dick J.; Cohen-Kettenis, Peggy T.; Delemarre-van de Waal, Henriette; Bakker, Julie

    2015-01-01

    The sexual differentiation of the brain is primarily driven by gonadal hormones during fetal development. Leading theories on the etiology of gender dysphoria (GD) involve deviations herein. To examine whether there are signs of a sex-atypical brain development in GD, we quantified regional neural gray matter (GM) volumes in 55 female-to-male and 38 male-to-female adolescents, 44 boys and 52 girls without GD and applied both univariate and multivariate analyses. In girls, more GM volume was o...

  13. Hypothyroidism coordinately and transiently affects myelin protein gene expression in most rat brain regions during postnatal development.

    Science.gov (United States)

    Ibarrola, N; Rodríguez-Peña, A

    1997-03-28

    To assess the role of thyroid hormone on myelin gene expression, we have studied the effect of hypothyroidism on the mRNA steady state levels for the major myelin protein genes: myelin basic protein (MBP), proteolipid protein (PLP), myelin-associated glycoprotein (MAG) and 2':3'-cyclic nucleotide 3'-phosphodiesterase (CNP) in different rat brain regions, during the first postnatal month. We found that hypothyroidism reduces the levels of every myelin protein transcript, with striking differences between the different brain regions. Thus, in the more caudal regions, the effect of hypothyroidism was extremely modest, being only evident at the earlier stages of myelination. In contrast, in the striatum and the cerebral cortex the important decrease in the myelin protein transcripts is maintained beyond the first postnatal month. Therefore, thyroid hormone modulates in a synchronous fashion the expression of the myelin genes and the length of its effect depends on the brain region. On the other hand, hyperthyroidism leads to an increase of the major myelin protein transcripts above control values. Finally, lack of thyroid hormone does not change the expression of the oligodendrocyte progenitor-specific gene, the platelet derived growth factor receptor alpha.

  14. Associations between regional brain volumes at term-equivalent age and development at 2 years of age in preterm children.

    Science.gov (United States)

    Lind, Annika; Parkkola, Riitta; Lehtonen, Liisa; Munck, Petriina; Maunu, Jonna; Lapinleimu, Helena; Haataja, Leena

    2011-08-01

    Altered brain volumes and associations between volumes and developmental outcomes have been reported in prematurely born children. To assess which regional brain volumes are different in very low birth weight (VLBW) children without neurodevelopmental impairments ([NDI] cerebral palsy, hearing loss, blindness and significantly delayed cognitive performance) compared with VLBW children with NDI, and to evaluate the association between regional brain volumes at term-equivalent age and cognitive development and neurological performance at a corrected age of 2 years. The study group consisted of a regional cohort of 164 VLBW children, divided into one group of children without NDI (n = 148) and one group of children with NDI (n = 16). Brain (MRI) was performed at term-equivalent age, from which brain volumes were manually analysed. Cognitive development was assessed with the Bayley Scales of Infant Development II (BSID-II), and neurological performance with the Hammersmith Infant Neurological Examination at the corrected age of 2 years. The volumes of total brain tissue, cerebrum, frontal lobes, basal ganglia and thalami, and cerebellum were significantly smaller, and the volume of the ventricles significantly larger, in the children with NDI than in those without NDI. Even in children without NDI, a smaller cerebellar volume was significantly correlated with poor neurological performance at 2 years of corrected age. Volumetric analysis at brain MRI can provide an additional parameter for early prediction of outcome in VLBW children.

  15. Pseudotyped Lentiviral Vectors for Retrograde Gene Delivery into Target Brain Regions

    Directory of Open Access Journals (Sweden)

    Kenta Kobayashi

    2017-08-01

    Full Text Available Gene transfer through retrograde axonal transport of viral vectors offers a substantial advantage for analyzing roles of specific neuronal pathways or cell types forming complex neural networks. This genetic approach may also be useful in gene therapy trials by enabling delivery of transgenes into a target brain region distant from the injection site of the vectors. Pseudotyping of a lentiviral vector based on human immunodeficiency virus type 1 (HIV-1 with various fusion envelope glycoproteins composed of different combinations of rabies virus glycoprotein (RV-G and vesicular stomatitis virus glycoprotein (VSV-G enhances the efficiency of retrograde gene transfer in both rodent and nonhuman primate brains. The most recently developed lentiviral vector is a pseudotype with fusion glycoprotein type E (FuG-E, which demonstrates highly efficient retrograde gene transfer in the brain. The FuG-E–pseudotyped vector permits powerful experimental strategies for more precisely investigating the mechanisms underlying various brain functions. It also contributes to the development of new gene therapy approaches for neurodegenerative disorders, such as Parkinson’s disease, by delivering genes required for survival and protection into specific neuronal populations. In this review article, we report the properties of the FuG-E–pseudotyped vector, and we describe the application of the vector to neural circuit analysis and the potential use of the FuG-E vector in gene therapy for Parkinson’s disease.

  16. Activation of Erk and JNK MAPK pathways by acute swim stress in rat brain regions

    Directory of Open Access Journals (Sweden)

    Salvadore Christopher

    2004-09-01

    Full Text Available Abstract Background The mitogen-activated protein kinases (MAPKs have been shown to participate in a wide array of cellular functions. A role for some MAPKs (e.g., extracellular signal-regulated kinase, Erk1/2 has been documented in response to certain physiological stimuli, such as ischemia, visceral pain and electroconvulsive shock. We recently demonstrated that restraint stress activates the Erk MAPK pathway, but not c-Jun-N-terminal kinase/stress-activated protein kinase (JNK/SAPK or p38MAPK, in several rat brain regions. In the present study, we investigated the effects of a different stressor, acute forced swim stress, on the phosphorylation (P state of these MAPKs in the hippocampus, neocortex, prefrontal cortex, amygdala and striatum. In addition, effects on the phosphorylation state of the upstream activators of the MAPKs, their respective MAPK kinases (MAPKKs; P-MEK1/2, P-MKK4 and P-MKK3/6, were determined. Finally, because the Erk pathway can activate c-AMP response element (CRE binding (CREB protein, and swim stress has recently been reported to enhance CREB phosphorylation, changes in P-CREB were also examined. Results A single 15 min session of forced swimming increased P-Erk2 levels 2–3-fold in the neocortex, prefrontal cortex and striatum, but not in the hippocampus or amygdala. P-JNK levels (P-JNK1 and/or P-JNK2/3 were increased in all brain regions about 2–5-fold, whereas P-p38MAPK levels remained essentially unchanged. Surprisingly, levels of the phosphorylated MAPKKs, P-MEK1/2 and P-MKK4 (activators of the Erk and JNK pathways, respectively were increased in all five brain regions, and much more dramatically (P-MEK1/2, 4.5 to > 100-fold; P-MKK4, 12 to ~300-fold. Consistent with the lack of forced swim on phosphorylation of p38MAPK, there appeared to be no change in levels of its activator, P-MKK3/6. P-CREB was increased in all but cortical (prefrontal, neocortex areas. Conclusions Swim stress specifically and markedly

  17. Localisation of the brain in fetal MRI using bundled SIFT features.

    Science.gov (United States)

    Keraudren, Kevin; Kyriakopoulou, Vanessa; Rutherford, Mary; Hajnal, Joseph V; Rueckert, Daniel

    2013-01-01

    Fetal MRI is a rapidly emerging diagnostic imaging tool. Its main focus is currently on brain imaging, but there is a huge potential for whole body studies. We propose a method for accurate and robust localisation of the fetal brain in MRI when the image data is acquired as a stack of 2D slices misaligned due to fetal motion. We first detect possible brain locations in 2D images with a Bag-of-Words model using SIFT features aggregated within Maximally Stable Extremal Regions (called bundled SIFT), followed by a robust fitting of an axis-aligned 3D box to the selected regions. We rely on prior knowledge of the fetal brain development to define size and shape constraints. In a cross-validation experiment, we obtained a median error distance of 5.7mm from the ground truth and no missed detection on a database of 59 fetuses. This 2D approach thus allows a robust detection even in the presence of substantial fetal motion.

  18. Effects of traumatic brain injury on regional cerebral blood flow in rats as measured with radiolabeled microspheres

    International Nuclear Information System (INIS)

    Yamakami, I.; McIntosh, T.K.

    1989-01-01

    To clarify the effect of experimental brain injury on regional CBF (rCBF), repeated rCBF measurements were performed using radiolabeled microspheres in rats subjected to fluid-percussion traumatic brain injury. Three consecutive microsphere injections in six uninjured control rats substantiated that the procedure induces no significant changes in hemodynamic variables or rCBF. Animals were subjected to left parietal fluid-percussion brain injury of moderate severity (2.1-2.4 atm) and rCBF values were determined (a) prior to injury and 15 min and 1 h following injury (n = 7); and (b) prior to injury and 30 min and 2 h following injury (n = 7). At 15 min post injury, there was a profound reduction of rCBF in all brain regions studied (p less than 0.01). Although rCBF in the hindbrain had recovered to near-normal by 30 min post injury, rCBF in both injured and contralateral (uninjured) forebrain areas remained significantly suppressed up to 1 h post injury. At 2 h post injury, recovery of rCBF to near-normal values was observed in all brain regions except the focal area of injury (left parietal cortex) where rCBF remained significantly depressed (p less than 0.01). This prolonged focal oligemia at the injury site was associated with the development of reproducible cystic necrosis in the left parietotemporal cortex at 4 weeks post injury. Our results demonstrate that acute changes in rCBF occur following experimental traumatic brain injury in rats and that rCBF remains significantly depressed up to 2 h post injury in the area circumscribing the trauma site

  19. Aberrant brain regional homogeneity and functional connectivity in middle-aged T2DM patients: a resting-state functional MRI study

    Directory of Open Access Journals (Sweden)

    Daihong Liu

    2016-09-01

    Full Text Available Type 2 diabetes mellitus (T2DM has been associated with cognitive impairment. However, its neurological mechanism remains elusive. Combining regional homogeneity (ReHo and functional connectivity (FC analyses, the present study aimed to investigate brain functional alterations in middle-aged T2DM patients, which could provide complementary information for the neural substrates underlying T2DM-associated brain dysfunction. Twenty-five T2DM patients and 25 healthy controls were involved in neuropsychological testing and structural and resting-state functional magnetic resonance imaging data acquisition. ReHo analysis was conducted to determine the peak coordinates of brain regions with abnormal local brain activity synchronization. Then, the identified brain regions were considered as seeds, and FC between these brain regions and global voxels was computed. Finally, the potential correlations between the imaging indices and neuropsychological data were also explored. Compared with healthy controls, T2DM patients exhibited higher ReHo values in the anterior cingulate gyrus and lower ReHo in right fusiform gyrus, right precentral gyrus and right medial orbit of the superior frontal gyrus. Considering these areas as seed regions, T2DM patients displayed aberrant FC, mainly in the frontal and parietal lobes. The pattern of FC alterations in T2DM patients was characterized by decreased connectivity and positive to negative or negative to positive converted connectivity. Digital Span Test forward scores revealed significant correlations with the ReHo values of the right precentral gyrus (ρ = 0.527, p = 0.014 and FC between the right fusiform gyrus and middle temporal gyrus (ρ = -0.437, p = 0.048. Our findings suggest that T2DM patients suffer from cognitive dysfunction related to spatially local and remote brain activity synchronization impairment. The patterns of ReHo and FC alterations shed light on the mechanisms underlying T2DM-associated brain

  20. Differential effects of ethanol on regional glutamatergic and GABAergic neurotransmitter pathways in mouse brain.

    Science.gov (United States)

    Tiwari, Vivek; Veeraiah, Pandichelvam; Subramaniam, Vaidyanathan; Patel, Anant Bahadur

    2014-03-01

    This study investigates the effects of ethanol on neuronal and astroglial metabolism using (1)H-[(13)C]-NMR spectroscopy in conjunction with infusion of [1,6-(13)C2]/[1-(13)C]glucose or [2-(13)C]acetate, respectively. A three-compartment metabolic model was fitted to the (13)C turnover of GluC3 , GluC4, GABAC 2, GABAC 3, AspC3 , and GlnC4 from [1,6-(13)C2 ]glucose to determine the rates of tricarboxylic acid (TCA) and neurotransmitter cycle associated with glutamatergic and GABAergic neurons. The ratio of neurotransmitter cycle to TCA cycle fluxes for glutamatergic and GABAegic neurons was obtained from the steady-state [2-(13)C]acetate experiment and used as constraints during the metabolic model fitting. (1)H MRS measurement suggests that depletion of ethanol from cerebral cortex follows zero order kinetics with rate 0.18 ± 0.04 μmol/g/min. Acute exposure of ethanol reduces the level of glutamate and aspartate in cortical region. GlnC4 labeling was found to be unchanged from a 15 min infusion of [2-(13)C]acetate suggesting that acute ethanol exposure does not affect astroglial metabolism in naive mice. Rates of TCA and neurotransmitter cycle associated with glutamatergic and GABAergic neurons were found to be significantly reduced in cortical and subcortical regions. Acute exposure of ethanol perturbs the level of neurometabolites and decreases the excitatory and inhibitory activity differentially across the regions of brain. Depletion of ethanol and its effect on brain functions were measured using (1)H and (1)H-[(13)C]-NMR spectroscopy in conjunction with infusion of (13)C-labeled substrates. Ethanol depletion from brain follows zero order kinetics. Ethanol perturbs level of glutamate, and the excitatory and inhibitory activity in mice brain. © 2013 International Society for Neurochemistry.

  1. Regional volumes and spatial volumetric distribution of gray matter in the gender dysphoric brain.

    Science.gov (United States)

    Hoekzema, Elseline; Schagen, Sebastian E E; Kreukels, Baudewijntje P C; Veltman, Dick J; Cohen-Kettenis, Peggy T; Delemarre-van de Waal, Henriette; Bakker, Julie

    2015-05-01

    The sexual differentiation of the brain is primarily driven by gonadal hormones during fetal development. Leading theories on the etiology of gender dysphoria (GD) involve deviations herein. To examine whether there are signs of a sex-atypical brain development in GD, we quantified regional neural gray matter (GM) volumes in 55 female-to-male and 38 male-to-female adolescents, 44 boys and 52 girls without GD and applied both univariate and multivariate analyses. In girls, more GM volume was observed in the left superior medial frontal cortex, while boys had more volume in the bilateral superior posterior hemispheres of the cerebellum and the hypothalamus. Regarding the GD groups, at whole-brain level they differed only from individuals sharing their gender identity but not from their natal sex. Accordingly, using multivariate pattern recognition analyses, the GD groups could more accurately be automatically discriminated from individuals sharing their gender identity than those sharing their natal sex based on spatially distributed GM patterns. However, region of interest analyses indicated less GM volume in the right cerebellum and more volume in the medial frontal cortex in female-to-males in comparison to girls without GD, while male-to-females had less volume in the bilateral cerebellum and hypothalamus than natal boys. Deviations from the natal sex within sexually dimorphic structures were also observed in the untreated subsamples. Our findings thus indicate that GM distribution and regional volumes in GD adolescents are largely in accordance with their respective natal sex. However, there are subtle deviations from the natal sex in sexually dimorphic structures, which can represent signs of a partial sex-atypical differentiation of the brain. Copyright © 2015 Elsevier Ltd. All rights reserved.

  2. Mercury distribution and speciation in different brain regions of beluga whales (Delphinapterus leucas)

    Energy Technology Data Exchange (ETDEWEB)

    Ostertag, Sonja K., E-mail: ostertag@unbc.ca [Natural Resources and Environmental Studies, University of Northern British Columbia, Prince George, British Columbia, V2N 4Z9 (Canada); Stern, Gary A., E-mail: Gary.Stern@dfo-mpo.gc.ca [Freshwater Institute, Fisheries and Oceans Canada, Winnipeg, Manitoba, R3T 2N6 (Canada); Centre for Earth Observation Science, Department of Environment and Geography, University of Manitoba, Winnipeg, Manitoba, R3T 2N2 (Canada); Wang, Feiyue, E-mail: feiyue.wang@ad.umanitoba.ca [Centre for Earth Observation Science, Department of Environment and Geography, University of Manitoba, Winnipeg, Manitoba, R3T 2N2 (Canada); Department of Chemistry, University of Manitoba, Winnipeg, Manitoba, R3T 2N2 (Canada); Lemes, Marcos, E-mail: Marcos.lemes@ad.umanitoba.ca [Centre for Earth Observation Science, Department of Environment and Geography, University of Manitoba, Winnipeg, Manitoba, R3T 2N2 (Canada); Chan, Hing Man, E-mail: laurie.chan@uottawa.ca [Center for Advanced Research in Environmental Genomics, University of Ottawa, Ottawa, Ontario, 1N 6N5 (Canada)

    2013-07-01

    The toxicokinetics of mercury (Hg) in key species of Arctic ecosystem are poorly understood. We sampled five brain regions (frontal lobe, temporal lobe, cerebellum, brain stem and spinal cord) from beluga whales (Delphinapterus leucas) harvested in 2006, 2008, and 2010 from the eastern Beaufort Sea, Canada, and measured total Hg (HgT) and total selenium (SeT) by inductively coupled plasma mass spectrometry (ICP-MS), mercury analyzer or cold vapor atomic absorption spectrometry, and the chemical forms using a high performance liquid chromatography ICP-MS. At least 14% of the beluga whales had HgT concentrations higher than the levels of observable adverse effect (6.0 mg kg{sup −1} wet weight (ww)) in primates. The concentrations of HgT differed between brain regions; median concentrations (mg kg{sup −1} ww) were 2.34 (0.06 to 22.6, 81) (range, n) in temporal lobe, 1.84 (0.12 to 21.9, 77) in frontal lobe, 1.84 (0.05 to 16.9, 83) in cerebellum, 1.25 (0.02 to 11.1, 77) in spinal cord and 1.32 (0.13 to 15.2, 39) in brain stem. Total Hg concentrations in the cerebellum increased with age (p < 0.05). Between 35 and 45% of HgT was water-soluble, of which, 32 to 41% was methyl mercury (MeHg) and 59 to 68% was labile inorganic Hg. The concentration of MeHg (range: 0.03 to 1.05 mg kg{sup −1} ww) was positively associated with HgT concentration, and the percent MeHg (4 to 109%) decreased exponentially with increasing HgT concentration in the spinal cord, cerebellum, frontal lobe and temporal lobe. There was a positive association between SeT and HgT in all brain regions (p < 0.05) suggesting that Se may play a role in the detoxification of Hg in the brain. The concentration of HgT in the cerebellum was significantly associated with HgT in other organs. Therefore, HgT concentrations in organs that are frequently sampled in bio-monitoring studies could be used to estimate HgT concentrations in the cerebellum, which is the target organ of MeHg toxicity. - Highlights:

  3. Brain regional {alpha}-[{sup 11}C]methyl-L-tryptophan trapping, used as an index of 5-HT synthesis, in healthy adults: absence of an age effect

    Energy Technology Data Exchange (ETDEWEB)

    Rosa-Neto, Pedro; Benkelfat, Chawki; Leyton, Marco [Department of Neurology and Neurosurgery, Montreal (Canada); McGill University, Department of Psychiatry, Montreal, Quebec (Canada); Sakai, Yojiro [Department of Neurology and Neurosurgery, Montreal (Canada); University of Tokyo, Department of Psychosomatic Medicine, Tokyo (Japan); Morais, Jose A. [McGill University, Department of Geriatrics, Montreal, Quebec (Canada); Diksic, Mirko [Department of Neurology and Neurosurgery, Montreal (Canada)

    2007-08-15

    Previous functional neuroimaging studies suggest that selective aspects of the brain serotonin (5-HT) system change during the aging process. Here, we assessed the effects of aging on the brain regional {alpha}-[{sup 11}C]methyl-L-tryptophan ({alpha}-[{sup 11}C]MTrp) trapping rate constant (K*; {mu}l.g{sup -1}.min{sup -1}), which, with certain assumptions, could be taken as a proxy of 5-HT synthesis. Thirty-six healthy right-handed subjects had positron emission tomography (PET) scans following injection with {alpha}-[{sup 11}C]MTrp [18 males aged 46.6 {+-} 22.2 years (range 20-80 years) and 18 females aged 33.0 {+-} 15.5 years (range 20-80 years)]. The trapping rate constant, K*, was calculated with the graphical method for irreversible ligands using the sinus-venous input function. A priori selected volumes of interest (VOIs) were defined using an automatic algorithm. VOI analysis showed no correlation between age and brain regional K* values. As reported by others, significant age-related reductions of gray matter were observed in the thalamus and frontal and cingulate cortices; even with partial volume correction there was still no significant relationship between K* and age. Further exploratory SPM voxelwise correlation between age and {alpha}-[{sup 11}C]MTrp trapping, using p = 0.05 (uncorrected), as well as voxel-based morphometry, was in agreement with the VOI analysis. The dissociation between age-related changes in brain anatomy and this index of serotonin synthesis suggests independent mechanisms underlying the normal aging process. (orig.)

  4. Development of an MRI rating scale for multiple brain regions: comparison with volumetrics and with voxel-based morphometry

    International Nuclear Information System (INIS)

    Davies, R.R.; Williams, Guy B.; Scahill, Victoria L.; Graham, Kim S.; Graham, Andrew; Hodges, John R.

    2009-01-01

    We aimed to devise a rating method for key frontal and temporal brain regions validated against quantitative volumetric methods and applicable to a range of dementia syndromes. Four standardised coronal MR images from 36 subjects encompassing controls and cases with Alzheimer's disease (AD) and frontotemporal dementia (FTD) were used. After initial pilot studies, 15 regions produced good intra- and inter-rater reliability. We then validated the ratings against manual volumetry and voxel-based morphometry (VBM) and compared ratings across the subject groups. Validation against both manual volumetry (for both frontal and temporal lobes), and against whole brain VBM, showed good correlation with visual ratings for the majority of the brain regions. Comparison of rating scores across disease groups showed involvement of the anterior fusiform gyrus, anterior hippocampus and temporal pole in semantic dementia, while anterior cingulate and orbitofrontal regions were involved in behavioural variant FTD. This simple visual rating can be used as an alternative to highly technical methods of quantification, and may be superior when dealing with single cases or small groups. (orig.)

  5. Development of an MRI rating scale for multiple brain regions: comparison with volumetrics and with voxel-based morphometry

    Energy Technology Data Exchange (ETDEWEB)

    Davies, R.R.; Williams, Guy B. [University of Cambridge, Department of Clinical Neurosciences, Cambridge (United Kingdom); Scahill, Victoria L.; Graham, Kim S. [Cardiff University, MRC Cognition and Brain Sciences Unit, Cambridge and Wales Institute of Cognitive Neuroscience, School of Psychology, Cardiff (United Kingdom); Graham, Andrew [University of Cambridge, Department of Clinical Neurosciences, Cambridge (United Kingdom); Cardiff University, MRC Cognition and Brain Sciences Unit, Cambridge and Wales Institute of Cognitive Neuroscience, School of Psychology, Cardiff (United Kingdom); Hodges, John R. [University of Cambridge, Department of Clinical Neurosciences, Cambridge (United Kingdom); Cardiff University, MRC Cognition and Brain Sciences Unit, Cambridge and Wales Institute of Cognitive Neuroscience, School of Psychology, Cardiff (United Kingdom); Prince of Wales Medical Research Institute, Cognitive Neurology, Sydney, NSW (Australia)

    2009-08-15

    We aimed to devise a rating method for key frontal and temporal brain regions validated against quantitative volumetric methods and applicable to a range of dementia syndromes. Four standardised coronal MR images from 36 subjects encompassing controls and cases with Alzheimer's disease (AD) and frontotemporal dementia (FTD) were used. After initial pilot studies, 15 regions produced good intra- and inter-rater reliability. We then validated the ratings against manual volumetry and voxel-based morphometry (VBM) and compared ratings across the subject groups. Validation against both manual volumetry (for both frontal and temporal lobes), and against whole brain VBM, showed good correlation with visual ratings for the majority of the brain regions. Comparison of rating scores across disease groups showed involvement of the anterior fusiform gyrus, anterior hippocampus and temporal pole in semantic dementia, while anterior cingulate and orbitofrontal regions were involved in behavioural variant FTD. This simple visual rating can be used as an alternative to highly technical methods of quantification, and may be superior when dealing with single cases or small groups. (orig.)

  6. Probing the brain with molecular fMRI.

    Science.gov (United States)

    Ghosh, Souparno; Harvey, Peter; Simon, Jacob C; Jasanoff, Alan

    2018-04-09

    One of the greatest challenges of modern neuroscience is to incorporate our growing knowledge of molecular and cellular-scale physiology into integrated, organismic-scale models of brain function in behavior and cognition. Molecular-level functional magnetic resonance imaging (molecular fMRI) is a new technology that can help bridge these scales by mapping defined microscopic phenomena over large, optically inaccessible regions of the living brain. In this review, we explain how MRI-detectable imaging probes can be used to sensitize noninvasive imaging to mechanistically significant components of neural processing. We discuss how a combination of innovative probe design, advanced imaging methods, and strategies for brain delivery can make molecular fMRI an increasingly successful approach for spatiotemporally resolved studies of diverse neural phenomena, perhaps eventually in people. Copyright © 2018 Elsevier Ltd. All rights reserved.

  7. Functional specificity for high-level linguistic processing in the human brain.

    Science.gov (United States)

    Fedorenko, Evelina; Behr, Michael K; Kanwisher, Nancy

    2011-09-27

    Neuroscientists have debated for centuries whether some regions of the human brain are selectively engaged in specific high-level mental functions or whether, instead, cognition is implemented in multifunctional brain regions. For the critical case of language, conflicting answers arise from the neuropsychological literature, which features striking dissociations between deficits in linguistic and nonlinguistic abilities, vs. the neuroimaging literature, which has argued for overlap between activations for linguistic and nonlinguistic processes, including arithmetic, domain general abilities like cognitive control, and music. Here, we use functional MRI to define classic language regions functionally in each subject individually and then examine the response of these regions to the nonlinguistic functions most commonly argued to engage these regions: arithmetic, working memory, cognitive control, and music. We find little or no response in language regions to these nonlinguistic functions. These data support a clear distinction between language and other cognitive processes, resolving the prior conflict between the neuropsychological and neuroimaging literatures.

  8. Complex Regional Pain Syndrome Type I Affects Brain Structure in Prefrontal and Motor Cortex

    Science.gov (United States)

    Pleger, Burkhard; Draganski, Bogdan; Schwenkreis, Peter; Lenz, Melanie; Nicolas, Volkmar; Maier, Christoph; Tegenthoff, Martin

    2014-01-01

    The complex regional pain syndrome (CRPS) is a rare but debilitating pain disorder that mostly occurs after injuries to the upper limb. A number of studies indicated altered brain function in CRPS, whereas possible influences on brain structure remain poorly investigated. We acquired structural magnetic resonance imaging data from CRPS type I patients and applied voxel-by-voxel statistics to compare white and gray matter brain segments of CRPS patients with matched controls. Patients and controls were statistically compared in two different ways: First, we applied a 2-sample ttest to compare whole brain white and gray matter structure between patients and controls. Second, we aimed to assess structural alterations specifically of the primary somatosensory (S1) and motor cortex (M1) contralateral to the CRPS affected side. To this end, MRI scans of patients with left-sided CRPS (and matched controls) were horizontally flipped before preprocessing and region-of-interest-based group comparison. The unpaired ttest of the “non-flipped” data revealed that CRPS patients presented increased gray matter density in the dorsomedial prefrontal cortex. The same test applied to the “flipped” data showed further increases in gray matter density, not in the S1, but in the M1 contralateral to the CRPS-affected limb which were inversely related to decreased white matter density of the internal capsule within the ipsilateral brain hemisphere. The gray-white matter interaction between motor cortex and internal capsule suggests compensatory mechanisms within the central motor system possibly due to motor dysfunction. Altered gray matter structure in dorsomedial prefrontal cortex may occur in response to emotional processes such as pain-related suffering or elevated analgesic top-down control. PMID:24416397

  9. Complex regional pain syndrome type I affects brain structure in prefrontal and motor cortex.

    Directory of Open Access Journals (Sweden)

    Burkhard Pleger

    Full Text Available The complex regional pain syndrome (CRPS is a rare but debilitating pain disorder that mostly occurs after injuries to the upper limb. A number of studies indicated altered brain function in CRPS, whereas possible influences on brain structure remain poorly investigated. We acquired structural magnetic resonance imaging data from CRPS type I patients and applied voxel-by-voxel statistics to compare white and gray matter brain segments of CRPS patients with matched controls. Patients and controls were statistically compared in two different ways: First, we applied a 2-sample ttest to compare whole brain white and gray matter structure between patients and controls. Second, we aimed to assess structural alterations specifically of the primary somatosensory (S1 and motor cortex (M1 contralateral to the CRPS affected side. To this end, MRI scans of patients with left-sided CRPS (and matched controls were horizontally flipped before preprocessing and region-of-interest-based group comparison. The unpaired ttest of the "non-flipped" data revealed that CRPS patients presented increased gray matter density in the dorsomedial prefrontal cortex. The same test applied to the "flipped" data showed further increases in gray matter density, not in the S1, but in the M1 contralateral to the CRPS-affected limb which were inversely related to decreased white matter density of the internal capsule within the ipsilateral brain hemisphere. The gray-white matter interaction between motor cortex and internal capsule suggests compensatory mechanisms within the central motor system possibly due to motor dysfunction. Altered gray matter structure in dorsomedial prefrontal cortex may occur in response to emotional processes such as pain-related suffering or elevated analgesic top-down control.

  10. Workshops of the Fifth International Brain-Computer Interface Meeting: Defining the Future.

    Science.gov (United States)

    Huggins, Jane E; Guger, Christoph; Allison, Brendan; Anderson, Charles W; Batista, Aaron; Brouwer, Anne-Marie A-M; Brunner, Clemens; Chavarriaga, Ricardo; Fried-Oken, Melanie; Gunduz, Aysegul; Gupta, Disha; Kübler, Andrea; Leeb, Robert; Lotte, Fabien; Miller, Lee E; Müller-Putz, Gernot; Rutkowski, Tomasz; Tangermann, Michael; Thompson, David Edward

    2014-01-01

    The Fifth International Brain-Computer Interface (BCI) Meeting met June 3-7 th , 2013 at the Asilomar Conference Grounds, Pacific Grove, California. The conference included 19 workshops covering topics in brain-computer interface and brain-machine interface research. Topics included translation of BCIs into clinical use, standardization and certification, types of brain activity to use for BCI, recording methods, the effects of plasticity, special interest topics in BCIs applications, and future BCI directions. BCI research is well established and transitioning to practical use to benefit people with physical impairments. At the same time, new applications are being explored, both for people with physical impairments and beyond. Here we provide summaries of each workshop, illustrating the breadth and depth of BCI research and high-lighting important issues for future research and development.

  11. Effect of prolonged exposure to diesel engine exhaust on proinflammatory markers in different regions of the rat brain.

    Science.gov (United States)

    Gerlofs-Nijland, Miriam E; van Berlo, Damien; Cassee, Flemming R; Schins, Roel P F; Wang, Kate; Campbell, Arezoo

    2010-05-17

    The etiology and progression of neurodegenerative disorders depends on the interactions between a variety of factors including: aging, environmental exposures, and genetic susceptibility factors. Enhancement of proinflammatory events appears to be a common link in different neurological impairments, including Alzheimer's disease, Parkinson's disease, amyotrophic lateral sclerosis, and multiple sclerosis. Studies have shown a link between exposure to particulate matter (PM), present in air pollution, and enhancement of central nervous system proinflammatory markers. In the present study, the association between exposure to air pollution (AP), derived from a specific source (diesel engine), and neuroinflammation was investigated. To elucidate whether specific regions of the brain are more susceptible to exposure to diesel-derived AP, various loci of the brain were separately analyzed. Rats were exposed for 6 hrs a day, 5 days a week, for 4 weeks to diesel engine exhaust (DEE) using a nose-only exposure chamber. The day after the final exposure, the brain was dissected into the following regions: cerebellum, frontal cortex, hippocampus, olfactory bulb and tubercles, and the striatum. Baseline levels of the pro-inflammatory cytokines tumor necrosis factor alpha (TNF-alpha) and interleukin-1 alpha (IL-1alpha) were dependent on the region analyzed and increased in the striatum after exposure to DEE. In addition, baseline level of activation of the transcription factors (NF-kappaB) and (AP-1) was also region dependent but the levels were not significantly altered after exposure to DEE. A similar, though not significant, trend was seen with the mRNA expression levels of TNF-alpha and TNF Receptor-subtype I (TNF-RI). Our results indicate that different brain regions may be uniquely responsive to changes induced by exposure to DEE. This study once more underscores the role of neuroinflammation in response to ambient air pollution, however, it is valuable to assess if and to

  12. Effect of prolonged exposure to diesel engine exhaust on proinflammatory markers in different regions of the rat brain

    Directory of Open Access Journals (Sweden)

    Wang Kate

    2010-05-01

    Full Text Available Abstract Background The etiology and progression of neurodegenerative disorders depends on the interactions between a variety of factors including: aging, environmental exposures, and genetic susceptibility factors. Enhancement of proinflammatory events appears to be a common link in different neurological impairments, including Alzheimer's disease, Parkinson's disease, amyotrophic lateral sclerosis, and multiple sclerosis. Studies have shown a link between exposure to particulate matter (PM, present in air pollution, and enhancement of central nervous system proinflammatory markers. In the present study, the association between exposure to air pollution (AP, derived from a specific source (diesel engine, and neuroinflammation was investigated. To elucidate whether specific regions of the brain are more susceptible to exposure to diesel-derived AP, various loci of the brain were separately analyzed. Rats were exposed for 6 hrs a day, 5 days a week, for 4 weeks to diesel engine exhaust (DEE using a nose-only exposure chamber. The day after the final exposure, the brain was dissected into the following regions: cerebellum, frontal cortex, hippocampus, olfactory bulb and tubercles, and the striatum. Results Baseline levels of the pro-inflammatory cytokines tumor necrosis factor alpha (TNF-α and interleukin-1 alpha (IL-1α were dependent on the region analyzed and increased in the striatum after exposure to DEE. In addition, baseline level of activation of the transcription factors (NF-κB and (AP-1 was also region dependent but the levels were not significantly altered after exposure to DEE. A similar, though not significant, trend was seen with the mRNA expression levels of TNF-α and TNF Receptor-subtype I (TNF-RI. Conclusions Our results indicate that different brain regions may be uniquely responsive to changes induced by exposure to DEE. This study once more underscores the role of neuroinflammation in response to ambient air pollution

  13. Regional Differences in Brain Volume Predict the Acquisition of Skill in a Complex Real-Time Strategy Videogame

    Science.gov (United States)

    Basak, Chandramallika; Voss, Michelle W.; Erickson, Kirk I.; Boot, Walter R.; Kramer, Arthur F.

    2011-01-01

    Previous studies have found that differences in brain volume among older adults predict performance in laboratory tasks of executive control, memory, and motor learning. In the present study we asked whether regional differences in brain volume as assessed by the application of a voxel-based morphometry technique on high resolution MRI would also…

  14. Training of verbal creativity modulates brain activity in regions associated with language‐ and memory‐related demands

    Science.gov (United States)

    Benedek, Mathias; Koschutnig, Karl; Pirker, Eva; Berger, Elisabeth; Meister, Sabrina; Neubauer, Aljoscha C.; Papousek, Ilona; Weiss, Elisabeth M.

    2015-01-01

    Abstract This functional magnetic resonance (fMRI) study was designed to investigate changes in functional patterns of brain activity during creative ideation as a result of a computerized, 3‐week verbal creativity training. The training was composed of various verbal divergent thinking exercises requiring participants to train approximately 20 min per day. Fifty‐three participants were tested three times (psychometric tests and fMRI assessment) with an intertest‐interval of 4 weeks each. Participants were randomly assigned to two different training groups, which received the training time‐delayed: The first training group was trained between the first and the second test, while the second group accomplished the training between the second and the third test session. At the behavioral level, only one training group showed improvements in different facets of verbal creativity right after the training. Yet, functional patterns of brain activity during creative ideation were strikingly similar across both training groups. Whole‐brain voxel‐wise analyses (along with supplementary region of interest analyses) revealed that the training was associated with activity changes in well‐known creativity‐related brain regions such as the left inferior parietal cortex and the left middle temporal gyrus, which have been shown as being particularly sensitive to the originality facet of creativity in previous research. Taken together, this study demonstrates that continuous engagement in a specific complex cognitive task like divergent thinking is associated with reliable changes of activity patterns in relevant brain areas, suggesting more effective search, retrieval, and integration from internal memory representations as a result of the training. Hum Brain Mapp 36:4104–4115, 2015. © 2015 The Authors Human Brain Mapping Published by Wiley Periodicals, Inc. PMID:26178653

  15. Proteomic analysis of proteins expressing in regions of rat brain by a combination of SDS-PAGE with nano-liquid chromatography-quadrupole-time of flight tandem mass spectrometry

    Directory of Open Access Journals (Sweden)

    Maekawa Tsuyoshi

    2010-07-01

    Full Text Available Abstract Background Most biological functions controlled by the brain and their related disorders are closely associated with activation in specific regions of the brain. Neuroproteomics has been applied to the analysis of whole brain, and the general pattern of protein expression in all regions has been elucidated. However, the comprehensive proteome of each brain region remains unclear. Results In this study, we carried out comparative proteomics of six regions of the adult rat brain: thalamus, hippocampus, frontal cortex, parietal cortex, occipital cortex, and amygdala using semi-quantitative analysis by Mascot Score of the identified proteins. In order to identify efficiently the proteins that are present in the brain, the proteins were separated by a combination of SDS-PAGE on a C18 column-equipped nano-liquid chromatograph, and analyzed by quadrupole-time of flight-tandem-mass spectrometry. The proteomic data show 2,909 peptides in the rat brain, with more than 200 identified as region-abundant proteins by semi-quantitative analysis. The regions containing the identified proteins are membrane (20.0%, cytoplasm (19.5%, mitochondrion (17.1%, cytoskeleton (8.2%, nucleus (4.7%, extracellular region (3.3%, and other (18.0%. Of the identified proteins, the expressions of glial fibrillary acidic protein, GABA transporter 3, Septin 5, heat shock protein 90, synaptotagmin, heat shock protein 70, and pyruvate kinase were confirmed by immunoblotting. We examined the distributions in rat brain of GABA transporter 3, glial fibrillary acidic protein, and heat shock protein 70 by immunohistochemistry, and found that the proteins are localized around the regions observed by proteomic analysis and immunoblotting. IPA analysis indicates that pathways closely related to the biological functions of each region may be activated in rat brain. Conclusions These observations indicate that proteomics in each region of adult rat brain may provide a novel way to

  16. Cis-regulatory elements in the primate brain: from functional specialization to neurodegeneration

    NARCIS (Netherlands)

    Vermunt, Marit W.

    2017-01-01

    Over the last decade, the noncoding part of the genome has been shown to harbour thousands of cis-regulatory elements, such as enhancers, that activate well-defined gene expression programs. Here, we charted active enhancers in a multiplicity of human brain regions to understand the role of

  17. Quantitative evaluation of regional cerebral blood flow by visual stimulation in {sup 99m}Tc- HMPAO brain SPECT

    Energy Technology Data Exchange (ETDEWEB)

    Juh, Ra Hyeong; Suh, Tae Suk; Kwark, Chul Eun; Choe, Bo Young; Lee, Hyoung Koo; Chung, Yong An; Kim, Sung Hoon; Chung, Soo Kyo [College of Medicine, The Catholic Univ. of Seoul, Seoul (Korea, Republic of)

    2002-06-01

    The purpose of this study is to investigate the effects of visual activation and quantitative analysis of regional cerebral blood flow. Visual activation was known to increase regional cerebral blood flow in the visual cortex in occipital lobe. We evaluated that change in the distribution of '9{sup 9m}Tc-HMPAO (Hexamethyl propylene amine oxime) to reflect in regional cerebral blood flow. The six volunteers were injected with 925 MBq (mean ages: 26.75 years, n=6, 3men, 3women) underwent MRI and {sup 99m}Tc-HMPAO SPECT during a rest state with closed eyes and visual stimulated with 8 Hz LED. We delineate the region of interest and calculated the mean count per voxel in each of the fifteen slices to quantitative analysis. The ROI to whole brain ratio and regional index was calculated pixel to pixel subtraction visual non-activation image from visual activation image and constructed brain map using a statistical parameter map(SPM99). The mean regional cerebral blood flow was increased due to visual stimulation. The increase rate of the mean regional cerebral blood flow which of the activation region in primary visual cortex of occipital lobe was 32.50{+-}5.67%. The significant activation sites using a statistical parameter of brain constructed a rendering image and image fusion with SPECT and MRI. Visual activation was revealed significant increase through quantitative analysis in visual cortex. Activation region was certified in Talairach coordinate and primary visual cortex (Ba17),visual association area (Ba18,19) of Brodmann.

  18. Quantitative evaluation of regional cerebral blood flow by visual stimulation in {sup 99m}Tc-HMPAO brain SPECT

    Energy Technology Data Exchange (ETDEWEB)

    Juh, R. H.; Suh, T. S.; Chung, Y. A. [The Catholic Univ., of Korea, Seoul (Korea, Republic of)

    2002-07-01

    The purpose of this study is to investigate the effects of visual activation and quantitative analysis of regional cerebral blood flow. Visual activation was known to increase regional cerebral blood flow in the visual cortex in occipital lobe. We evaluated that change in the distribution of 99mTc-HMPAO (Hexamethyl propylene amine oxime) to reflect in regional cerebral blood flow. The six volunteers were injected with 925 MBq (mean ages: 26.75 years, n=6, 3men, 3women) underwent MRI and 99mTc- HMPAO SPECT during a rest state with closed eyes and visual stimulated with 8 Hz LED. We delineate the region of interest and calculated the mean count per voxel in each of the fifteen slices to quantitative analysis. The ROI to whole brain ratio and regional index was calculated pixel to pixel subtraction visual non-activation image from visual activation image and constructed brain map using a statistical parameter map (SPM99). The mean regional cerebral blood flow was increased due to visual stimulation. The increase rate of the mean regional cerebral blood flow which of the activation region in primary visual cortex of occipital lobe was 32.50{+-}5.67%. The significant activation sites using a statistical parameter of brain constructed a rendering image and image fusion with SPECT and MRI. Visual activation was revealed significant increase through quantitative analysis in visual cortex. Activation region was certified in Talairach coordinate and primary visual cortex (Ba17),visual association area (Ba18,19) of Brodmann.

  19. Reversible and regionally selective downregulation of brain cannabinoid CB1 receptors in chronic daily cannabis smokers

    OpenAIRE

    Hirvonen, J; Goodwin, RS; Li, C-T; Terry, GE; Zoghbi, SS; Morse, C; Pike, VW; Volkow, ND; Huestis, MA; Innis, RB

    2011-01-01

    Chronic cannabis (marijuana, hashish) smoking can result in dependence. Rodent studies show reversible downregulation of brain cannabinoid CB1 (cannabinoid receptor type 1) receptors after chronic exposure to cannabis. However, whether downregulation occurs in humans who chronically smoke cannabis is unknown. Here we show, using positron emission tomography imaging, reversible and regionally selective downregulation of brain cannabinoid CB1 receptors in human subjects who chronically smoke ca...

  20. Functional connections between activated and deactivated brain regions mediate emotional interference during externally directed cognition.

    Science.gov (United States)

    Di Plinio, Simone; Ferri, Francesca; Marzetti, Laura; Romani, Gian Luca; Northoff, Georg; Pizzella, Vittorio

    2018-04-24

    Recent evidence shows that task-deactivations are functionally relevant for cognitive performance. Indeed, higher cognitive engagement has been associated with higher suppression of activity in task-deactivated brain regions - usually ascribed to the Default Mode Network (DMN). Moreover, a negative correlation between these regions and areas actively engaged by the task is associated with better performance. DMN regions show positive modulation during autobiographical, social, and emotional tasks. However, it is not clear how processing of emotional stimuli affects the interplay between the DMN and executive brain regions. We studied this interplay in an fMRI experiment using emotional negative stimuli as distractors. Activity modulations induced by the emotional interference of negative stimuli were found in frontal, parietal, and visual areas, and were associated with modulations of functional connectivity between these task-activated areas and DMN regions. A worse performance was predicted both by lower activity in the superior parietal cortex and higher connectivity between visual areas and frontal DMN regions. Connectivity between right inferior frontal gyrus and several DMN regions in the left hemisphere was related to the behavioral performance. This relation was weaker in the negative than in the neutral condition, likely suggesting less functional inhibitions of DMN regions during emotional processing. These results show that both executive and DMN regions are crucial for the emotional interference process and suggest that DMN connections are related to the interplay between externally-directed and internally-focused processes. Among DMN regions, superior frontal gyrus may be a key node in regulating the interference triggered by emotional stimuli. © 2018 Wiley Periodicals, Inc.

  1. Preliminary application of voxel-based morphometry technique on brain changes in neuromyelitis

    International Nuclear Information System (INIS)

    Xiao Hui; Ma Lin; Chen Ziqian; Lou Xin; Chen Zhiye

    2011-01-01

    Objective: To investigate the changes of brain volumes in neuromyelitis optica (NMO) patients using voxel-based morphometry (VBM) method, and preliminarily explore the pattern of cerebral anatomical impairment. Methods: Twenty-three clinically defined NMO patients and 15 gender and age matched healthy volunteers underwent 3-dimensional (3D) fast spoiled gradient echo (FSPGR) sequence scanning on 3.0 Tesla MR system. Raw data was processed and analyzed using statistical parametric mapping (SPM) 5. Whole brain volumes included grey matter volume (GMV), white matter volume (WMV), total intracranial volume (TIV), grey matter fraction (GMF), white matter fraction (WMF), brain tissue fraction (BTF) and regional brain volumes between the two groups were compared by independent samples t-test and an Pearson were performed to compare the regional brain volumes and the ages. Results: GMV of NMO group [(610.2±55.0) ml] was significantly decreased comparing to healthy control group [(657.2±36.3) ml] (t=-2.915, P<0.05). The age of NMO patients [(40±9) years old] showed negative correlation with GMF [(42.5±2.6) %] (r=-0.673, P<0.05). Regional brain volume analysis showed decreased GMV in left insula and bilateral posterior cingutates in NMO patients, while decreased WMV was found in left frontal and left parietal white matter. Conclusion: VBM could detect brain volume changes sensitively. Total grey matter volume in NMO patients was decreased comparing to HC group. Regional grey matter atrophy in NMO patients occurred in left insular and bilateral posterior cingutates, regional white matter atrophy occurred in left frontal and left parietal lobe. (authors)

  2. Workbench surface editor of brain cortical surface

    Science.gov (United States)

    Dow, Douglas E.; Nowinski, Wieslaw L.; Serra, Luis

    1996-04-01

    We have developed a 3D reach-in tool to manually reconstruct 3D cortical surface patches from 2D brain atlas images. The first application of our cortex editor is building 3D functional maps, specifically Brodmann's areas. This tool may also be useful in clinical practice to adjust incorrectly mapped atlas regions due to the deforming effect of lesions. The cortex editor allows a domain expert to control the correlation of control points across slices. Correct correlation has been difficult for 3D reconstruction algorithms because the atlas slices are far apart and because of the complex topology of the cortex which differs so much from slice to slice. Also, higher precision of the resulting surfaces is demanded since these define 3D brain atlas features upon which future stereotactic surgery may be based. The cortex editor described in this paper provides a tool suitable for a domain expert to use in defining the 3D surface of a Brodmann's area.

  3. Air pollutant sulfur dioxide-induced alterations on the levels of lipids, lipid peroxidation and lipase activity in various regions of the rat brain

    Energy Technology Data Exchange (ETDEWEB)

    Haider, S S; Hasan, M; Khan, N H

    1982-07-01

    The exposure of rats to SO/sub 2/ (10 p.p.m.) for one hour daily for 30 days caused depletion of total lipids in all brain areas. The contents of phospholipid were elevated in cerebellum and brain stem, but were depleted in cerebral hemisphere. Cholesterol levels showed an increase in various brain regions. On the other hand, gangliosides were increased in cerebellum and brain stem, but were decreased in cerebral hemisphere. Interestingly, cholesterol/phospholipid ratio was increased in different regions of the brain. Lipase activity was elevated in cerebral hemisphere. Lipid peroxidation showed marked increment in whole brain and in all the brain areas studied. The results suggest that SO/sub 2/-exposure induces degradation of lipids. Interestingly, the lipid contents are affected differentially in the various parts of the brain.

  4. Cortical Thinning in Network-Associated Regions in Cognitively Normal and Below-Normal Range Schizophrenia

    Directory of Open Access Journals (Sweden)

    R. Walter Heinrichs

    2017-01-01

    Full Text Available This study assessed whether cortical thickness across the brain and regionally in terms of the default mode, salience, and central executive networks differentiates schizophrenia patients and healthy controls with normal range or below-normal range cognitive performance. Cognitive normality was defined using the MATRICS Consensus Cognitive Battery (MCCB composite score (T=50 ± 10 and structural magnetic resonance imaging was used to generate cortical thickness data. Whole brain analysis revealed that cognitively normal range controls (n=39 had greater cortical thickness than both cognitively normal (n=17 and below-normal range (n=49 patients. Cognitively normal controls also demonstrated greater thickness than patients in regions associated with the default mode and salience, but not central executive networks. No differences on any thickness measure were found between cognitively normal range and below-normal range controls (n=24 or between cognitively normal and below-normal range patients. In addition, structural covariance between network regions was high and similar across subgroups. Positive and negative symptom severity did not correlate with thickness values. Cortical thinning across the brain and regionally in relation to the default and salience networks may index shared aspects of the psychotic psychopathology that defines schizophrenia with no relation to cognitive impairment.

  5. Novel transcripts discovered by mining genomic DNA from defined regions of bovine chromosome 6

    Directory of Open Access Journals (Sweden)

    Eberlein Annett

    2009-04-01

    Full Text Available Abstract Background Linkage analyses strongly suggest a number of QTL for production, health and conformation traits in the middle part of bovine chromosome 6 (BTA6. The identification of the molecular background underlying the genetic variation at the QTL and subsequent functional studies require a well-annotated gene sequence map of the critical QTL intervals. To complete the sequence map of the defined subchromosomal regions on BTA6 poorly covered with comparative gene information, we focused on targeted isolation of transcribed sequences from bovine bacterial artificial chromosome (BAC clones mapped to the QTL intervals. Results Using the method of exon trapping, 92 unique exon trapping sequences (ETS were discovered in a chromosomal region of poor gene coverage. Sequence identity to the current NCBI sequence assembly for BTA6 was detected for 91% of unique ETS. Comparative sequence similarity search revealed that 11% of the isolated ETS displayed high similarity to genomic sequences located on the syntenic chromosomes of the human and mouse reference genome assemblies. Nearly a third of the ETS identified similar equivalent sequences in genomic sequence scaffolds from the alternative Celera-based sequence assembly of the human genome. Screening gene, EST, and protein databases detected 17% of ETS with identity to known transcribed sequences. Expression analysis of a subset of the ETS showed that most ETS (84% displayed a distinctive expression pattern in a multi-tissue panel of a lactating cow verifying their existence in the bovine transcriptome. Conclusion The results of our study demonstrate that the exon trapping method based on region-specific BAC clones is very useful for targeted screening for novel transcripts located within a defined chromosomal region being deficiently endowed with annotated gene information. The majority of identified ETS represents unknown noncoding sequences in intergenic regions on BTA6 displaying a

  6. Regional glucose utilization and blood flow in experimental brain tumors studied by double tracer autoradiography

    Energy Technology Data Exchange (ETDEWEB)

    Kato, A.; Sako, K.; Diksic, M.; Yamamoto, Y.L.; Feindel, W.

    1985-01-01

    Coupling of regional glucose utilization (GLU) and blood flow (CBF) was examined in rats with implanted brain tumors (AA ascites tumor) by quantitative double tracer autoradiography using YF-2-fluorodeoxyglucose and 14C-iodoantipyrine. Four to 13 days after implantation, the animals were injected with the two tracers to obtain autoradiograms from the same brain section before and after the decay of YF. The autoradiograms were then analyzed by an image processor to obtain a metabolic coupling index (MCI = GLU/CBF). In the tumor, high GLU and low CBF were uncoupled to give a high MCI which implied anerobic glycolysis. In large tumors, the CBF was even lower. In the peri-tumoral region, GLU was reduced and reduction was lowest around the larger tumors. CBF in the peri-tumoral region was also reduced, but this reduction became less as the distance from the tumor margin increased. The GLU and CBF of white matter was little influenced by the presence of tumors except for some reduction in these values in relation to the larger tumors. The MCI in the tumor was higher than in the cortex of the same as well as the opposite hemisphere. These findings indicate that the metabolism and blood flow of the tumor and surrounding brain are variable and directly related to tumor size.

  7. Benevolent sexism alters executive brain responses.

    Science.gov (United States)

    Dardenne, Benoit; Dumont, Muriel; Sarlet, Marie; Phillips, Christophe; Balteau, Evelyne; Degueldre, Christian; Luxen, André; Salmon, Eric; Maquet, Pierre; Collette, Fabienne

    2013-07-10

    Benevolence is widespread in our societies. It is defined as considering a subordinate group nicely but condescendingly, that is, with charity. Deleterious consequences for the target have been reported in the literature. In this experiment, we used functional MRI (fMRI) to identify whether being the target of (sexist) benevolence induces changes in brain activity associated with a working memory task. Participants were confronted by benevolent, hostile, or neutral comments before and while performing a reading span test in an fMRI environment. fMRI data showed that brain regions associated previously with intrusive thought suppression (bilateral, dorsolateral, prefrontal, and anterior cingulate cortex) reacted specifically to benevolent sexism compared with hostile sexism and neutral conditions during the performance of the task. These findings indicate that, despite being subjectively positive, benevolence modifies task-related brain networks by recruiting supplementary areas likely to impede optimal cognitive performance.

  8. Notch receptor expression in neurogenic regions of the adult zebrafish brain.

    Directory of Open Access Journals (Sweden)

    Vanessa de Oliveira-Carlos

    Full Text Available The adult zebrash brain has a remarkable constitutive neurogenic capacity. The regulation and maintenance of its adult neurogenic niches are poorly understood. In mammals, Notch signaling is involved in stem cell maintenance both in embryonic and adult CNS. To better understand how Notch signaling is involved in stem cell maintenance during adult neurogenesis in zebrafish we analysed Notch receptor expression in five neurogenic zones of the adult zebrafish brain. Combining proliferation and glial markers we identified several subsets of Notch receptor expressing cells. We found that 90 [Formula: see text] of proliferating radial glia express notch1a, notch1b and notch3. In contrast, the proliferating non-glial populations of the dorsal telencephalon and hypothalamus rarely express notch3 and about half express notch1a/1b. In the non-proliferating radial glia notch3 is the predominant receptor throughout the brain. In the ventral telencephalon and in the mitotic area of the optic tectum, where cells have neuroepithelial properties, notch1a/1b/3 are expressed in most proliferating cells. However, in the cerebellar niche, although progenitors also have neuroepithelial properties, only notch1a/1b are expressed in a high number of PCNA [Formula: see text] cells. In this region notch3 expression is mostly in Bergmann glia and at low levels in few PCNA [Formula: see text] cells. Additionally, we found that in the proliferation zone of the ventral telencephalon, Notch receptors display an apical high to basal low gradient of expression. Notch receptors are also expressed in subpopulations of oligodendrocytes, neurons and endothelial cells. We suggest that the partial regional heterogeneity observed for Notch expression in progenitor cells might be related to the cellular diversity present in each of these neurogenic niches.

  9. Region-specific reduction in brain volume in young adults with perinatal hypoxic-ischaemic encephalopathy.

    Science.gov (United States)

    Bregant, Tina; Rados, Milan; Vasung, Lana; Derganc, Metka; Evans, Alan C; Neubauer, David; Kostovic, Ivica

    2013-11-01

    A severe form of perinatal hypoxic-ischaemic encephalopathy (HIE) carries a high risk of perinatal death and severe neurological sequelae while in mild HIE only discrete cognitive disorders may occur. To compare total brain volumes and region-specific cortical measurements between young adults with mild-moderate perinatal HIE and a healthy control group of the same age. MR imaging was performed in a cohort of 14 young adults (9 males, 5 females) with a history of mild or moderate perinatal HIE. The control group consisted of healthy participants, matched with HIE group by age and gender. Volumetric analysis was done after the processing of MR images using a fully automated CIVET pipeline. We measured gyrification indexes, total brain volume, volume of grey and white matter, and of cerebrospinal fluid. We also measured volume, thickness and area of the cerebral cortex in the parietal, occipital, frontal, and temporal lobe, and of the isthmus cinguli, parahippocampal and cingulated gyrus, and insula. The HIE patient group showed smaller absolute volumetric data. Statistically significant (p right hemisphere, of cortical areas in the right temporal lobe and parahippocampal gyrus, of cortical volumes in the right temporal lobe and of cortical thickness in the right isthmus of the cingulate gyrus were found. Comparison between the healthy group and the HIE group of the same gender showed statistically significant changes in the male HIE patients, where a significant reduction was found in whole brain volume; left parietal, bilateral temporal, and right parahippocampal gyrus cortical areas; and bilateral temporal lobe cortical volume. Our analysis of total brain volumes and region-specific corticometric parameters suggests that mild-moderate forms of perinatal HIE lead to reductions in whole brain volumes. In the study reductions were most pronounced in temporal lobe and parahippocampal gyrus. Copyright © 2013 European Paediatric Neurology Society. All rights reserved.

  10. Defining pediatric traumatic brain injury using International Classification of Diseases Version 10 Codes: a systematic review.

    Science.gov (United States)

    Chan, Vincy; Thurairajah, Pravheen; Colantonio, Angela

    2015-02-04

    Although healthcare administrative data are commonly used for traumatic brain injury (TBI) research, there is currently no consensus or consistency on the International Classification of Diseases Version 10 (ICD-10) codes used to define TBI among children and youth internationally. This study systematically reviewed the literature to explore the range of ICD-10 codes that are used to define TBI in this population. The identification of the range of ICD-10 codes to define this population in administrative data is crucial, as it has implications for policy, resource allocation, planning of healthcare services, and prevention strategies. The databases MEDLINE, MEDLINE In-Process, Embase, PsychINFO, CINAHL, SPORTDiscus, and Cochrane Database of Systematic Reviews were systematically searched. Grey literature was searched using Grey Matters and Google. Reference lists of included articles were also searched for relevant studies. Two reviewers independently screened all titles and abstracts using pre-defined inclusion and exclusion criteria. A full text screen was conducted on articles that met the first screen inclusion criteria. All full text articles that met the pre-defined inclusion criteria were included for analysis in this systematic review. A total of 1,326 publications were identified through the predetermined search strategy and 32 articles/reports met all eligibility criteria for inclusion in this review. Five articles specifically examined children and youth aged 19 years or under with TBI. ICD-10 case definitions ranged from the broad injuries to the head codes (ICD-10 S00 to S09) to concussion only (S06.0). There was overwhelming consensus on the inclusion of ICD-10 code S06, intracranial injury, while codes S00 (superficial injury of the head), S03 (dislocation, sprain, and strain of joints and ligaments of head), and S05 (injury of eye and orbit) were only used by articles that examined head injury, none of which specifically examined children and

  11. Enkephalin dipeptidyl carboxypeptidase (enkephalinase) activity: selective radioassay, properties, and regional distribution in human brain

    International Nuclear Information System (INIS)

    Llorens, C.; Malfroy, B.; Schwartz, J.C.; Gacel, G.; Roques, B.P.; Roy, J.; Morgat, J.L.; Javoy-Agid, F.; Agid, Y.

    1982-01-01

    The compound [ 3 H-Tyr 1 ,D-Ala 2 ,Leu-OH 5 ]enkephalin has been synthesised as a potentially selective substrate for enkephalin dipeptidyl carboxypeptidase (enkephalinase) activity in brain. Incubations in the presence of homogenates and particulate fractions from rodent and human brain result in the formation of [ 3 H]Tyr-D-Ala-Gly, which can be conveniently isolated by polystyrene bead column chromatography. The enzyme activity responsible for the hydrolysis of the Gly 3 -Phe 4 amide bond of this substrate displays close resemblance to that hydrolysing the natural enkephalins at the same level. In addition, enkephalinase activity characterised in postmortem human brain is closely similar to that in rodent brain, with regard to optimal pH and apparent affinities of various substrates and inhibitors, including the potent compound thiorphan. Enkephalinase activity is distributed in a highly heterogeneous fashion among regions of human brain, the highest levels being found in globus pallidus and pars reticulata of the substantia nigra. This distribution is poorly correlated with that of opiate receptor binding sites but displays some resemblance to that of reported Met 5 -enkephalin levels. (author)

  12. A cross-sectional MRI study of brain regional atrophy and clinical characteristics of temporal lobe epilepsy with hippocampal sclerosis.

    LENUS (Irish Health Repository)

    2012-02-01

    PURPOSE: Applying a cross-sectional design, we set out to further characterize the significance of extrahippocampal brain atrophy in a large sample of \\'sporadic\\' mesial temporal lobe epilepsy with hippocampal sclerosis (MTLE+HS). By evaluating the influence of epilepsy chronicity on structural atrophy, this work represents an important step towards the characterization of MRI-based volumetric measurements as genetic endophenotypes for this condition. METHODS: Using an automated brain segmentation technique, MRI-based volume measurements of several brain regions were compared between 75 patients with \\'sporadic\\' MTLE+HS and 50 healthy controls. Applying linear regression models, we examined the relationship between structural atrophy and important clinical features of MTLE+HS, including disease duration, lifetime number of partial and generalized seizures, and history of initial precipitating insults (IPIs). RESULTS: Significant volume loss was detected in ipsilateral hippocampus, amygdala, thalamus, and cerebral white matter (WM). In addition, contralateral hippocampal and bilateral cerebellar grey matter (GM) volume loss was observed in left MTLE+HS patients. Hippocampal, amygdalar, and cerebral WM volume loss correlated with duration of epilepsy. This correlation was stronger in patients with prior IPIs history. Further, cerebral WM, cerebellar GM, and contralateral hippocampal volume loss correlated with lifetime number of generalized seizures. CONCLUSION: Our findings confirm that multiple brain regions beyond the hippocampus are involved in the pathogenesis of MTLE+HS. IPIs are an important factor influencing the rate of regional atrophy but our results also support a role for processes related to epilepsy chronicity. The consequence of epilepsy chronicity on candidate brain regions has important implications on their application as genetic endophenotypes.

  13. Brain imaging and brain function

    International Nuclear Information System (INIS)

    Sokoloff, L.

    1985-01-01

    This book is a survey of the applications of imaging studies of regional cerebral blood flow and metabolism to the investigation of neurological and psychiatric disorders. Contributors review imaging techniques and strategies for measuring regional cerebral blood flow and metabolism, for mapping functional neural systems, and for imaging normal brain functions. They then examine the applications of brain imaging techniques to the study of such neurological and psychiatric disorders as: cerebral ischemia; convulsive disorders; cerebral tumors; Huntington's disease; Alzheimer's disease; depression and other mood disorders. A state-of-the-art report on magnetic resonance imaging of the brain and central nervous system rounds out the book's coverage

  14. High permeability cores to optimize the stimulation of deeply located brain regions using transcranial magnetic stimulation

    International Nuclear Information System (INIS)

    Salvador, R; Miranda, P C; Roth, Y; Zangen, A

    2009-01-01

    Efficient stimulation of deeply located brain regions with transcranial magnetic stimulation (TMS) poses many challenges, arising from the fact that the induced field decays rapidly and becomes less focal with depth. We propose a new method to improve the efficiency of TMS of deep brain regions that combines high permeability cores, to increase focality and field intensity, with a coil specifically designed to induce a field that decays slowly with increasing depth. The performance of the proposed design was investigated using the finite element method to determine the total electric field induced by this coil/core arrangement on a realistically shaped homogeneous head model. The calculations show that the inclusion of the cores increases the field's magnitude by as much as 25% while also decreasing the field's decay with depth along specific directions. The focality, as measured by the area where the field's norm is greater than 1/√2 of its maximum value, is also improved by as much as 15% with some core arrangements. The coil's inductance is not significantly increased by the cores. These results show that the presence of the cores might make this specially designed coil even more suited for the effective stimulation of deep brain regions.

  15. High permeability cores to optimize the stimulation of deeply located brain regions using transcranial magnetic stimulation

    Science.gov (United States)

    Salvador, R.; Miranda, P. C.; Roth, Y.; Zangen, A.

    2009-05-01

    Efficient stimulation of deeply located brain regions with transcranial magnetic stimulation (TMS) poses many challenges, arising from the fact that the induced field decays rapidly and becomes less focal with depth. We propose a new method to improve the efficiency of TMS of deep brain regions that combines high permeability cores, to increase focality and field intensity, with a coil specifically designed to induce a field that decays slowly with increasing depth. The performance of the proposed design was investigated using the finite element method to determine the total electric field induced by this coil/core arrangement on a realistically shaped homogeneous head model. The calculations show that the inclusion of the cores increases the field's magnitude by as much as 25% while also decreasing the field's decay with depth along specific directions. The focality, as measured by the area where the field's norm is greater than 1/\\sqrt 2 of its maximum value, is also improved by as much as 15% with some core arrangements. The coil's inductance is not significantly increased by the cores. These results show that the presence of the cores might make this specially designed coil even more suited for the effective stimulation of deep brain regions.

  16. High permeability cores to optimize the stimulation of deeply located brain regions using transcranial magnetic stimulation

    Energy Technology Data Exchange (ETDEWEB)

    Salvador, R; Miranda, P C [Institute of Biophysics and Biomedical Engineering, Faculty of Sciences, University of Lisbon, 1749-016 Lisbon (Portugal); Roth, Y [Advanced Technology Center, Sheba Medical Center, Tel-Hashomer (Israel); Zangen, A [Neurobiology Department, Weizmann Institute of Science, Rehovot 76100 (Israel)], E-mail: rnsalvador@fc.ul.pt

    2009-05-21

    Efficient stimulation of deeply located brain regions with transcranial magnetic stimulation (TMS) poses many challenges, arising from the fact that the induced field decays rapidly and becomes less focal with depth. We propose a new method to improve the efficiency of TMS of deep brain regions that combines high permeability cores, to increase focality and field intensity, with a coil specifically designed to induce a field that decays slowly with increasing depth. The performance of the proposed design was investigated using the finite element method to determine the total electric field induced by this coil/core arrangement on a realistically shaped homogeneous head model. The calculations show that the inclusion of the cores increases the field's magnitude by as much as 25% while also decreasing the field's decay with depth along specific directions. The focality, as measured by the area where the field's norm is greater than 1/{radical}2 of its maximum value, is also improved by as much as 15% with some core arrangements. The coil's inductance is not significantly increased by the cores. These results show that the presence of the cores might make this specially designed coil even more suited for the effective stimulation of deep brain regions.

  17. Transcriptional responses of the nerve agent-sensitive brain regions amygdala, hippocampus, piriform cortex, septum, and thalamus following exposure to the organophosphonate anticholinesterase sarin

    Directory of Open Access Journals (Sweden)

    Meyerhoff James L

    2011-07-01

    Full Text Available Abstract Background Although the acute toxicity of organophosphorus nerve agents is known to result from acetylcholinesterase inhibition, the molecular mechanisms involved in the development of neuropathology following nerve agent-induced seizure are not well understood. To help determine these pathways, we previously used microarray analysis to identify gene expression changes in the rat piriform cortex, a region of the rat brain sensitive to nerve agent exposure, over a 24-h time period following sarin-induced seizure. We found significant differences in gene expression profiles and identified secondary responses that potentially lead to brain injury and cell death. To advance our understanding of the molecular mechanisms involved in sarin-induced toxicity, we analyzed gene expression changes in four other areas of the rat brain known to be affected by nerve agent-induced seizure (amygdala, hippocampus, septum, and thalamus. Methods We compared the transcriptional response of these four brain regions to sarin-induced seizure with the response previously characterized in the piriform cortex. In this study, rats were challenged with 1.0 × LD50 sarin and subsequently treated with atropine sulfate, 2-pyridine aldoxime methylchloride, and diazepam. The four brain regions were collected at 0.25, 1, 3, 6, and 24 h after seizure onset, and total RNA was processed for microarray analysis. Results Principal component analysis identified brain region and time following seizure onset as major sources of variability within the dataset. Analysis of variance identified genes significantly changed following sarin-induced seizure, and gene ontology analysis identified biological pathways, functions, and networks of genes significantly affected by sarin-induced seizure over the 24-h time course. Many of the molecular functions and pathways identified as being most significant across all of the brain regions were indicative of an inflammatory response. There

  18. Region-specific expression of mitochondrial complex I genes during murine brain development.

    Directory of Open Access Journals (Sweden)

    Stefanie Wirtz

    Full Text Available Mutations in the nuclear encoded subunits of mitochondrial complex I (NADH:ubiquinone oxidoreductase may cause circumscribed cerebral lesions ranging from degeneration of the striatal and brainstem gray matter (Leigh syndrome to leukodystrophy. We hypothesized that such pattern of regional pathology might be due to local differences in the dependence on complex I function. Using in situ hybridization we investigated the relative expression of 33 nuclear encoded complex I subunits in different brain regions of the mouse at E11.5, E17.5, P1, P11, P28 and adult (12 weeks. With respect to timing and relative intensity of complex I gene expression we found a highly variant pattern in different regions during development. High average expression levels were detected in periods of intense neurogenesis. In cerebellar Purkinje and in hippocampal CA1/CA3 pyramidal neurons we found a second even higher peak during the period of synaptogenesis and maturation. The extraordinary dependence of these structures on complex I gene expression during synaptogenesis is in accord with our recent findings that gamma oscillations--known to be associated with higher cognitive functions of the mammalian brain--strongly depend on the complex I activity. However, with the exception of the mesencephalon, we detected only average complex I expression levels in the striatum and basal ganglia, which does not explain the exquisite vulnerability of these structures in mitochondrial disorders.

  19. Regional brain response to visual food cues is a marker of satiety that predicts food choice.

    Science.gov (United States)

    Mehta, Sonya; Melhorn, Susan J; Smeraglio, Anne; Tyagi, Vidhi; Grabowski, Thomas; Schwartz, Michael W; Schur, Ellen A

    2012-11-01

    Neuronal processes that underlie the subjective experience of satiety after a meal are not well defined. We investigated how satiety alters the perception of and neural response to visual food cues. Normal-weight participants (10 men, 13 women) underwent 2 fMRI scans while viewing images of high-calorie food that was previously rated as incompatible with weight loss and "fattening" and low-calorie, "nonfattening" food. After a fasting fMRI scan, participants ate a standardized breakfast and underwent reimaging at a randomly assigned time 15-300 min after breakfast to vary the degree of satiety. Measures of subjective appetite, food appeal, and ad libitum food intake (measured after the second fMRI scan) were correlated with activation by "fattening" (compared with "nonfattening") food cues in a priori regions of interest. Greater hunger correlated with higher appeal ratings of "fattening" (r = 0.46, P = 0.03) but not "nonfattening" (r = -0.20, P = 0.37) foods. Fasting amygdalar activation was negatively associated with fullness (left: r = -0.52; right: r = -0.58; both P ≤ 0.01), whereas postbreakfast fullness was positively correlated with activation in the dorsal striatum (right: r = 0.44; left: r = 0.45; both P foods with higher fat content. Postmeal satiety is shown in regional brain activation by images of high-calorie foods. Regions including the amygdala, nucleus accumbens, and dorsal striatum may alter perception of, and reduce motivation to consume, energy-rich foods, ultimately driving food choice. This trial was registered at clinicaltrials.gov as NCT01631045.

  20. The Importance of the Brain Neuro-Programming Technologies in National and Regional Security

    Directory of Open Access Journals (Sweden)

    Vasyl H. Fatkhutdinov

    2018-02-01

    Full Text Available The authors’ understanding of neuro-programming is the result of the impact on the human brain of information and communication technology (including educational one, through which in the human brain the programs of manifestation in the ontogenesis of internal creative potentials are written. This article summarizes the history of the formation of key neuro-programming technologies of the human brain as well as proves that the changes in the society’s worldview are caused by the possibilities and quality of neuro-programming technologies that society uses. Having influence over worldview stereotypes and behaviour set by the society, neuro-programming technologies essentially ensure the national security of any state and the peaceful coexistence of states in the regions and on the planet as a whole. Using historical and philosophical methods, methods of conceptualization, systematization, modeling, etc., the authors have come to the conclusion that the modern world lies in a confrontation of security strategies, in which neuro-programming technologies play a key role.

  1. Mapping the Wolf-Hirschhorn syndrome phenotype outside the currently accepted WHS critical region and defining a new critical region, WHSCR-2.

    Science.gov (United States)

    Zollino, Marcella; Lecce, Rosetta; Fischetto, Rita; Murdolo, Marina; Faravelli, Francesca; Selicorni, Angelo; Buttè, Cinzia; Memo, Luigi; Capovilla, Giuseppe; Neri, Giovanni

    2003-03-01

    In an attempt to define the distinctive Wolf-Hirschhorn syndrome (WHS) phenotype, and to map its specific clinical manifestations, a total of eight patients carrying a 4p16.3 microdeletion were analyzed for their clinical phenotype and their respective genotypes. The extent of each individual deletion was established by fluorescence in situ hybridization, with a cosmid contig spanning the genomic region from MSX1 (distal half of 4p16.1) to the subtelomeric locus D4S3359. The deletions were 1.9-3.5 Mb, and all were terminal. All the patients presented with a mild phenotype, in which major malformations were usually absent. It is worth noting that head circumference was normal for height in two patients (those with the smallest deletions [1.9 and 2.2 Mb]). The currently accepted WHS critical region (WHSCR) was fully preserved in the patient with the 1.9-Mb deletion, in spite of a typical WHS phenotype. The deletion in this patient spanned the chromosome region from D4S3327 (190 b4 cosmid clone included) to the telomere. From a clinical point of view, the distinctive WHS phenotype is defined by the presence of typical facial appearance, mental retardation, growth delay, congenital hypotonia, and seizures. These signs represent the minimal diagnostic criteria for WHS. This basic phenotype maps distal to the currently accepted WHSCR. Here, we propose a new critical region for WHS, and we refer to this region as "WHSCR-2." It falls within a 300-600-kb interval in 4p16.3, between the loci D4S3327 and D4S98-D4S168. Among the candidate genes already described for WHS, LETM1 (leucine zipper/EF-hand-containing transmembrane) is likely to be pathogenetically involved in seizures. On the basis of genotype-phenotype correlation analysis, dividing the WHS phenotype into two distinct clinical entities, a "classical" and a "mild" form, is recommended for the purpose of proper genetic counseling.

  2. Leptin Receptor Deficiency is Associated With Upregulation of Cannabinoid 1 Receptors in Limbic Brain Regions

    Science.gov (United States)

    THANOS, PANAYOTIS K.; RAMALHETE, ROBERTO C.; MICHAELIDES, MICHAEL; PIYIS, YIANNI K.; WANG, GENE-JACK; VOLKOW, NORA D.

    2009-01-01

    Leptin receptor dysfunction results in overeating and obesity. Leptin regulates hypothalamic signaling that underlies the motivation to hyperphagia, but the interaction between leptin and cannabinoid signaling is poorly understood. We evaluated the role of cannabinoid 1 receptors (CB1R) in overeating and the effects of food deprivation on CB1R in the brain. One-month-old Zucker rats were divided into unrestricted and restricted (fed 70% of unrestricted rats) diet groups and maintained until adulthood (4 months). Levels of relative binding sites of CB1R (CB1R binding levels) were assessed using [3H] SR141716A in vitro autoradiography. These levels were higher (except cerebellum and hypothalamus) at 4 months than at 1 month of age. One month CB1R binding levels for most brain regions did not differ between Ob and Lean (Le) rats (except in frontal and cingulate cortices in Le and in the hypothalamus in Ob). Four month Ob rats had higher CB1R binding levels than Le in most brain regions and food restriction was associated with higher CB1R levels in all brain regions in Ob, but not in Le rats. CB1R binding levels increased between adolescence and young adulthood which we believe was influenced by leptin and food availability. The high levels of CB1R in Ob rats suggest that leptin's inhibition of food-intake is in part mediated by downregulation of CB1R and that leptin interferes with CB1R upregulation under food-deprivation conditions. These results are consistent with prior findings showing increased levels of endogenous cannabinoids in the Ob rats corroborating the regulation of cannabinoid signaling by leptin. PMID:18563836

  3. Region-specific RNA m6A methylation represents a new layer of control in the gene regulatory network in the mouse brain.

    Science.gov (United States)

    Chang, Mengqi; Lv, Hongyi; Zhang, Weilong; Ma, Chunhui; He, Xue; Zhao, Shunli; Zhang, Zhi-Wei; Zeng, Yi-Xin; Song, Shuhui; Niu, Yamei; Tong, Wei-Min

    2017-09-01

    N 6 -methyladenosine (m 6 A) is the most abundant epitranscriptomic mark found on mRNA and has important roles in various physiological processes. Despite the relatively high m 6 A levels in the brain, its potential functions in the brain remain largely unexplored. We performed a transcriptome-wide methylation analysis using the mouse brain to depict its region-specific methylation profile. RNA methylation levels in mouse cerebellum are generally higher than those in the cerebral cortex. Heterogeneity of RNA methylation exists across different brain regions and different types of neural cells including the mRNAs to be methylated, their methylation levels and methylation site selection. Common and region-specific methylation have different preferences for methylation site selection and thereby different impacts on their biological functions. In addition, high methylation levels of fragile X mental retardation protein (FMRP) target mRNAs suggest that m 6 A methylation is likely to be used for selective recognition of target mRNAs by FMRP in the synapse. Overall, we provide a region-specific map of RNA m 6 A methylation and characterize the distinct features of specific and common methylation in mouse cerebellum and cerebral cortex. Our results imply that RNA m 6 A methylation is a newly identified element in the region-specific gene regulatory network in the mouse brain. © 2017 The Authors.

  4. Incorporating 3D-printing technology in the design of head-caps and electrode drives for recording neurons in multiple brain regions.

    Science.gov (United States)

    Headley, Drew B; DeLucca, Michael V; Haufler, Darrell; Paré, Denis

    2015-04-01

    Recent advances in recording and computing hardware have enabled laboratories to record the electrical activity of multiple brain regions simultaneously. Lagging behind these technical advances, however, are the methods needed to rapidly produce microdrives and head-caps that can flexibly accommodate different recording configurations. Indeed, most available designs target single or adjacent brain regions, and, if multiple sites are targeted, specially constructed head-caps are used. Here, we present a novel design style, for both microdrives and head-caps, which takes advantage of three-dimensional printing technology. This design facilitates targeting of multiple brain regions in various configurations. Moreover, the parts are easily fabricated in large quantities, with only minor hand-tooling and finishing required. Copyright © 2015 the American Physiological Society.

  5. Stability of whole brain and regional network topology within and between resting and cognitive states.

    Science.gov (United States)

    Rzucidlo, Justyna K; Roseman, Paige L; Laurienti, Paul J; Dagenbach, Dale

    2013-01-01

    Graph-theory based analyses of resting state functional Magnetic Resonance Imaging (fMRI) data have been used to map the network organization of the brain. While numerous analyses of resting state brain organization exist, many questions remain unexplored. The present study examines the stability of findings based on this approach over repeated resting state and working memory state sessions within the same individuals. This allows assessment of stability of network topology within the same state for both rest and working memory, and between rest and working memory as well. fMRI scans were performed on five participants while at rest and while performing the 2-back working memory task five times each, with task state alternating while they were in the scanner. Voxel-based whole brain network analyses were performed on the resulting data along with analyses of functional connectivity in regions associated with resting state and working memory. Network topology was fairly stable across repeated sessions of the same task, but varied significantly between rest and working memory. In the whole brain analysis, local efficiency, Eloc, differed significantly between rest and working memory. Analyses of network statistics for the precuneus and dorsolateral prefrontal cortex revealed significant differences in degree as a function of task state for both regions and in local efficiency for the precuneus. Conversely, no significant differences were observed across repeated sessions of the same state. These findings suggest that network topology is fairly stable within individuals across time for the same state, but also fluid between states. Whole brain voxel-based network analyses may prove to be a valuable tool for exploring how functional connectivity changes in response to task demands.

  6. Neuroimaging meta-analysis of cannabis use studies reveals convergent functional alterations in brain regions supporting cognitive control and reward processing.

    Science.gov (United States)

    Yanes, Julio A; Riedel, Michael C; Ray, Kimberly L; Kirkland, Anna E; Bird, Ryan T; Boeving, Emily R; Reid, Meredith A; Gonzalez, Raul; Robinson, Jennifer L; Laird, Angela R; Sutherland, Matthew T

    2018-03-01

    Lagging behind rapid changes to state laws, societal views, and medical practice is the scientific investigation of cannabis's impact on the human brain. While several brain imaging studies have contributed important insight into neurobiological alterations linked with cannabis use, our understanding remains limited. Here, we sought to delineate those brain regions that consistently demonstrate functional alterations among cannabis users versus non-users across neuroimaging studies using the activation likelihood estimation meta-analysis framework. In ancillary analyses, we characterized task-related brain networks that co-activate with cannabis-affected regions using data archived in a large neuroimaging repository, and then determined which psychological processes may be disrupted via functional decoding techniques. When considering convergent alterations among users, decreased activation was observed in the anterior cingulate cortex, which co-activated with frontal, parietal, and limbic areas and was linked with cognitive control processes. Similarly, decreased activation was observed in the dorsolateral prefrontal cortex, which co-activated with frontal and occipital areas and linked with attention-related processes. Conversely, increased activation among users was observed in the striatum, which co-activated with frontal, parietal, and other limbic areas and linked with reward processing. These meta-analytic outcomes indicate that cannabis use is linked with differential, region-specific effects across the brain.

  7. Tartrazine induced neurobiochemical alterations in rat brain sub-regions.

    Science.gov (United States)

    Bhatt, Diksha; Vyas, Krati; Singh, Shakuntala; John, P J; Soni, Inderpal

    2018-03-01

    Tartrazine is a synthetic lemon yellow azo dye primarily used as a food coloring. The present study aimed to screen the neurobiochemical effects of Tartrazine in Wistar rats after administering the Acceptable Daily Intake (ADI) level. Tartrazine (7.5 mg/kg b.w.) was administered to 21 day old weanling rats through oral gavage once daily for 40 consecutive days. On 41st day, the animals were sacrificed and brain sub regions namely, frontal cortex, corpus striatum, hippocampus and cerebellum were used to determine activities of anti-oxidant enzymes viz. Superoxide Dismutase (SOD), Catalase (CAT), Glutathione-Stransferase (GST), Glutathione Reductase (GR) and Glutathione Peroxidase (GPx) and levels of lipid peroxides using Thio-barbituric Acid Reactive Substance (TBARS) assay. Our investigation showed a significant decrease in SOD and CAT activity, whereas there occurred a decline in GST and GR activity with an increase in GPx activity to counteract the oxidative damage caused by significantly increased levels of lipid peroxides. The possible mechanism of this oxidative damage might be attributed to the production of sulphanilc acid as a metabolite in azofission of tartrazine. It may be concluded that the ADI levels of food azo dyes adversely affect and alter biochemical markers of brain tissue and cause oxidative damage. Copyright © 2018 Elsevier Ltd. All rights reserved.

  8. Brain anatomical networks in early human brain development.

    Science.gov (United States)

    Fan, Yong; Shi, Feng; Smith, Jeffrey Keith; Lin, Weili; Gilmore, John H; Shen, Dinggang

    2011-02-01

    Recent neuroimaging studies have demonstrated that human brain networks have economic small-world topology and modular organization, enabling efficient information transfer among brain regions. However, it remains largely unknown how the small-world topology and modular organization of human brain networks emerge and develop. Using longitudinal MRI data of 28 healthy pediatric subjects, collected at their ages of 1 month, 1 year, and 2 years, we analyzed development patterns of brain anatomical networks derived from morphological correlations of brain regional volumes. The results show that the brain network of 1-month-olds has the characteristically economic small-world topology and nonrandom modular organization. The network's cost efficiency increases with the brain development to 1 year and 2 years, so does the modularity, providing supportive evidence for the hypothesis that the small-world topology and the modular organization of brain networks are established during early brain development to support rapid synchronization and information transfer with minimal rewiring cost, as well as to balance between local processing and global integration of information. Copyright © 2010. Published by Elsevier Inc.

  9. Multichannel brain recordings in behaving Drosophila reveal oscillatory activity and local coherence in response to sensory stimulation and circuit activation.

    Science.gov (United States)

    Paulk, Angelique C; Zhou, Yanqiong; Stratton, Peter; Liu, Li; van Swinderen, Bruno

    2013-10-01

    Neural networks in vertebrates exhibit endogenous oscillations that have been associated with functions ranging from sensory processing to locomotion. It remains unclear whether oscillations may play a similar role in the insect brain. We describe a novel "whole brain" readout for Drosophila melanogaster using a simple multichannel recording preparation to study electrical activity across the brain of flies exposed to different sensory stimuli. We recorded local field potential (LFP) activity from >2,000 registered recording sites across the fly brain in >200 wild-type and transgenic animals to uncover specific LFP frequency bands that correlate with: 1) brain region; 2) sensory modality (olfactory, visual, or mechanosensory); and 3) activity in specific neural circuits. We found endogenous and stimulus-specific oscillations throughout the fly brain. Central (higher-order) brain regions exhibited sensory modality-specific increases in power within narrow frequency bands. Conversely, in sensory brain regions such as the optic or antennal lobes, LFP coherence, rather than power, best defined sensory responses across modalities. By transiently activating specific circuits via expression of TrpA1, we found that several circuits in the fly brain modulate LFP power and coherence across brain regions and frequency domains. However, activation of a neuromodulatory octopaminergic circuit specifically increased neuronal coherence in the optic lobes during visual stimulation while decreasing coherence in central brain regions. Our multichannel recording and brain registration approach provides an effective way to track activity simultaneously across the fly brain in vivo, allowing investigation of functional roles for oscillations in processing sensory stimuli and modulating behavior.

  10. Effect of time period after boric acid injection on {sup 10}B absorption in different regions of adult male rat's brain

    Energy Technology Data Exchange (ETDEWEB)

    Baghban Khojasteh, Nasrin, E-mail: khojasteh.nasrin@gmail.com [Nuclear Engineering Department, Science and Research Branch, Islamic Azad University, Poonak Sq. PO Box 14515-775, Tehran (Iran, Islamic Republic of); Pazirandeh, Ali [Nuclear Engineering Department, Science and Research Branch, Islamic Azad University, Poonak Sq. PO Box 14515-775, Tehran (Iran, Islamic Republic of); Jameie, Behnam [Nuclear Engineering Department, Science and Research Branch, Islamic Azad University, Poonak Sq. PO Box 14515-775, Tehran (Iran, Islamic Republic of); Laboratory of Basic Science and Neuroscience, Basic Science Dept, Faculty of Allied Medicine, Cellular and Molecular Research Center, Tehran University of Medical Science, Pardis-e-Hemmat,Tehran (Iran, Islamic Republic of); Goodarzi, Samereh [Nuclear Engineering Department, Science and Research Branch, Islamic Azad University, Poonak Sq. PO Box 14515-775, Tehran (Iran, Islamic Republic of)

    2012-06-15

    Distribution of {sup 10}B in different regions of rat normal brain was studied. Two groups were chosen as control and trial. Trial group received 2 ml of neutral boron compound. 2, 4 and 6 h after the injection brain removed, coronal sections of forebrain, midbrain and hindbrain were sandwiched between two pieces of polycarbonate. Autoradiography plots of {sup 10}B distribution showed significant differences in three regions with the highest {sup 10}B concentration in the forebrain during 4 h after injection. - Highlights: Black-Right-Pointing-Pointer Normal tissue tolerance is very important in BNCT. Black-Right-Pointing-Pointer This study has been done to determine {sup 10}B distribution in three anatomical regions of rat normal brain. Black-Right-Pointing-Pointer These specific regions of brain have not been studied in previous BNCT projects. Black-Right-Pointing-Pointer We found significant differences in {sup 10}B distribution between these three regions. Black-Right-Pointing-Pointer In different time periods after neutral boron compound injection, there has been a significant difference in boron absorption.

  11. Landmark-based deep multi-instance learning for brain disease diagnosis.

    Science.gov (United States)

    Liu, Mingxia; Zhang, Jun; Adeli, Ehsan; Shen, Dinggang

    2018-01-01

    In conventional Magnetic Resonance (MR) image based methods, two stages are often involved to capture brain structural information for disease diagnosis, i.e., 1) manually partitioning each MR image into a number of regions-of-interest (ROIs), and 2) extracting pre-defined features from each ROI for diagnosis with a certain classifier. However, these pre-defined features often limit the performance of the diagnosis, due to challenges in 1) defining the ROIs and 2) extracting effective disease-related features. In this paper, we propose a landmark-based deep multi-instance learning (LDMIL) framework for brain disease diagnosis. Specifically, we first adopt a data-driven learning approach to discover disease-related anatomical landmarks in the brain MR images, along with their nearby image patches. Then, our LDMIL framework learns an end-to-end MR image classifier for capturing both the local structural information conveyed by image patches located by landmarks and the global structural information derived from all detected landmarks. We have evaluated our proposed framework on 1526 subjects from three public datasets (i.e., ADNI-1, ADNI-2, and MIRIAD), and the experimental results show that our framework can achieve superior performance over state-of-the-art approaches. Copyright © 2017 Elsevier B.V. All rights reserved.

  12. Correlations between regional cerebral blood flow and age-related brain atrophy: a quantitative study with computed tomography and the xenon-133 inhalation method

    International Nuclear Information System (INIS)

    Yamaguchi, T.; Hatazawa, J.; Kubota, K.; Abe, Y.; Fujiwara, T.; Matsuzawa, T.

    1983-01-01

    One hundred and two subjects (40 men and 62 women) neither having a history of neurologic deficits nor showing organic lesions on computed tomographic examination of the brain were studied. Ages of the subjects ranged from 26 to 81 years. Regional cerebral blood flow was measured by the xenon-133 inhalation method, and the volume percentage of brain with respect to the cranial cavity (craniocerebral index) was calculated by means of computer programs. Regional cerebral blood flow was computed as the fast component of two-compartmental analysis and as the initial slope index value. The percentage of each subject's craniocerebral index in relation to the standard for subjects with non-atrophied brains (brain volume index) was calculated as the indicator of brain atrophy. Both the mean brain fast component values and the mean brain initial slope index values correlated closely with the brain volume index in the elderly. Low cerebral blood flow values coincided with loss of brain substance in the final stage of age-related brain atrophy, but not in the intermediate stage

  13. Selective constraints in experimentally defined primate regulatory regions.

    Directory of Open Access Journals (Sweden)

    Daniel J Gaffney

    2008-08-01

    Full Text Available Changes in gene regulation may be important in evolution. However, the evolutionary properties of regulatory mutations are currently poorly understood. This is partly the result of an incomplete annotation of functional regulatory DNA in many species. For example, transcription factor binding sites (TFBSs, a major component of eukaryotic regulatory architecture, are typically short, degenerate, and therefore difficult to differentiate from randomly occurring, nonfunctional sequences. Furthermore, although sites such as TFBSs can be computationally predicted using evolutionary conservation as a criterion, estimates of the true level of selective constraint (defined as the fraction of strongly deleterious mutations occurring at a locus in regulatory regions will, by definition, be upwardly biased in datasets that are a priori evolutionarily conserved. Here we investigate the fitness effects of regulatory mutations using two complementary datasets of human TFBSs that are likely to be relatively free of ascertainment bias with respect to evolutionary conservation but, importantly, are supported by experimental data. The first is a collection of almost >2,100 human TFBSs drawn from the literature in the TRANSFAC database, and the second is derived from several recent high-throughput chromatin immunoprecipitation coupled with genomic microarray (ChIP-chip analyses. We also define a set of putative cis-regulatory modules (pCRMs by spatially clustering multiple TFBSs that regulate the same gene. We find that a relatively high proportion ( approximately 37% of mutations at TFBSs are strongly deleterious, similar to that at a 2-fold degenerate protein-coding site. However, constraint is significantly reduced in human and chimpanzee pCRMS and ChIP-chip sequences, relative to macaques. We estimate that the fraction of regulatory mutations that have been driven to fixation by positive selection in humans is not significantly different from zero. We also find

  14. Brain reward region responsivity of adolescents with and without parental substance use disorders.

    Science.gov (United States)

    Stice, Eric; Yokum, Sonja

    2014-09-01

    The present study tested the competing hypotheses that adolescents at risk for future substance abuse and dependence by virtue of parental substance use disorders show either weaker or stronger responsivity of brain regions implicated in reward relative to youth without parental history of substance use disorders. Adolescents (n = 52) matched on demographics with and without parental substance use disorders, as determined by diagnostic interviews, who denied substance use in the past year were compared on functional MRI (fMRI) paradigms assessing neural response to receipt and anticipated receipt of monetary and food reward. Parental-history-positive versus -negative adolescents showed greater activation in the left dorsolateral prefrontal cortex and bilateral putamen, and less activation in the fusiform gyrus and inferior temporal gyrus in response to anticipating winning money, as well as greater activation in the left midbrain and right paracentral lobule, and less activation in the right middle frontal gyrus in response to milkshake receipt. Results indicate that adolescents at risk for future onset of substance use disorders show elevated responsivity of brain regions implicated in reward, extending results from 2 smaller prior studies that found that individuals with versus without parental alcohol use disorders showed greater reward region response to anticipated monetary reward and pictures of alcohol. Collectively, results provide support for the reward surfeit model of substance use disorders, rather than the reward deficit model.

  15. Brain activity dynamics in human parietal regions during spontaneous switches in bistable perception.

    Science.gov (United States)

    Megumi, Fukuda; Bahrami, Bahador; Kanai, Ryota; Rees, Geraint

    2015-02-15

    The neural mechanisms underlying conscious visual perception have been extensively investigated using bistable perception paradigms. Previous functional magnetic resonance imaging (fMRI) and transcranial magnetic stimulation (TMS) studies suggest that the right anterior superior parietal (r-aSPL) and the right posterior superior parietal lobule (r-pSPL) have opposite roles in triggering perceptual reversals. It has been proposed that these two areas are part of a hierarchical network whose dynamics determine perceptual switches. However, how these two parietal regions interact with each other and with the rest of the brain during bistable perception is not known. Here, we investigated such a model by recording brain activity using fMRI while participants viewed a bistable structure-from-motion stimulus. Using dynamic causal modeling (DCM), we found that resolving such perceptual ambiguity was specifically associated with reciprocal interactions between these parietal regions and V5/MT. Strikingly, the strength of bottom-up coupling between V5/MT to r-pSPL and from r-pSPL to r-aSPL predicted individual mean dominance duration. Our findings are consistent with a hierarchical predictive coding model of parietal involvement in bistable perception and suggest that visual information processing underlying spontaneous perceptual switches can be described as changes in connectivity strength between parietal and visual cortical regions. Copyright © 2014 The Authors. Published by Elsevier Inc. All rights reserved.

  16. Mitochondrial Complex 1 Activity Measured by Spectrophotometry Is Reduced across All Brain Regions in Ageing and More Specifically in Neurodegeneration.

    Science.gov (United States)

    Pollard, Amelia Kate; Craig, Emma Louise; Chakrabarti, Lisa

    2016-01-01

    Mitochondrial function, in particular complex 1 of the electron transport chain (ETC), has been shown to decrease during normal ageing and in neurodegenerative disease. However, there is some debate concerning which area of the brain has the greatest complex 1 activity. It is important to identify the pattern of activity in order to be able to gauge the effect of age or disease related changes. We determined complex 1 activity spectrophotometrically in the cortex, brainstem and cerebellum of middle aged mice (70-71 weeks), a cerebellar ataxic neurodegeneration model (pcd5J) and young wild type controls. We share our updated protocol on the measurements of complex1 activity and find that mitochondrial fractions isolated from frozen tissues can be measured for robust activity. We show that complex 1 activity is clearly highest in the cortex when compared with brainstem and cerebellum (p<0.003). Cerebellum and brainstem mitochondria exhibit similar levels of complex 1 activity in wild type brains. In the aged brain we see similar levels of complex 1 activity in all three-brain regions. The specific activity of complex 1 measured in the aged cortex is significantly decreased when compared with controls (p<0.0001). Both the cerebellum and brainstem mitochondria also show significantly reduced activity with ageing (p<0.05). The mouse model of ataxia predictably has a lower complex 1 activity in the cerebellum, and although reductions are measured in the cortex and brain stem, the remaining activity is higher than in the aged brains. We present clear evidence that complex 1 activity decreases across the brain with age and much more specifically in the cerebellum of the pcd5j mouse. Mitochondrial impairment can be a region specific phenomenon in disease, but in ageing appears to affect the entire brain, abolishing the pattern of higher activity in cortical regions.

  17. Structural brain connectivity and cognitive ability differences: A multivariate distance matrix regression analysis.

    Science.gov (United States)

    Ponsoda, Vicente; Martínez, Kenia; Pineda-Pardo, José A; Abad, Francisco J; Olea, Julio; Román, Francisco J; Barbey, Aron K; Colom, Roberto

    2017-02-01

    Neuroimaging research involves analyses of huge amounts of biological data that might or might not be related with cognition. This relationship is usually approached using univariate methods, and, therefore, correction methods are mandatory for reducing false positives. Nevertheless, the probability of false negatives is also increased. Multivariate frameworks have been proposed for helping to alleviate this balance. Here we apply multivariate distance matrix regression for the simultaneous analysis of biological and cognitive data, namely, structural connections among 82 brain regions and several latent factors estimating cognitive performance. We tested whether cognitive differences predict distances among individuals regarding their connectivity pattern. Beginning with 3,321 connections among regions, the 36 edges better predicted by the individuals' cognitive scores were selected. Cognitive scores were related to connectivity distances in both the full (3,321) and reduced (36) connectivity patterns. The selected edges connect regions distributed across the entire brain and the network defined by these edges supports high-order cognitive processes such as (a) (fluid) executive control, (b) (crystallized) recognition, learning, and language processing, and (c) visuospatial processing. This multivariate study suggests that one widespread, but limited number, of regions in the human brain, supports high-level cognitive ability differences. Hum Brain Mapp 38:803-816, 2017. © 2016 Wiley Periodicals, Inc. © 2016 Wiley Periodicals, Inc.

  18. Opiate antagonist binding sites in discrete brain regions of spontaneously hypertensive and normotensive Wistar-Kyoto rats

    International Nuclear Information System (INIS)

    Rahmani, N.H.; Gulati, A.; Bhargava, H.N.

    1991-01-01

    The binding of 3 H-naltrexone, an opiate receptor antagonist, to membranes of discrete brain regions and spinal cord of 10 week old spontaneously hypertensive (SHR) and normotensive Wistar-Kyoto (WKY) rats was determined. The brain regions examined were hypothalamus, amygdala, hippocampus, corpus striatum, pons and medulla, midbrain and cortex. 3 H-Naltrexone bound to membranes of brain regions and spinal cord at a single high affinity site with an apparent dissociation constant value of 3 nM. The highest density of 3 H-naltrexone binding sites were in hippocampus and lowest in the cerebral cortex. The receptor density (B max value) and apparent dissociation constant (K d value) values of 3 H-naltrexone to bind to opiate receptors on the membranes of amygdala, hippocampus, corpus striatum, pons and medulla, midgrain, cortex and spinal cord of WKY and SHR rates did not differ. The B max value of 3 H-naltrexone binding to membranes of hypothalamus of SHR rates was 518% higher than WKY rats but the K d values in the two strains did not differ. It is concluded that SHR rats have higher density of opiate receptors labeled with 3 H-naltrexone in the hypothalamus only, in comparison with WKY rats, and that such a difference in the density of opiate receptors may be related to the elevated blood pressure in SHR rats

  19. Multichannel brain recordings in behaving Drosophila reveal oscillatory activity and local coherence in response to sensory stimulation and circuit activation

    Science.gov (United States)

    Paulk, Angelique C.; Zhou, Yanqiong; Stratton, Peter; Liu, Li

    2013-01-01

    Neural networks in vertebrates exhibit endogenous oscillations that have been associated with functions ranging from sensory processing to locomotion. It remains unclear whether oscillations may play a similar role in the insect brain. We describe a novel “whole brain” readout for Drosophila melanogaster using a simple multichannel recording preparation to study electrical activity across the brain of flies exposed to different sensory stimuli. We recorded local field potential (LFP) activity from >2,000 registered recording sites across the fly brain in >200 wild-type and transgenic animals to uncover specific LFP frequency bands that correlate with: 1) brain region; 2) sensory modality (olfactory, visual, or mechanosensory); and 3) activity in specific neural circuits. We found endogenous and stimulus-specific oscillations throughout the fly brain. Central (higher-order) brain regions exhibited sensory modality-specific increases in power within narrow frequency bands. Conversely, in sensory brain regions such as the optic or antennal lobes, LFP coherence, rather than power, best defined sensory responses across modalities. By transiently activating specific circuits via expression of TrpA1, we found that several circuits in the fly brain modulate LFP power and coherence across brain regions and frequency domains. However, activation of a neuromodulatory octopaminergic circuit specifically increased neuronal coherence in the optic lobes during visual stimulation while decreasing coherence in central brain regions. Our multichannel recording and brain registration approach provides an effective way to track activity simultaneously across the fly brain in vivo, allowing investigation of functional roles for oscillations in processing sensory stimuli and modulating behavior. PMID:23864378

  20. Regional ADC values of the normal brain: differences due to age, gender, and laterality

    Energy Technology Data Exchange (ETDEWEB)

    Naganawa, Shinji; Ishigaki, Takeo [Department of Radiology, Nagoya University School of Medicine, 65 Tsurumai-cho, Shouwa-ku, Nagoya 466-8550 (Japan); Sato, Kimihide; Katagiri, Toshio; Mimura, Takeo [Department of Radiology, First Kamiida General Hospital (Japan)

    2003-01-01

    The purpose of this study was to evaluate the stability of measurement for apparent diffusion coefficient (ADC) values in normal brain, to clarify the effect of aging on ADC values, to compare ADC values between men and women, and to compare ADC values between right and left sides of the brain. To evaluate the stability of measurements, five normal volunteers (four men and one woman) were examined five times on different days. Then, 294 subjects with normal MR imaging (147 men and 147 women; age range 20-89 years) were measured. The ADC measurement in normal volunteers was stable. The ADC values stayed within the 5% deviation of average values in all volunteers (mean{+-}standard deviation 2.3{+-}1.2%). The ADC values gradually increased by aging in all regions. In thalamus, no significant difference was seen between right and left in the subjects under 60 years; however, right side showed higher values in the subjects over 60 years (p<0.01). In the subjects under 60 years, women showed higher values in right frontal, bilateral thalamus, and temporal (p<0.01); however, in the subjects over 60 years, no region showed difference between men and women. The knowledge obtained in this study may be helpful to understand the developmental and aging mechanisms of normal brain and may be useful for the future quantitative study as a reference. (orig.)

  1. Regional ADC values of the normal brain: differences due to age, gender, and laterality

    International Nuclear Information System (INIS)

    Naganawa, Shinji; Ishigaki, Takeo; Sato, Kimihide; Katagiri, Toshio; Mimura, Takeo

    2003-01-01

    The purpose of this study was to evaluate the stability of measurement for apparent diffusion coefficient (ADC) values in normal brain, to clarify the effect of aging on ADC values, to compare ADC values between men and women, and to compare ADC values between right and left sides of the brain. To evaluate the stability of measurements, five normal volunteers (four men and one woman) were examined five times on different days. Then, 294 subjects with normal MR imaging (147 men and 147 women; age range 20-89 years) were measured. The ADC measurement in normal volunteers was stable. The ADC values stayed within the 5% deviation of average values in all volunteers (mean±standard deviation 2.3±1.2%). The ADC values gradually increased by aging in all regions. In thalamus, no significant difference was seen between right and left in the subjects under 60 years; however, right side showed higher values in the subjects over 60 years (p<0.01). In the subjects under 60 years, women showed higher values in right frontal, bilateral thalamus, and temporal (p<0.01); however, in the subjects over 60 years, no region showed difference between men and women. The knowledge obtained in this study may be helpful to understand the developmental and aging mechanisms of normal brain and may be useful for the future quantitative study as a reference. (orig.)

  2. Regional Brain Glucose Hypometabolism in Young Women with Polycystic Ovary Syndrome: Possible Link to Mild Insulin Resistance.

    Science.gov (United States)

    Castellano, Christian-Alexandre; Baillargeon, Jean-Patrice; Nugent, Scott; Tremblay, Sébastien; Fortier, Mélanie; Imbeault, Hélène; Duval, Julie; Cunnane, Stephen C

    2015-01-01

    To investigate whether cerebral metabolic rate of glucose (CMRglu) is altered in normal weight young women with polycystic ovary syndrome (PCOS) who exhibit mild insulin resistance. Seven women with PCOS were compared to eleven healthy female controls of similar age, education and body mass index. Regional brain glucose uptake was quantified using FDG with dynamic positron emission tomography and magnetic resonance imaging, and its potential relationship with insulin resistance assessed using the updated homeostasis model assessment (HOMA2-IR). A battery of cognitive tests was administered to evaluate working memory, attention and executive function. The PCOS group had 10% higher fasting glucose and 40% higher HOMA2-IR (p ≤ 0.035) compared to the Controls. The PCOS group had 9-14% lower CMRglu in specific regions of the frontal, parietal and temporal cortices (p ≤ 0.018). A significant negative relation was found between the CMRglu and HOMA2-IR mainly in the frontal, parietal and temporal cortices as well as in the hippocampus and the amygdala (p ≤ 0.05). Globally, cognitive performance was normal in both groups but scores on the PASAT test of working memory tended to be low in the PCOS group. The PCOS group exhibited a pattern of low regional CMRglu that correlated inversely with HOMA2-IR in several brain regions and which resembled the pattern seen in aging and early Alzheimer's disease. These results suggest that a direct association between mild insulin resistance and brain glucose hypometabolism independent of overweight or obesity can exist in young adults in their 20s. Further investigation of the influence of insulin resistance on brain glucose metabolism and cognition in younger and middle-aged adults is warranted.

  3. Regional Brain Glucose Hypometabolism in Young Women with Polycystic Ovary Syndrome: Possible Link to Mild Insulin Resistance.

    Directory of Open Access Journals (Sweden)

    Christian-Alexandre Castellano

    Full Text Available To investigate whether cerebral metabolic rate of glucose (CMRglu is altered in normal weight young women with polycystic ovary syndrome (PCOS who exhibit mild insulin resistance.Seven women with PCOS were compared to eleven healthy female controls of similar age, education and body mass index. Regional brain glucose uptake was quantified using FDG with dynamic positron emission tomography and magnetic resonance imaging, and its potential relationship with insulin resistance assessed using the updated homeostasis model assessment (HOMA2-IR. A battery of cognitive tests was administered to evaluate working memory, attention and executive function.The PCOS group had 10% higher fasting glucose and 40% higher HOMA2-IR (p ≤ 0.035 compared to the Controls. The PCOS group had 9-14% lower CMRglu in specific regions of the frontal, parietal and temporal cortices (p ≤ 0.018. A significant negative relation was found between the CMRglu and HOMA2-IR mainly in the frontal, parietal and temporal cortices as well as in the hippocampus and the amygdala (p ≤ 0.05. Globally, cognitive performance was normal in both groups but scores on the PASAT test of working memory tended to be low in the PCOS group.The PCOS group exhibited a pattern of low regional CMRglu that correlated inversely with HOMA2-IR in several brain regions and which resembled the pattern seen in aging and early Alzheimer's disease. These results suggest that a direct association between mild insulin resistance and brain glucose hypometabolism independent of overweight or obesity can exist in young adults in their 20s. Further investigation of the influence of insulin resistance on brain glucose metabolism and cognition in younger and middle-aged adults is warranted.

  4. Impaired Associative Taste Learning and Abnormal Brain Activation in Kinase-Defective eEF2K Mice

    Science.gov (United States)

    Gildish, Iness; Manor, David; David, Orit; Sharma, Vijendra; Williams, David; Agarwala, Usha; Wang, Xuemin; Kenney, Justin W.; Proud, Chris G.; Rosenblum, Kobi

    2012-01-01

    Memory consolidation is defined temporally based on pharmacological interventions such as inhibitors of mRNA translation (molecular consolidation) or post-acquisition deactivation of specific brain regions (systems level consolidation). However, the relationship between molecular and systems consolidation are poorly understood. Molecular…

  5. Training of verbal creativity modulates brain activity in regions associated with language- and memory-related demands.

    Science.gov (United States)

    Fink, Andreas; Benedek, Mathias; Koschutnig, Karl; Pirker, Eva; Berger, Elisabeth; Meister, Sabrina; Neubauer, Aljoscha C; Papousek, Ilona; Weiss, Elisabeth M

    2015-10-01

    This functional magnetic resonance (fMRI) study was designed to investigate changes in functional patterns of brain activity during creative ideation as a result of a computerized, 3-week verbal creativity training. The training was composed of various verbal divergent thinking exercises requiring participants to train approximately 20 min per day. Fifty-three participants were tested three times (psychometric tests and fMRI assessment) with an intertest-interval of 4 weeks each. Participants were randomly assigned to two different training groups, which received the training time-delayed: The first training group was trained between the first and the second test, while the second group accomplished the training between the second and the third test session. At the behavioral level, only one training group showed improvements in different facets of verbal creativity right after the training. Yet, functional patterns of brain activity during creative ideation were strikingly similar across both training groups. Whole-brain voxel-wise analyses (along with supplementary region of interest analyses) revealed that the training was associated with activity changes in well-known creativity-related brain regions such as the left inferior parietal cortex and the left middle temporal gyrus, which have been shown as being particularly sensitive to the originality facet of creativity in previous research. Taken together, this study demonstrates that continuous engagement in a specific complex cognitive task like divergent thinking is associated with reliable changes of activity patterns in relevant brain areas, suggesting more effective search, retrieval, and integration from internal memory representations as a result of the training. © 2015 Wiley Periodicals, Inc.

  6. Spatial distribution of resting-state BOLD regional homogeneity as a predictor of brain glucose uptake: A study in healthy aging.

    Science.gov (United States)

    Bernier, Michaël; Croteau, Etienne; Castellano, Christian-Alexandre; Cunnane, Stephen C; Whittingstall, Kevin

    2017-04-15

    Positron emission tomography using [18F]-fluorodeoxyglucose (PET-FDG) is the primary imaging modality used to measure glucose metabolism in the brain (CMRGlu). CMRGlu has been used as a biomarker of brain aging and neurodegenerative diseases, but the complexity and invasive nature of PET often limits its use in research. There is therefore great interest in developing non-invasive metrics for estimating brain CMRGlu. We therefore investigated resting state fMRI metrics such as regional homogeneity (ReHo), amplitude of low-frequency fluctuations (ALFF) and regional global connectivity (Closeness) with multiple analytical approaches to determine their relationship to CMRGlu. We investigated this relation in two distinct cognitively healthy populations separated by age (27 young adults and 35 older adults). Overall, we found that both regionally and across participants, ReHo strongly correlated with CMRGlu in healthy young and older adults. Moreover, ReHo demonstrated the same age-related differences as CMRGlu throughout all cortical regions, particularly in the default network and frontal areas. Copyright © 2017 Elsevier Inc. All rights reserved.

  7. Voxel-based lesion analysis of brain regions underlying reading and writing.

    Science.gov (United States)

    Baldo, Juliana V; Kacinik, Natalie; Ludy, Carl; Paulraj, Selvi; Moncrief, Amber; Piai, Vitória; Curran, Brian; Turken, And; Herron, Tim; Dronkers, Nina F

    2018-03-20

    The neural basis of reading and writing has been a source of inquiry as well as controversy in the neuroscience literature. Reading has been associated with both left posterior ventral temporal zones (termed the "visual word form area") as well as more dorsal zones, primarily in left parietal cortex. Writing has also been associated with left parietal cortex, as well as left sensorimotor cortex and prefrontal regions. Typically, the neural basis of reading and writing are examined in separate studies and/or rely on single case studies exhibiting specific deficits. Functional neuroimaging studies of reading and writing typically identify a large number of activated regions but do not necessarily identify the core, critical hubs. Last, due to constraints on the functional imaging environment, many previous studies have been limited to measuring the brain activity associated with single-word reading and writing, rather than sentence-level processing. In the current study, the brain correlates of reading and writing at both the single- and sentence-level were studied in a large sample of 111 individuals with a history of chronic stroke using voxel-based lesion symptom mapping (VLSM). VLSM provides a whole-brain, voxel-by-voxel statistical analysis of the role of distinct regions in a particular behavior by comparing performance of individuals with and without a lesion at every voxel. Rather than comparing individual cases or small groups with particular behavioral dissociations in reading and writing, VLSM allowed us to analyze data from a large, well-characterized sample of stroke patients exhibiting a wide range of reading and writing impairments. The VLSM analyses revealed that reading was associated with a critical left inferior temporo-occipital focus, while writing was primarily associated with the left supramarginal gyrus. Separate VLSM analyses of single-word versus sentence-level reading showed that sentence-level reading was uniquely associated with anterior

  8. Support vector machine classification and characterization of age-related reorganization of functional brain networks.

    Science.gov (United States)

    Meier, Timothy B; Desphande, Alok S; Vergun, Svyatoslav; Nair, Veena A; Song, Jie; Biswal, Bharat B; Meyerand, Mary E; Birn, Rasmus M; Prabhakaran, Vivek

    2012-03-01

    Most of what is known about the reorganization of functional brain networks that accompanies normal aging is based on neuroimaging studies in which participants perform specific tasks. In these studies, reorganization is defined by the differences in task activation between young and old adults. However, task activation differences could be the result of differences in task performance, strategy, or motivation, and not necessarily reflect reorganization. Resting-state fMRI provides a method of investigating functional brain networks without such confounds. Here, a support vector machine (SVM) classifier was used in an attempt to differentiate older adults from younger adults based on their resting-state functional connectivity. In addition, the information used by the SVM was investigated to see what functional connections best differentiated younger adult brains from older adult brains. Three separate resting-state scans from 26 younger adults (18-35 yrs) and 26 older adults (55-85) were obtained from the International Consortium for Brain Mapping (ICBM) dataset made publically available in the 1000 Functional Connectomes project www.nitrc.org/projects/fcon_1000. 100 seed-regions from four functional networks with 5mm(3) radius were defined based on a recent study using machine learning classifiers on adolescent brains. Time-series for every seed-region were averaged and three matrices of z-transformed correlation coefficients were created for each subject corresponding to each individual's three resting-state scans. SVM was then applied using leave-one-out cross-validation. The SVM classifier was 84% accurate in classifying older and younger adult brains. The majority of the connections used by the classifier to distinguish subjects by age came from seed-regions belonging to the sensorimotor and cingulo-opercular networks. These results suggest that age-related decreases in positive correlations within the cingulo-opercular and default networks, and decreases in

  9. Stability of whole brain and regional network topology within and between resting and cognitive states.

    Directory of Open Access Journals (Sweden)

    Justyna K Rzucidlo

    Full Text Available BACKGROUND: Graph-theory based analyses of resting state functional Magnetic Resonance Imaging (fMRI data have been used to map the network organization of the brain. While numerous analyses of resting state brain organization exist, many questions remain unexplored. The present study examines the stability of findings based on this approach over repeated resting state and working memory state sessions within the same individuals. This allows assessment of stability of network topology within the same state for both rest and working memory, and between rest and working memory as well. METHODOLOGY/PRINCIPAL FINDINGS: fMRI scans were performed on five participants while at rest and while performing the 2-back working memory task five times each, with task state alternating while they were in the scanner. Voxel-based whole brain network analyses were performed on the resulting data along with analyses of functional connectivity in regions associated with resting state and working memory. Network topology was fairly stable across repeated sessions of the same task, but varied significantly between rest and working memory. In the whole brain analysis, local efficiency, Eloc, differed significantly between rest and working memory. Analyses of network statistics for the precuneus and dorsolateral prefrontal cortex revealed significant differences in degree as a function of task state for both regions and in local efficiency for the precuneus. Conversely, no significant differences were observed across repeated sessions of the same state. CONCLUSIONS/SIGNIFICANCE: These findings suggest that network topology is fairly stable within individuals across time for the same state, but also fluid between states. Whole brain voxel-based network analyses may prove to be a valuable tool for exploring how functional connectivity changes in response to task demands.

  10. Brain region-specific perfluoroalkylated sulfonate (PFSA) and carboxylic acid (PFCA) accumulation and neurochemical biomarker responses in east Greenland polar bears (Ursus maritimus).

    Science.gov (United States)

    Eggers Pedersen, Kathrine; Basu, Niladri; Letcher, Robert; Greaves, Alana K; Sonne, Christian; Dietz, Rune; Styrishave, Bjarne

    2015-04-01

    Perfluoroalkyl substances (PFASs) is a growing class of contaminants in the Arctic environment, and include the established perfluorinated sulfonates (PFSAs; especially perfluorooctane sulfonate (PFOS)) and carboxylic acids (PFCAs). PFSAs and PFCAs of varying chain length have been reported to bioaccumulate in lipid rich tissues of the brain among other tissues such as liver, and can reach high concentrations in top predators including the polar bear. PFCA and PFSA bioaccummulation in the brain has the potential to pose neurotoxic effects and therefore we conducted a study to investigate if variations in neurochemical transmitter systems i.e. the cholinergic, glutaminergic, dopaminergic and GABAergic, could be related to brain-specific bioaccumulation of PFASs in East Greenland polar bears. Nine brain regions from nine polar bears were analyzed for enzyme activity (monoamine oxidase (MAO), acetylcholinesterase (AChE) and glutamine synthetase (GS)) and receptor density (dopamine-2 (D2), muscarinic cholinergic (mAChR) and gamma-butyric acid type A (GABA-A)) along with PFSA and PFCA concentrations. Average brain ∑PFSA concentration was 25ng/g ww where PFOS accounted for 91%. Average ∑PFCA concentration was 88ng/g ww where PFUnDA, PFDoDA and PFTrDA combined accounted for 79%. The highest concentrations of PFASs were measured in brain stem, cerebellum and hippocampus. Correlative analyses were performed both across and within brain regions. Significant positive correlations were found between PFASs and MAO activity in occipital lobe (e.g. ∑PFCA; rp=0.83, p=0.041, n=6) and across brain regions (e.g. ∑PFCA; rp=0.47, p=0.001, ∑PFSA; rp=0.44, p>0.001; n=50). GABA-A receptor density was positively correlated with two PFASs across brain regions (PFOS; rp=0.33, p=0.02 and PFDoDA; rp=0.34, p=0.014; n=52). Significant negative correlations were found between mAChR density and PFASs in cerebellum (e.g. ∑PFCA; rp=-0.95, p=0.013, n=5) and across brain regions (e.g.

  11. Brain alpha-ketoglutarate dehydrogenase complex: kinetic properties, regional distribution, and effects of inhibitors.

    Science.gov (United States)

    Lai, J C; Cooper, A J

    1986-11-01

    The substrate and cofactor requirements and some kinetic properties of the alpha-ketoglutarate dehydrogenase complex (KGDHC; EC 1.2.4.2, EC 2.3.1.61, and EC 1.6.4.3) in purified rat brain mitochondria were studied. Brain mitochondrial KGDHC showed absolute requirement for alpha-ketoglutarate, CoA and NAD, and only partial requirement for added thiamine pyrophosphate, but no requirement for Mg2+ under the assay conditions employed in this study. The pH optimum was between 7.2 and 7.4, but, at pH values below 7.0 or above 7.8, KGDHC activity decreased markedly. KGDHC activity in various brain regions followed the rank order: cerebral cortex greater than cerebellum greater than or equal to midbrain greater than striatum = hippocampus greater than hypothalamus greater than pons and medulla greater than olfactory bulb. Significant inhibition of brain mitochondrial KGDHC was noted at pathological concentrations of ammonia (0.2-2 mM). However, the purified bovine heart KGDHC and KGDHC activity in isolated rat heart mitochondria were much less sensitive to inhibition. At 5 mM both beta-methylene-D,L-aspartate and D,L-vinylglycine (inhibitors of cerebral glucose oxidation) inhibited the purified heart but not the brain mitochondrial enzyme complex. At approximately 10 microM, calcium slightly stimulated (by 10-15%) the brain mitochondrial KGDHC. At concentrations above 100 microM, calcium (IC50 = 1 mM) inhibited both brain mitochondrial and purified heart KGDHC. The present results suggest that some of the kinetic properties of the rat brain mitochondrial KGDHC differ from those of the purified bovine heart and rat heart mitochondrial enzyme complexes. They also suggest that the inhibition of KGDHC by ammonia and the consequent effect on the citric acid cycle fluxes may be of pathophysiological and/or pathogenetic importance in hyperammonemia and in diseases (e.g., hepatic encephalopathy, inborn errors of urea metabolism, Reye's syndrome) where hyperammonemia is a

  12. Simplified methods for in vivo measurement of acetylcholinesterase activity in rodent brain

    International Nuclear Information System (INIS)

    Kilbourn, Michael R.; Sherman, Phillip S.; Snyder, Scott E.

    1999-01-01

    Simplified methods for in vivo studies of acetylcholinesterase (AChE) activity in rodent brain were evaluated using N-[ 11 C]methylpiperidinyl propionate ([ 11 C]PMP) as an enzyme substrate. Regional mouse brain distributions were determined at 1 min (representing initial brain uptake) and 30 min (representing trapped product) after intravenous [ 11 C]PMP administration. Single time point tissue concentrations (percent injected dose/gram at 30 min), tissue concentration ratios (striatum/cerebellum and striatum/cortex ratios at 30 min), and regional tissue retention fractions (defined as percent injected dose 30 min/percent injected dose 1 min) were evaluated as measures of AChE enzymatic activity in mouse brain. Studies were carried out in control animals and after dosing with phenserine, a selective centrally active AChE inhibitor; neostigmine, a peripheral cholinesterase inhibitor; and a combination of the two drugs. In control and phenserine-treated animals, absolute tissue concentrations and regional retention fractions provide good measures of dose-dependent inhibition of brain AChE; tissue concentration ratios, however, provide erroneous conclusions. Peripheral inhibition of cholinesterases, which changes the blood pharmacokinetics of the radiotracer, diminishes the sensitivity of all measures to detect changes in central inhibition of the enzyme. We conclude that certain simple measures of AChE hydrolysis rates for [ 11 C]PMP are suitable for studies where alterations of the peripheral blood metabolism of the tracer are kept to a minimum

  13. The epsins define a family of proteins that interact with components of the clathrin coat and contain a new protein module

    DEFF Research Database (Denmark)

    Rosenthal, J A; Chen, H; Slepnev, V I

    1999-01-01

    Epsin (epsin 1) is an interacting partner for the EH domain-containing region of Eps15 and has been implicated in conjunction with Eps15 in clathrin-mediated endocytosis. We report here the characterization of a similar protein (epsin 2), which we have cloned from human and rat brain libraries. E...... fluorescent protein-epsin 2 mislocalizes components of the clathrin coat and inhibits clathrin-mediated endocytosis. The epsins define a new protein family implicated in membrane dynamics at the cell surface.......Epsin (epsin 1) is an interacting partner for the EH domain-containing region of Eps15 and has been implicated in conjunction with Eps15 in clathrin-mediated endocytosis. We report here the characterization of a similar protein (epsin 2), which we have cloned from human and rat brain libraries...

  14. Mean transit time image - a new method of analyzing brain perfusion studies

    Energy Technology Data Exchange (ETDEWEB)

    Szabo, Z.; Ritzl, F.

    1983-05-01

    Point-by-point calculation of the mean transit time based on gamma fit was used to analyze brain perfusion studies in a vertex view. The algorithm and preliminary results in normal brain and in different stages of cerebral perfusion abnormality (ischemia, stroke, migraine, tumor, abscess) are demonstrated. In contrast to the traditional methods using fixed, a priori defined regions of interest this type of mapping of the relative regions cerebral perfusion shows more clearly the irregular outlines of the disturbance. Right to left activity ratios in the arterial part of the time-activity curves showed significant correlation with the mean transit time ratios (Q/sub 1/=1.185-0.192 Qsub(a), n=38, r=0.716, P<0.001).

  15. Synaptic Tau Seeding Precedes Tau Pathology in Human Alzheimer's Disease Brain

    Directory of Open Access Journals (Sweden)

    Sarah L. DeVos

    2018-04-01

    Full Text Available Alzheimer's disease (AD is defined by the presence of intraneuronal neurofibrillary tangles (NFTs composed of hyperphosphorylated tau aggregates as well as extracellular amyloid-beta plaques. The presence and spread of tau pathology through the brain is classified by Braak stages and thought to correlate with the progression of AD. Several in vitro and in vivo studies have examined the ability of tau pathology to move from one neuron to the next, suggesting a “prion-like” spread of tau aggregates may be an underlying cause of Braak tau staging in AD. Using the HEK293 TauRD-P301S-CFP/YFP expressing biosensor cells as a highly sensitive and specific tool to identify the presence of seed competent aggregated tau in brain lysate—i.e., tau aggregates that are capable of recruiting and misfolding monomeric tau—, we detected substantial tau seeding levels in the entorhinal cortex from human cases with only very rare NFTs, suggesting that soluble tau aggregates can exist prior to the development of overt tau pathology. We next looked at tau seeding levels in human brains of varying Braak stages along six regions of the Braak Tau Pathway. Tau seeding levels were detected not only in the brain regions impacted by pathology, but also in the subsequent non-pathology containing region along the Braak pathway. These data imply that pathogenic tau aggregates precede overt tau pathology in a manner that is consistent with transneuronal spread of tau aggregates. We then detected tau seeding in frontal white matter tracts and the optic nerve, two brain regions comprised of axons that contain little to no neuronal cell bodies, implying that tau aggregates can indeed traverse along axons. Finally, we isolated cytosolic and synaptosome fractions along the Braak Tau Pathway from brains of varying Braak stages. Phosphorylated and seed competent tau was significantly enriched in the synaptic fraction of brain regions that did not have extensive cellular tau

  16. Recruitment of Language-, Emotion- and Speech-Timing Associated Brain Regions for Expressing Emotional Prosody: Investigation of Functional Neuroanatomy with fMRI.

    Science.gov (United States)

    Mitchell, Rachel L C; Jazdzyk, Agnieszka; Stets, Manuela; Kotz, Sonja A

    2016-01-01

    We aimed to progress understanding of prosodic emotion expression by establishing brain regions active when expressing specific emotions, those activated irrespective of the target emotion, and those whose activation intensity varied depending on individual performance. BOLD contrast data were acquired whilst participants spoke non-sense words in happy, angry or neutral tones, or performed jaw-movements. Emotion-specific analyses demonstrated that when expressing angry prosody, activated brain regions included the inferior frontal and superior temporal gyri, the insula, and the basal ganglia. When expressing happy prosody, the activated brain regions also included the superior temporal gyrus, insula, and basal ganglia, with additional activation in the anterior cingulate. Conjunction analysis confirmed that the superior temporal gyrus and basal ganglia were activated regardless of the specific emotion concerned. Nevertheless, disjunctive comparisons between the expression of angry and happy prosody established that anterior cingulate activity was significantly higher for angry prosody than for happy prosody production. Degree of inferior frontal gyrus activity correlated with the ability to express the target emotion through prosody. We conclude that expressing prosodic emotions (vs. neutral intonation) requires generic brain regions involved in comprehending numerous aspects of language, emotion-related processes such as experiencing emotions, and in the time-critical integration of speech information.

  17. Recruitment of language-, emotion- and speech timing associated brain regions for expressing emotional prosody: Investigation of functional neuroanatomy with fMRI.

    Directory of Open Access Journals (Sweden)

    Rachel L. C. Mitchell

    2016-10-01

    Full Text Available We aimed to progress understanding of prosodic emotion expression by establishing brain regions active when expressing specific emotions, those activated irrespective of the target emotion, and those whose activation intensity varied depending on individual performance. BOLD contrast data were acquired whilst participants spoke nonsense words in happy, angry or neutral tones, or performed jaw-movements. Emotion-specific analyses demonstrated that when expressing angry prosody, activated brain regions included the inferior frontal and superior temporal gyri, the insula, and the basal ganglia. When expressing happy prosody, the activated brain regions also included the superior temporal gyrus, insula, and basal ganglia, with additional activation in the anterior cingulate. Conjunction analysis confirmed that the superior temporal gyrus and basal ganglia were activated regardless of the specific emotion concerned. Nevertheless, disjunctive comparisons between the expression of angry and happy prosody established that anterior cingulate activity was significantly higher for angry prosody than for happy prosody production. Degree of inferior frontal gyrus activity correlated with the ability to express the target emotion through prosody. We conclude that expressing prosodic emotions (vs neutral intonation requires generic brain regions involved in comprehending numerous aspects of language, emotion-related processes such as experiencing emotions, and in the time-critical integration of speech information.

  18. Protective role of Cynodon dactylon in ameliorating the aluminium-induced neurotoxicity in rat brain regions.

    Science.gov (United States)

    Sumathi, Thangarajan; Shobana, Chandrasekar; Kumari, Balasubramanian Rathina; Nandhini, Devarajulu Nisha

    2011-12-01

    Cynodon dactylon (Poaceae) is a creeping grass used as a traditional ayurvedic medicine in India. Aluminium-induced neurotoxicity is well known and different salts of aluminium have been reported to accelerate damage to biomolecules like lipids, proteins and nucleic acids. The objective of the present study was to investigate whether the aqueous extract of C. dactylon (AECD) could potentially prevent aluminium-induced neurotoxicity in the cerebral cortex, hippocampus and cerebellum of the rat brain. Male albino rats were administered with AlCl(3) at a dose of 4.2 mg/kg/day i.p. for 4 weeks. Experimental rats were given C. dactylon extract in two different doses of 300 mg and 750 mg/keg/day orally 1 h prior to the AlCl(3) administration for 4 weeks. At the end of the experiments, antioxidant status and activities of ATPases in cerebral cortex, hippocampus and cerebellum of rat brain were measured. Aluminium administration significantly decreased the level of GSH and the activities of SOD, GPx, GST, Na(+)/K(+) ATPase, and Mg(2+) ATPase and increased the level of lipid peroxidation (LPO) in all the brain regions when compared with control rats. Pre-treatment with AECD at a dose of 750 mg/kg b.w increased the antioxidant status and activities of membrane-bound enzymes (Na(+)/K(+) ATPase and Mg(2+) ATPase) and also decreased the level of LPO significantly, when compared with aluminium-induced rats. The results of this study indicated that AECD has potential to protect the various brain regions from aluminium-induced neurotoxicity.

  19. Synapsin I (protein I) in different brain regions in senile dementia of Alzheimer type and in multiinfarct dementia

    International Nuclear Information System (INIS)

    Adolfsson, R.; Alafuzoff, I.; Winblad, B.; Perdahl, E.; Albert, K.A.; Nestler, E.J.; Greengard, P.

    1984-01-01

    Synapsin I (Protein I), a neuron-specfic phosphoprotein enriched in presynaptic nerve terminals, has been used as a quantitative marker for the density of nerve terminals in five brain regions (caudate nucleus, cingulate gyrus, hippocampus, mesencephalon and putamen) from patients who had suffered from Alzheimer disease/senile dementia of Alzheimer type (AD/SDAT), from patients with multi-infarct dementia (MID), and from agematched controls. Samples were obtained at autopsy. Lower levels of Synapsin I were observed in the hippocampus of patients with AD/SDAT but not with MID. There were no significant differences in Synapsin I levels between patients and controls in any of the other four brain regions examined. (Author)

  20. Differential Recruitment of Brain Regions During Response Inhibition in Children Prenatally Exposed to Alcohol.

    Science.gov (United States)

    Kodali, Vikas N; Jacobson, Joseph L; Lindinger, Nadine M; Dodge, Neil C; Molteno, Christopher D; Meintjes, Ernesta M; Jacobson, Sandra W

    2017-02-01

    Response inhibition is a distinct aspect of executive function that is frequently impaired in children with fetal alcohol spectrum disorders (FASD). We used a Go/NoGo (GNG) task in a functional MRI protocol to investigate differential activation of brain regions in the response inhibition network in children diagnosed with full or partial fetal alcohol syndrome (FAS/PFAS), compared with healthy controls. A rapid, event-related task with 120 Go and 60 NoGo trials was used to study children aged 8 to 12 years-8 with FAS/PFAS, 17 controls. Letters were projected sequentially, with Go and NoGo trials randomly interspersed across the task. BOLD signal in the whole brain was contrasted for the correct NoGo minus correct Go trials between the FAS/PFAS and control groups. Compared to the FAS/PFAS group, controls showed greater activation of the inferior frontal and anterior cingulate network linked to response inhibition in typically developing children. By contrast, the FAS/PFAS group showed greater BOLD response in dorsolateral prefrontal cortex and other middle prefrontal regions, suggesting compensation for inefficient function of pathways that normally mediate inhibitory processing. All group differences were significant after control for potential confounding variables. None of the effects of prenatal alcohol exposure on activation of the regions associated with response inhibition were attributable to the effects of this exposure on IQ. This is the first FASD GNG study in which all participants in the exposed group met criteria for a diagnosis of full FAS or PFAS. Although FASD is frequently comorbid with attention deficit hyperactivity disorder, the pattern of brain activation seen in these disorders differs, suggesting that different neural pathways mediate response inhibition in FASD and that different interventions for FASD are, therefore, warranted. Copyright © 2017 by the Research Society on Alcoholism.

  1. Defining the Construct of Synthetic Androgen Intoxication: An Application of General Brain Arousal.

    Science.gov (United States)

    Hildebrandt, Tom; Heywood, Ashley; Wesley, Daniel; Schulz, Kurt

    2018-01-01

    Synthetic androgens (i. e., anabolic-androgenic steroids) are the primary component to the majority of problematic appearance and performance enhancing drug (APED) use. Despite evidence that these substances are associated with increased risk for aggression, violence, body image disturbances, and polypharmacy and can develop a pattern of chronic use consistent with drug dependence, there are no formal definitions of androgen intoxication. Consequently, the purpose of this paper is to establish a testable theory of androgen intoxication. We present evidence and theorize that synthetic androgen intoxication can be defined by a pattern of poor self-regulation characterized by increased propensity for a range of behaviors (e.g., aggression, sex, drug seeking, exercise, etc.) via androgen mediated effects on general brain arousal. This theory posits that androgens reduce threshold for emotional reactivity, motor response, and alertness to sensory stimuli and disrupt inhibitory control over the behaviors associated with synthetic androgen use. These changes result from alteration to basic neurocircuitry that amplifies limbic activation and reduces top-down cortical control. The implications for this definition are to inform APED specific hypotheses about the behavioral and psychological effects of APED use and provide a basis for establishing clinical, legal, and public health guidelines to address the use and misuse of these substances.

  2. Defining the Construct of Synthetic Androgen Intoxication: An Application of General Brain Arousal

    Directory of Open Access Journals (Sweden)

    Tom Hildebrandt

    2018-03-01

    Full Text Available Synthetic androgens (i. e., anabolic-androgenic steroids are the primary component to the majority of problematic appearance and performance enhancing drug (APED use. Despite evidence that these substances are associated with increased risk for aggression, violence, body image disturbances, and polypharmacy and can develop a pattern of chronic use consistent with drug dependence, there are no formal definitions of androgen intoxication. Consequently, the purpose of this paper is to establish a testable theory of androgen intoxication. We present evidence and theorize that synthetic androgen intoxication can be defined by a pattern of poor self-regulation characterized by increased propensity for a range of behaviors (e.g., aggression, sex, drug seeking, exercise, etc. via androgen mediated effects on general brain arousal. This theory posits that androgens reduce threshold for emotional reactivity, motor response, and alertness to sensory stimuli and disrupt inhibitory control over the behaviors associated with synthetic androgen use. These changes result from alteration to basic neurocircuitry that amplifies limbic activation and reduces top-down cortical control. The implications for this definition are to inform APED specific hypotheses about the behavioral and psychological effects of APED use and provide a basis for establishing clinical, legal, and public health guidelines to address the use and misuse of these substances.

  3. A map of octopaminergic neurons in the Drosophila brain.

    Science.gov (United States)

    Busch, Sebastian; Selcho, Mareike; Ito, Kei; Tanimoto, Hiromu

    2009-04-20

    The biogenic amine octopamine modulates diverse behaviors in invertebrates. At the single neuron level, the mode of action is well understood in the peripheral nervous system owing to its simple structure and accessibility. For elucidating the role of individual octopaminergic neurons in the modulation of complex behaviors, a detailed analysis of the connectivity in the central nervous system is required. Here we present a comprehensive anatomical map of candidate octopaminergic neurons in the adult Drosophila brain: including the supra- and subesophageal ganglia. Application of the Flp-out technique enabled visualization of 27 types of individual octopaminergic neurons. Based on their morphology and distribution of genetic markers, we found that most octopaminergic neurons project to multiple brain structures with a clear separation of dendritic and presynaptic regions. Whereas their major dendrites are confined to specific brain regions, each cell type targets different, yet defined, neuropils distributed throughout the central nervous system. This would allow them to constitute combinatorial modules assigned to the modulation of distinct neuronal processes. The map may provide an anatomical framework for the functional constitution of the octopaminergic system. It also serves as a model for the single-cell organization of a particular neurotransmitter in the brain. 2009 Wiley-Liss, Inc.

  4. RNA-Seq Mouse Brain Regions Expression Data Analysis: Focus on ApoE Functional Network

    Directory of Open Access Journals (Sweden)

    Babenko Vladimir N.

    2017-09-01

    Full Text Available ApoE expression status was proved to be a highly specific marker of energy metabolism rate in the brain. Along with its neighbor, Translocase of Outer Mitochondrial Membrane 40 kDa (TOMM40 which is involved in mitochondrial metabolism, the corresponding genomic region constitutes the neuroenergetic hotspot. Using RNA-Seq data from a murine model of chronic stress a significant positive expression coordination of seven neighboring genes in ApoE locus in five brain regions was observed. ApoE maintains one of the highest absolute expression values genome-wide, implying that ApoE can be the driver of the neighboring gene expression alteration observed under stressful loads. Notably, we revealed the highly statistically significant increase of ApoE expression in the hypothalamus of chronically aggressive (FDR < 0.007 and defeated (FDR < 0.001 mice compared to the control. Correlation analysis revealed a close association of ApoE and proopiomelanocortin (Pomc gene expression profiles implying the putative neuroendocrine stress response background of ApoE expression elevation therein.

  5. The SRCR/SID region of DMBT1 defines a complex multi-allele system representing the major basis for its variability in cancer

    DEFF Research Database (Denmark)

    Mollenhauer, Jan; Müller, Hanna; Kollender, Gaby

    2002-01-01

    Deleted in malignant brain tumors 1 (DMBT1) at 10q25.3-q26.1 has been proposed as a candidate tumor-suppressor gene for brain and epithelial cancer. DMBT1 encodes a multifunctional mucin-like protein presumably involved in epithelial differentiation and protection. The gene consists of highly...... homologous and repeating exon and intron sequences. This specifically applies to the region coding for the repetitive scavenger receptor cysteine-rich (SRCR) domains and SRCR-interspersed domains (SIDs) that constitutes the major part of the gene. This particular structure may previously have interfered...... with the delineation of DMBT1 alterations in cancer. Uncovering these, however, is of mechanistic importance. By a combined approach, we conducted a detailed mutational analysis, starting from a panel of 51 tumors, including 46 tumor cell lines and five primary tumors. Alterations in the repetitive region were present...

  6. Network Theory and Effects of Transcranial Brain Stimulation Methods on the Brain Networks

    Directory of Open Access Journals (Sweden)

    Sema Demirci

    2014-12-01

    Full Text Available In recent years, there has been a shift from classic localizational approaches to new approaches where the brain is considered as a complex system. Therefore, there has been an increase in the number of studies involving collaborations with other areas of neurology in order to develop methods to understand the complex systems. One of the new approaches is graphic theory that has principles based on mathematics and physics. According to this theory, the functional-anatomical connections of the brain are defined as a network. Moreover, transcranial brain stimulation techniques are amongst the recent research and treatment methods that have been commonly used in recent years. Changes that occur as a result of applying brain stimulation techniques on physiological and pathological networks help better understand the normal and abnormal functions of the brain, especially when combined with techniques such as neuroimaging and electroencephalography. This review aims to provide an overview of the applications of graphic theory and related parameters, studies conducted on brain functions in neurology and neuroscience, and applications of brain stimulation systems in the changing treatment of brain network models and treatment of pathological networks defined on the basis of this theory.

  7. Genome-wide DNA methylation analyses in the brain reveal four differentially methylated regions between humans and non-human primates

    Directory of Open Access Journals (Sweden)

    Wang Jinkai

    2012-08-01

    Full Text Available Abstract Background The highly improved cognitive function is the most significant change in human evolutionary history. Recently, several large-scale studies reported the evolutionary roles of DNA methylation; however, the role of DNA methylation on brain evolution is largely unknown. Results To test if DNA methylation has contributed to the evolution of human brain, with the use of MeDIP-Chip and SEQUENOM MassARRAY, we conducted a genome-wide analysis to identify differentially methylated regions (DMRs in the brain between humans and rhesus macaques. We first identified a total of 150 candidate DMRs by the MeDIP-Chip method, among which 4 DMRs were confirmed by the MassARRAY analysis. All 4 DMRs are within or close to the CpG islands, and a MIR3 repeat element was identified in one DMR, but no repeat sequence was observed in the other 3 DMRs. For the 4 DMR genes, their proteins tend to be conserved and two genes have neural related functions. Bisulfite sequencing and phylogenetic comparison among human, chimpanzee, rhesus macaque and rat suggested several regions of lineage specific DNA methylation, including a human specific hypomethylated region in the promoter of K6IRS2 gene. Conclusions Our study provides a new angle of studying human brain evolution and understanding the evolutionary role of DNA methylation in the central nervous system. The results suggest that the patterns of DNA methylation in the brain are in general similar between humans and non-human primates, and only a few DMRs were identified.

  8. Mapping and characterization of positive and negative BOLD responses to visual stimulation in multiple brain regions at 7T.

    Science.gov (United States)

    Jorge, João; Figueiredo, Patrícia; Gruetter, Rolf; van der Zwaag, Wietske

    2018-02-20

    External stimuli and tasks often elicit negative BOLD responses in various brain regions, and growing experimental evidence supports that these phenomena are functionally meaningful. In this work, the high sensitivity available at 7T was explored to map and characterize both positive (PBRs) and negative BOLD responses (NBRs) to visual checkerboard stimulation, occurring in various brain regions within and beyond the visual cortex. Recently-proposed accelerated fMRI techniques were employed for data acquisition, and procedures for exclusion of large draining vein contributions, together with ICA-assisted denoising, were included in the analysis to improve response estimation. Besides the visual cortex, significant PBRs were found in the lateral geniculate nucleus and superior colliculus, as well as the pre-central sulcus; in these regions, response durations increased monotonically with stimulus duration, in tight covariation with the visual PBR duration. Significant NBRs were found in the visual cortex, auditory cortex, default-mode network (DMN) and superior parietal lobule; NBR durations also tended to increase with stimulus duration, but were significantly less sustained than the visual PBR, especially for the DMN and superior parietal lobule. Responses in visual and auditory cortex were further studied for checkerboard contrast dependence, and their amplitudes were found to increase monotonically with contrast, linearly correlated with the visual PBR amplitude. Overall, these findings suggest the presence of dynamic neuronal interactions across multiple brain regions, sensitive to stimulus intensity and duration, and demonstrate the richness of information obtainable when jointly mapping positive and negative BOLD responses at a whole-brain scale, with ultra-high field fMRI. © 2018 Wiley Periodicals, Inc.

  9. Opiate antagonist binding sites in discrete brain regions of spontaneously hypertensive and normotensive Wistar-Kyoto rats

    Energy Technology Data Exchange (ETDEWEB)

    Rahmani, N.H.; Gulati, A.; Bhargava, H.N. (Univ. of Illinois, Chicago (USA))

    1991-01-01

    The binding of {sup 3}H-naltrexone, an opiate receptor antagonist, to membranes of discrete brain regions and spinal cord of 10 week old spontaneously hypertensive (SHR) and normotensive Wistar-Kyoto (WKY) rats was determined. The brain regions examined were hypothalamus, amygdala, hippocampus, corpus striatum, pons and medulla, midbrain and cortex. {sup 3}H-Naltrexone bound to membranes of brain regions and spinal cord at a single high affinity site with an apparent dissociation constant value of 3 nM. The highest density of {sup 3}H-naltrexone binding sites were in hippocampus and lowest in the cerebral cortex. The receptor density (B{sub max}value) and apparent dissociation constant (K{sub d} value) values of {sup 3}H-naltrexone to bind to opiate receptors on the membranes of amygdala, hippocampus, corpus striatum, pons and medulla, midgrain, cortex and spinal cord of WKY and SHR rates did not differ. The B{sub max} value of {sup 3}H-naltrexone binding to membranes of hypothalamus of SHR rates was 518% higher than WKY rats but the K{sub d} values in the two strains did not differ. It is concluded that SHR rats have higher density of opiate receptors labeled with {sup 3}H-naltrexone in the hypothalamus only, in comparison with WKY rats, and that such a difference in the density of opiate receptors may be related to the elevated blood pressure in SHR rats.

  10. View-Independent Working Memory Representations of Artificial Shapes in Prefrontal and Posterior Regions of the Human Brain.

    Science.gov (United States)

    Christophel, Thomas B; Allefeld, Carsten; Endisch, Christian; Haynes, John-Dylan

    2017-05-13

    Traditional views of visual working memory postulate that memorized contents are stored in dorsolateral prefrontal cortex using an adaptive and flexible code. In contrast, recent studies proposed that contents are maintained by posterior brain areas using codes akin to perceptual representations. An important question is whether this reflects a difference in the level of abstraction between posterior and prefrontal representations. Here, we investigated whether neural representations of visual working memory contents are view-independent, as indicated by rotation-invariance. Using functional magnetic resonance imaging and multivariate pattern analyses, we show that when subjects memorize complex shapes, both posterior and frontal brain regions maintain the memorized contents using a rotation-invariant code. Importantly, we found the representations in frontal cortex to be localized to the frontal eye fields rather than dorsolateral prefrontal cortices. Thus, our results give evidence for the view-independent storage of complex shapes in distributed representations across posterior and frontal brain regions. © The Author 2017. Published by Oxford University Press. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.

  11. Early cellular responses against tributyltin chloride exposure in primary cultures derived from various brain regions.

    Science.gov (United States)

    Mitra, Sumonto; Siddiqui, Waseem A; Khandelwal, Shashi

    2014-05-01

    Tributyltin (TBT) is a potent biocide and commonly used in various industrial sectors. Humans are mainly exposed through the food chain. We have previously demonstrated tin accumulation in brain following TBT-chloride (TBTC) exposure. In this study, effect of TBTC on dissociated cells from different brain regions was evaluated. Cytotoxicity assay (MTT), mode of cell death (Annexin V/PI assay), oxidative stress parameters (ROS and lipid peroxidation), reducing power of the cell (GSH), mitochondrial membrane potential (MMP) and intracellular Ca(2+) were evaluated to ascertain the effect of TBTC. Expression of glial fibrillary acidic protein (GFAP) was measured to understand the effect on astroglial cells. TBTC as low as 30 nM was found to reduce GSH levels, whereas higher doses of 300 and 3000 nM induced ROS generation and marked loss in cell viability mainly through apoptosis. Striatum showed higher susceptibility than other regions, which may have further implications on various neurological aspects. Copyright © 2014 Elsevier B.V. All rights reserved.

  12. Magnetic Resonance Imaging-Based Target Volume Delineation in Radiation Therapy Treatment Planning for Brain Tumors Using Localized Region-Based Active Contour

    International Nuclear Information System (INIS)

    Aslian, Hossein; Sadeghi, Mahdi; Mahdavi, Seied Rabie; Babapour Mofrad, Farshid; Astarakee, Mahdi; Khaledi, Navid; Fadavi, Pedram

    2013-01-01

    Purpose: To evaluate the clinical application of a robust semiautomatic image segmentation method to determine the brain target volumes in radiation therapy treatment planning. Methods and Materials: A local robust region-based algorithm was used on MRI brain images to study the clinical target volume (CTV) of several patients. First, 3 oncologists delineated CTVs of 10 patients manually, and the process time for each patient was calculated. The averages of the oncologists’ contours were evaluated and considered as reference contours. Then, to determine the CTV through the semiautomatic method, a fourth oncologist who was blind to all manual contours selected 4-8 points around the edema and defined the initial contour. The time to obtain the final contour was calculated again for each patient. Manual and semiautomatic segmentation were compared using 3 different metric criteria: Dice coefficient, Hausdorff distance, and mean absolute distance. A comparison also was performed between volumes obtained from semiautomatic and manual methods. Results: Manual delineation processing time of tumors for each patient was dependent on its size and complexity and had a mean (±SD) of 12.33 ± 2.47 minutes, whereas it was 3.254 ± 1.7507 minutes for the semiautomatic method. Means of Dice coefficient, Hausdorff distance, and mean absolute distance between manual contours were 0.84 ± 0.02, 2.05 ± 0.66 cm, and 0.78 ± 0.15 cm, and they were 0.82 ± 0.03, 1.91 ± 0.65 cm, and 0.7 ± 0.22 cm between manual and semiautomatic contours, respectively. Moreover, the mean volume ratio (=semiautomatic/manual) calculated for all samples was 0.87. Conclusions: Given the deformability of this method, the results showed reasonable accuracy and similarity to the results of manual contouring by the oncologists. This study shows that the localized region-based algorithms can have great ability in determining the CTV and can be appropriate alternatives for manual approaches in brain cancer

  13. Magnetic Resonance Imaging-Based Target Volume Delineation in Radiation Therapy Treatment Planning for Brain Tumors Using Localized Region-Based Active Contour

    Energy Technology Data Exchange (ETDEWEB)

    Aslian, Hossein [Department of Medical Radiation, Science and Research Branch, Islamic Azad University, Tehran (Iran, Islamic Republic of); Sadeghi, Mahdi [Agricultural, Medical and Industrial Research School, Karaj (Iran, Islamic Republic of); Mahdavi, Seied Rabie [Department of Medical Physics, Iran University of Medical Sciences, Tehran (Iran, Islamic Republic of); Babapour Mofrad, Farshid [Department of Medical Radiation, Science and Research Branch, Islamic Azad University, Tehran (Iran, Islamic Republic of); Astarakee, Mahdi, E-mail: M-Astarakee@Engineer.com [Department of Biomedical Engineering, Science and Research Branch, Islamic Azad University, Tehran (Iran, Islamic Republic of); Khaledi, Navid [Department of Medical Radiation, Science and Research Branch, Islamic Azad University, Tehran (Iran, Islamic Republic of); Fadavi, Pedram [Department of Radiation Oncology, Iran University of Medical Sciences, Tehran (Iran, Islamic Republic of)

    2013-09-01

    Purpose: To evaluate the clinical application of a robust semiautomatic image segmentation method to determine the brain target volumes in radiation therapy treatment planning. Methods and Materials: A local robust region-based algorithm was used on MRI brain images to study the clinical target volume (CTV) of several patients. First, 3 oncologists delineated CTVs of 10 patients manually, and the process time for each patient was calculated. The averages of the oncologists’ contours were evaluated and considered as reference contours. Then, to determine the CTV through the semiautomatic method, a fourth oncologist who was blind to all manual contours selected 4-8 points around the edema and defined the initial contour. The time to obtain the final contour was calculated again for each patient. Manual and semiautomatic segmentation were compared using 3 different metric criteria: Dice coefficient, Hausdorff distance, and mean absolute distance. A comparison also was performed between volumes obtained from semiautomatic and manual methods. Results: Manual delineation processing time of tumors for each patient was dependent on its size and complexity and had a mean (±SD) of 12.33 ± 2.47 minutes, whereas it was 3.254 ± 1.7507 minutes for the semiautomatic method. Means of Dice coefficient, Hausdorff distance, and mean absolute distance between manual contours were 0.84 ± 0.02, 2.05 ± 0.66 cm, and 0.78 ± 0.15 cm, and they were 0.82 ± 0.03, 1.91 ± 0.65 cm, and 0.7 ± 0.22 cm between manual and semiautomatic contours, respectively. Moreover, the mean volume ratio (=semiautomatic/manual) calculated for all samples was 0.87. Conclusions: Given the deformability of this method, the results showed reasonable accuracy and similarity to the results of manual contouring by the oncologists. This study shows that the localized region-based algorithms can have great ability in determining the CTV and can be appropriate alternatives for manual approaches in brain cancer.

  14. Altered spontaneous brain activity in adolescent boys with pure conduct disorder revealed by regional homogeneity analysis.

    Science.gov (United States)

    Wu, Qiong; Zhang, Xiaocui; Dong, Daifeng; Wang, Xiang; Yao, Shuqiao

    2017-07-01

    Functional magnetic resonance imaging (fMRI) studies have revealed abnormal neural activity in several brain regions of adolescents with conduct disorder (CD) performing various tasks. However, little is known about the spontaneous neural activity in people with CD in a resting state. The aims of this study were to investigate CD-associated regional activity abnormalities and to explore the relationship between behavioral impulsivity and regional activity abnormalities. Resting-state fMRI (rs-fMRI) scans were administered to 28 adolescents with CD and 28 age-, gender-, and IQ-matched healthy controls (HCs). The rs-fMRI data were subjected to regional homogeneity (ReHo) analysis. ReHo can demonstrate the temporal synchrony of regional blood oxygen level-dependent signals and reflect the coordination of local neuronal activity facilitating similar goals or representations. Compared to HCs, the CD group showed increased ReHo bilaterally in the insula as well as decreased ReHo in the right inferior parietal lobule, right middle temporal gyrus and right fusiform gyrus, left anterior cerebellum anterior, and right posterior cerebellum. In the CD group, mean ReHo values in the left and the right insula correlated positively with Barratt Impulsivity Scale (BIS) total scores. The results suggest that CD is associated with abnormal intrinsic brain activity, mainly in the cerebellum and temporal-parietal-limbic cortices, regions that are related to emotional and cognitive processing. BIS scores in adolescents with CD may reflect severity of abnormal neuronal synchronization in the insula.

  15. Brain regions involved in subprocesses of small-space episodic object-location memory: a systematic review of lesion and functional neuroimaging studies.

    Science.gov (United States)

    Zimmermann, Kathrin; Eschen, Anne

    2017-04-01

    Object-location memory (OLM) enables us to keep track of the locations of objects in our environment. The neurocognitive model of OLM (Postma, A., Kessels, R. P. C., & Van Asselen, M. (2004). The neuropsychology of object-location memory. In G. L. Allen (Ed.), Human spatial memory: Remembering where (pp. 143-160). Mahwah, NJ: Lawrence Erlbaum, Postma, A., Kessels, R. P. C., & Van Asselen, M. (2008). How the brain remembers and forgets where things are: The neurocognition of object-location memory. Neuroscience & Biobehavioral Reviews, 32, 1339-1345. doi: 10.1016/j.neubiorev.2008.05.001 ) proposes that distinct brain regions are specialised for different subprocesses of OLM (object processing, location processing, and object-location binding; categorical and coordinate OLM; egocentric and allocentric OLM). It was based mainly on findings from lesion studies. However, recent episodic memory studies point to a contribution of additional or different brain regions to object and location processing within episodic OLM. To evaluate and update the neurocognitive model of OLM, we therefore conducted a systematic literature search for lesion as well as functional neuroimaging studies contrasting small-space episodic OLM with object memory or location memory. We identified 10 relevant lesion studies and 8 relevant functional neuroimaging studies. We could confirm some of the proposals of the neurocognitive model of OLM, but also differing hypotheses from episodic memory research, about which brain regions are involved in the different subprocesses of small-space episodic OLM. In addition, we were able to identify new brain regions as well as important research gaps.

  16. Exercise increases blood flow to locomotor, vestibular, cardiorespiratory and visual regions of the brain in miniature swine

    Science.gov (United States)

    Delp, M. D.; Armstrong, R. B.; Godfrey, D. A.; Laughlin, M. H.; Ross, C. D.; Wilkerson, M. K.

    2001-01-01

    1. The purpose of these experiments was to use radiolabelled microspheres to measure blood flow distribution within the brain, and in particular to areas associated with motor function, maintenance of equilibrium, cardiorespiratory control, vision, hearing and smell, at rest and during exercise in miniature swine. Exercise consisted of steady-state treadmill running at intensities eliciting 70 and 100 % maximal oxygen consumption (V(O(2),max)). 2. Mean arterial pressure was elevated by 17 and 26 % above that at rest during exercise at 70 and 100 % V(O(2),max), respectively. 3. Mean brain blood flow increased 24 and 25 % at 70 and 100 % V(O(2),max), respectively. Blood flow was not locally elevated to cortical regions associated with motor and somatosensory functions during exercise, but was increased to several subcortical areas that are involved in the control of locomotion. 4. Exercise elevated perfusion and diminished vascular resistance in several regions of the brain related to the maintenance of equilibrium (vestibular nuclear area, cerebellar ventral vermis and floccular lobe), cardiorespiratory control (medulla and pons), and vision (dorsal occipital cortex, superior colliculi and lateral geniculate body). Conversely, blood flow to regions related to hearing (cochlear nuclei, inferior colliculi and temporal cortex) and smell (olfactory bulbs and rhinencephalon) were unaltered by exercise and associated with increases in vascular resistance. 5. The data indicate that blood flow increases as a function of exercise intensity to several areas of the brain associated with integrating sensory input and motor output (anterior and dorsal cerebellar vermis) and the maintenance of equilibrium (vestibular nuclei). Additionally, there was an intensity-dependent decrease of vascular resistance in the dorsal cerebellar vermis.

  17. Regionally distinct responses of microglia and glial progenitor cells to whole brain irradiation in adult and aging rats.

    Science.gov (United States)

    Hua, Kun; Schindler, Matthew K; McQuail, Joseph A; Forbes, M Elizabeth; Riddle, David R

    2012-01-01

    Radiation therapy has proven efficacy for treating brain tumors and metastases. Higher doses and larger treatment fields increase the probability of eliminating neoplasms and preventing reoccurrence, but dose and field are limited by damage to normal tissues. Normal tissue injury is greatest during development and in populations of proliferating cells but also occurs in adults and older individuals and in non-proliferative cell populations. To better understand radiation-induced normal tissue injury and how it may be affected by aging, we exposed young adult, middle-aged, and old rats to 10 Gy of whole brain irradiation and assessed in gray- and white matter the responses of microglia, the primary cellular mediators of radiation-induced neuroinflammation, and oligodendrocyte precursor cells, the largest population of proliferating cells in the adult brain. We found that aging and/or irradiation caused only a few microglia to transition to the classically "activated" phenotype, e.g., enlarged cell body, few processes, and markers of phagocytosis, that is seen following more damaging neural insults. Microglial changes in response to aging and irradiation were relatively modest and three markers of reactivity - morphology, proliferation, and expression of the lysosomal marker CD68- were regulated largely independently within individual cells. Proliferation of oligodendrocyte precursors did not appear to be altered during normal aging but increased following irradiation. The impacts of irradiation and aging on both microglia and oligodendrocyte precursors were heterogeneous between white- and gray matter and among regions of gray matter, indicating that there are regional regulators of the neural response to brain irradiation. By several measures, the CA3 region of the hippocampus appeared to be differentially sensitive to effects of aging and irradiation. The changes assessed here likely contribute to injury following inflammatory challenges like brain irradiation and

  18. Regionally distinct responses of microglia and glial progenitor cells to whole brain irradiation in adult and aging rats.

    Directory of Open Access Journals (Sweden)

    Kun Hua

    Full Text Available Radiation therapy has proven efficacy for treating brain tumors and metastases. Higher doses and larger treatment fields increase the probability of eliminating neoplasms and preventing reoccurrence, but dose and field are limited by damage to normal tissues. Normal tissue injury is greatest during development and in populations of proliferating cells but also occurs in adults and older individuals and in non-proliferative cell populations. To better understand radiation-induced normal tissue injury and how it may be affected by aging, we exposed young adult, middle-aged, and old rats to 10 Gy of whole brain irradiation and assessed in gray- and white matter the responses of microglia, the primary cellular mediators of radiation-induced neuroinflammation, and oligodendrocyte precursor cells, the largest population of proliferating cells in the adult brain. We found that aging and/or irradiation caused only a few microglia to transition to the classically "activated" phenotype, e.g., enlarged cell body, few processes, and markers of phagocytosis, that is seen following more damaging neural insults. Microglial changes in response to aging and irradiation were relatively modest and three markers of reactivity - morphology, proliferation, and expression of the lysosomal marker CD68- were regulated largely independently within individual cells. Proliferation of oligodendrocyte precursors did not appear to be altered during normal aging but increased following irradiation. The impacts of irradiation and aging on both microglia and oligodendrocyte precursors were heterogeneous between white- and gray matter and among regions of gray matter, indicating that there are regional regulators of the neural response to brain irradiation. By several measures, the CA3 region of the hippocampus appeared to be differentially sensitive to effects of aging and irradiation. The changes assessed here likely contribute to injury following inflammatory challenges like

  19. Brain Death,Concept and Criteria

    Institute of Scientific and Technical Information of China (English)

    2009-01-01

    The concept of brain death originated in France. In 1959, the French scholars P. Mollaret and M. Goulon proposed the concept of "coma de- passe" or "brain death" for the first time and reported 23 cases with such symptoms. The first guidelines (the Harvard criteria) for diagnosing brain death was established in 1968, defining brain death

  20. Brain region-specific perfluoroalkylated sulfonate (PFSA) and carboxylic acid (PFCA) accumulation and neurochemical biomarker responses in east Greenland polar bears (Ursus maritimus)

    DEFF Research Database (Denmark)

    Pedersen, Kathrine Eggers; Basu, Niladri; Letcher, Robert J.

    2015-01-01

    to bioaccumulate in lipid rich tissues of the brain among other tissues such as liver, and can reach high concentrations in top predators including the polar bear. PFCA and PFSA bioaccummulation in the brain has the potential to pose neurotoxic effects and therefore we conducted a study to investigate...... if variations in neurochemical transmitter systems i.e. the cholinergic, glutaminergic, dopaminergic and GABAergic, could be related to brain-specific bioaccumulation of PFASs in East Greenland polar bears. Nine brain regions from nine polar bears were analyzed for enzyme activity (monoamine oxidase (MAO...... regions, whereas GS activity was positively correlated with PFASs primarily in occipital lobe. Results from the present study support the hypothesis that PFAS concentrations in polar bears from East Greenland have exceeded the threshold limits for neurochemical alterations. It is not known whether...

  1. Automatic Semantic Segmentation of Brain Gliomas from MRI Images Using a Deep Cascaded Neural Network.

    Science.gov (United States)

    Cui, Shaoguo; Mao, Lei; Jiang, Jingfeng; Liu, Chang; Xiong, Shuyu

    2018-01-01

    Brain tumors can appear anywhere in the brain and have vastly different sizes and morphology. Additionally, these tumors are often diffused and poorly contrasted. Consequently, the segmentation of brain tumor and intratumor subregions using magnetic resonance imaging (MRI) data with minimal human interventions remains a challenging task. In this paper, we present a novel fully automatic segmentation method from MRI data containing in vivo brain gliomas. This approach can not only localize the entire tumor region but can also accurately segment the intratumor structure. The proposed work was based on a cascaded deep learning convolutional neural network consisting of two subnetworks: (1) a tumor localization network (TLN) and (2) an intratumor classification network (ITCN). The TLN, a fully convolutional network (FCN) in conjunction with the transfer learning technology, was used to first process MRI data. The goal of the first subnetwork was to define the tumor region from an MRI slice. Then, the ITCN was used to label the defined tumor region into multiple subregions. Particularly, ITCN exploited a convolutional neural network (CNN) with deeper architecture and smaller kernel. The proposed approach was validated on multimodal brain tumor segmentation (BRATS 2015) datasets, which contain 220 high-grade glioma (HGG) and 54 low-grade glioma (LGG) cases. Dice similarity coefficient (DSC), positive predictive value (PPV), and sensitivity were used as evaluation metrics. Our experimental results indicated that our method could obtain the promising segmentation results and had a faster segmentation speed. More specifically, the proposed method obtained comparable and overall better DSC values (0.89, 0.77, and 0.80) on the combined (HGG + LGG) testing set, as compared to other methods reported in the literature. Additionally, the proposed approach was able to complete a segmentation task at a rate of 1.54 seconds per slice.

  2. Deep brain stimulation for Parkinson's disease: defining the optimal location within the subthalamic nucleus.

    Science.gov (United States)

    Bot, Maarten; Schuurman, P Richard; Odekerken, Vincent J J; Verhagen, Rens; Contarino, Fiorella Maria; De Bie, Rob M A; van den Munckhof, Pepijn

    2018-05-01

    Individual motor improvement after deep brain stimulation (DBS) of the subthalamic nucleus (STN) for Parkinson's disease (PD) varies considerably. Stereotactic targeting of the dorsolateral sensorimotor part of the STN is considered paramount for maximising effectiveness, but studies employing the midcommissural point (MCP) as anatomical reference failed to show correlation between DBS location and motor improvement. The medial border of the STN as reference may provide better insight in the relationship between DBS location and clinical outcome. Motor improvement after 12 months of 65 STN DBS electrodes was categorised into non-responding, responding and optimally responding body-sides. Stereotactic coordinates of optimal electrode contacts relative to both medial STN border and MCP served to define theoretic DBS 'hotspots'. Using the medial STN border as reference, significant negative correlation (Pearson's correlation -0.52, P<0.01) was found between the Euclidean distance from the centre of stimulation to this DBS hotspot and motor improvement. This hotspot was located at 2.8 mm lateral, 1.7 mm anterior and 2.5 mm superior relative to the medial STN border. Using MCP as reference, no correlation was found. The medial STN border proved superior compared with MCP as anatomical reference for correlation of DBS location and motor improvement, and enabled defining an optimal DBS location within the nucleus. We therefore propose the medial STN border as a better individual reference point than the currently used MCP on preoperative stereotactic imaging, in order to obtain optimal and thus less variable motor improvement for individual patients with PD following STN DBS. © Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2018. All rights reserved. No commercial use is permitted unless otherwise expressly granted.

  3. Frequency-dependent brain regional homogeneity alterations in patients with mild cognitive impairment during working memory state relative to resting state

    Directory of Open Access Journals (Sweden)

    Pengyun eWang

    2016-03-01

    Full Text Available Several studies have reported working memory deficits in patients with mild cognitive impairment (MCI. However, previous studies investigating the neural mechanisms of MCI have primarily focused on brain activity alterations during working memory tasks. No study to date has compared brain network alterations in the working memory state between MCI patients and normal control subjects. Therefore, using the index of regional homogeneity (ReHo, we explored brain network impairments in MCI patients during a working memory task relative to the resting state, and identified frequency-dependent effects in separate frequency bands.Our results indicate that, in MCI patients, ReHo is altered in the posterior cingulate cortex in the slow-3 band (0.073–0.198 Hz, and in the bottom of the right occipital lobe and part of the right cerebellum, the right thalamus, a diffusing region in the bilateral prefrontal cortex, the left and right parietal-occipital regions, and the right angular gyrus in the slow-5 band (0.01–0.027 Hz. Furthermore, in normal controls, the value of ReHo in clusters belonging to the default mode network decreased, while the value of ReHo in clusters belonging to the attentional network increased during the task state. However, this pattern was reversed in MCI patients, and was associated with decreased working memory performance. In addition, we identified altered functional connectivity of the abovementioned regions with other parts of the brain in MCI patients.This is the first study to compare frequency-dependent alterations of ReHo in MCI patients between resting and working memory states. The results provide a new perspective regarding the neural mechanisms of working memory deficits in MCI patients, and extend our knowledge of altered brain patterns in resting and task-evoked states.

  4. Validating computationally predicted TMS stimulation areas using direct electrical stimulation in patients with brain tumors near precentral regions.

    Science.gov (United States)

    Opitz, Alexander; Zafar, Noman; Bockermann, Volker; Rohde, Veit; Paulus, Walter

    2014-01-01

    The spatial extent of transcranial magnetic stimulation (TMS) is of paramount interest for all studies employing this method. It is generally assumed that the induced electric field is the crucial parameter to determine which cortical regions are excited. While it is difficult to directly measure the electric field, one usually relies on computational models to estimate the electric field distribution. Direct electrical stimulation (DES) is a local brain stimulation method generally considered the gold standard to map structure-function relationships in the brain. Its application is typically limited to patients undergoing brain surgery. In this study we compare the computationally predicted stimulation area in TMS with the DES area in six patients with tumors near precentral regions. We combine a motor evoked potential (MEP) mapping experiment for both TMS and DES with realistic individual finite element method (FEM) simulations of the electric field distribution during TMS and DES. On average, stimulation areas in TMS and DES show an overlap of up to 80%, thus validating our computational physiology approach to estimate TMS excitation volumes. Our results can help in understanding the spatial spread of TMS effects and in optimizing stimulation protocols to more specifically target certain cortical regions based on computational modeling.

  5. Dose-response assessment of tariquidar and elacridar and regional quantification of P-glycoprotein inhibition at the rat blood-brain barrier using (R)-[11C]verapamil PET

    International Nuclear Information System (INIS)

    Kuntner, Claudia; Wanek, Thomas; Stundner, Gloria; Bankstahl, Jens P.; Bankstahl, Marion; Loescher, Wolfgang; Stanek, Johann; Mueller, Markus; Karch, Rudolf; Brauner, Rebecca; Meier, Martin; Ding, Xiaoqi; Langer, Oliver

    2010-01-01

    Overactivity of the multidrug efflux transporter P-glycoprotein (P-gp) at the blood-brain barrier (BBB) is believed to play an important role in resistance to central nervous system drug treatment. (R)-[ 11 C]verapamil (VPM) PET can be used to measure the function of P-gp at the BBB, but low brain uptake of VPM hampers the mapping of regional differences in cerebral P-gp function and expression. The aim of this study was to evaluate the dose-response relationship of two potent P-gp inhibitors and to investigate if increased brain uptake of VPM mediated by P-gp inhibition can be used to assess regional differences in P-gp activity. Two groups of Sprague-Dawley rats (n = 12) underwent single VPM PET scans at 120 min after administration of different doses of the P-gp inhibitors tariquidar and elacridar. In an additional six rats, paired VPM PET scans were performed before and after administration of 3 mg/kg tariquidar. Inhibitor administration resulted in an up to 11-fold increase in VPM brain distribution volumes (DV) with half-maximum effective dose (ED 50 ) values of 3.0 ± 0.2 and 1.2 ± 0.1 mg/kg for tariquidar and elacridar, respectively. In paired PET scans, 3 mg/kg tariquidar resulted in regionally different enhancement of brain activity distribution, with lowest DV in cerebellum and highest DV in thalamus. Our data show that tariquidar and elacridar are able to increase VPM brain distribution in rat brain up to 11-fold over baseline at maximum effective doses, with elacridar being about three times more potent than tariquidar. Regional differences in tariquidar-induced modulation of VPM brain uptake point to regional differences in cerebral P-gp function and expression in rat brain. (orig.)

  6. Radiopharmaceuticals for brain - SPECT

    International Nuclear Information System (INIS)

    Moretti, J.L.

    1992-01-01

    Perfusion tracers for brain SPECT imaging suitable for regional cerebral blood flow measurement and regional cerebral blood volume determination, with respect to their ability to pass the blood-brain-barrier, are described. Problems related t the use of specific radiotracers to map receptors distribution in the brain are also discussed in this lecture. 9 figs, 6 tabs

  7. Total and regional brain volumes in a population-based normative sample from 4 to 18 years: the NIH MRI Study of Normal Brain Development.

    Science.gov (United States)

    2012-01-01

    Using a population-based sampling strategy, the National Institutes of Health (NIH) Magnetic Resonance Imaging Study of Normal Brain Development compiled a longitudinal normative reference database of neuroimaging and correlated clinical/behavioral data from a demographically representative sample of healthy children and adolescents aged newborn through early adulthood. The present paper reports brain volume data for 325 children, ages 4.5-18 years, from the first cross-sectional time point. Measures included volumes of whole-brain gray matter (GM) and white matter (WM), left and right lateral ventricles, frontal, temporal, parietal and occipital lobe GM and WM, subcortical GM (thalamus, caudate, putamen, and globus pallidus), cerebellum, and brainstem. Associations with cross-sectional age, sex, family income, parental education, and body mass index (BMI) were evaluated. Key observations are: 1) age-related decreases in lobar GM most prominent in parietal and occipital cortex; 2) age-related increases in lobar WM, greatest in occipital, followed by the temporal lobe; 3) age-related trajectories predominantly curvilinear in females, but linear in males; and 4) small systematic associations of brain tissue volumes with BMI but not with IQ, family income, or parental education. These findings constitute a normative reference on regional brain volumes in children and adolescents.

  8. Acute and chronic glucocorticoid treatments regulate astrocyte-enriched mRNAs in multiple brain regions in vivo

    Directory of Open Access Journals (Sweden)

    Bradley S. Carter

    2013-08-01

    Full Text Available Previous studies have primarily interpreted gene expression regulation by glucocorticoids in the brain in terms of impact on neurons; however, less is known about the corresponding impact of glucocorticoids on glia and specifically astrocytes in vivo. Recent microarray experiments have identified glucocorticoid-sensitive mRNAs in primary astrocyte cell culture, including a number of mRNAs that have reported astrocyte-enriched expression patterns relative to other brain cell types. Here, we have tested whether elevations of glucocorticoids regulate a subset of these mRNAs in vivo following acute and chronic corticosterone exposure in adult mice. Acute corticosterone exposure was achieved by a single injection of 10 mg/kg corticosterone, and tissue samples were harvested two hours post-injection. Chronic corticosterone exposure was achieved by administering 10 mg/mL corticosterone via drinking water for two weeks. Gene expression was then assessed in two brain regions associated with glucocorticoid action (prefrontal cortex and hippocampus by qPCR and by in situ hybridization. The majority of measured mRNAs regulated by glucocorticoids in astrocytes in vitro were similarly regulated by acute and/or chronic glucocorticoid exposure in vivo. In addition, the expression levels for mRNAs regulated in at least one corticosterone exposure condition (acute/chronic demonstrated moderate positive correlation between the two conditions by brain region. In situ hybridization analyses suggest that select mRNAs are regulated by chronic corticosterone exposure specifically in astroctyes based on (1 similar general expression patterns between corticosterone-treated and vehicle-treated animals and (2 similar expression patterns to the pan-astrocyte marker Aldh1l1. Our findings demonstrate that glucocorticoids regulate astrocyte-enriched mRNAs in vivo and suggest that glucocorticoids regulate gene expression in the brain in a cell type-dependent fashion.

  9. Assessing denoising strategies to increase signal to noise ratio in spinal cord and in brain cortical and subcortical regions

    Science.gov (United States)

    Maugeri, L.; Moraschi, M.; Summers, P.; Favilla, S.; Mascali, D.; Cedola, A.; Porro, C. A.; Giove, F.; Fratini, M.

    2018-02-01

    Functional Magnetic Resonance Imaging (fMRI) based on Blood Oxygenation Level Dependent (BOLD) contrast has become one of the most powerful tools in neuroscience research. On the other hand, fMRI approaches have seen limited use in the study of spinal cord and subcortical brain regions (such as the brainstem and portions of the diencephalon). Indeed obtaining good BOLD signal in these areas still represents a technical and scientific challenge, due to poor control of physiological noise and to a limited overall quality of the functional series. A solution can be found in the combination of optimized experimental procedures at acquisition stage, and well-adapted artifact mitigation procedures in the data processing. In this framework, we studied two different data processing strategies to reduce physiological noise in cortical and subcortical brain regions and in the spinal cord, based on the aCompCor and RETROICOR denoising tools respectively. The study, performed in healthy subjects, was carried out using an ad hoc isometric motor task. We observed an increased signal to noise ratio in the denoised functional time series in the spinal cord and in the subcortical brain region.

  10. Simplified methods for in vivo measurement of acetylcholinesterase activity in rodent brain

    Energy Technology Data Exchange (ETDEWEB)

    Kilbourn, Michael R. E-mail: mkilbour@umich.edu; Sherman, Phillip S.; Snyder, Scott E

    1999-07-01

    Simplified methods for in vivo studies of acetylcholinesterase (AChE) activity in rodent brain were evaluated using N-[{sup 11}C]methylpiperidinyl propionate ([{sup 11}C]PMP) as an enzyme substrate. Regional mouse brain distributions were determined at 1 min (representing initial brain uptake) and 30 min (representing trapped product) after intravenous [{sup 11}C]PMP administration. Single time point tissue concentrations (percent injected dose/gram at 30 min), tissue concentration ratios (striatum/cerebellum and striatum/cortex ratios at 30 min), and regional tissue retention fractions (defined as percent injected dose 30 min/percent injected dose 1 min) were evaluated as measures of AChE enzymatic activity in mouse brain. Studies were carried out in control animals and after dosing with phenserine, a selective centrally active AChE inhibitor; neostigmine, a peripheral cholinesterase inhibitor; and a combination of the two drugs. In control and phenserine-treated animals, absolute tissue concentrations and regional retention fractions provide good measures of dose-dependent inhibition of brain AChE; tissue concentration ratios, however, provide erroneous conclusions. Peripheral inhibition of cholinesterases, which changes the blood pharmacokinetics of the radiotracer, diminishes the sensitivity of all measures to detect changes in central inhibition of the enzyme. We conclude that certain simple measures of AChE hydrolysis rates for [{sup 11}C]PMP are suitable for studies where alterations of the peripheral blood metabolism of the tracer are kept to a minimum.

  11. Regional brain response to visual food cues is a marker of satiety that predicts food choice1234

    Science.gov (United States)

    Mehta, Sonya; Melhorn, Susan J; Smeraglio, Anne; Tyagi, Vidhi; Grabowski, Thomas; Schwartz, Michael W

    2012-01-01

    Background: Neuronal processes that underlie the subjective experience of satiety after a meal are not well defined. Objective: We investigated how satiety alters the perception of and neural response to visual food cues. Design: Normal-weight participants (10 men, 13 women) underwent 2 fMRI scans while viewing images of high-calorie food that was previously rated as incompatible with weight loss and “fattening” and low-calorie, “nonfattening” food. After a fasting fMRI scan, participants ate a standardized breakfast and underwent reimaging at a randomly assigned time 15–300 min after breakfast to vary the degree of satiety. Measures of subjective appetite, food appeal, and ad libitum food intake (measured after the second fMRI scan) were correlated with activation by “fattening” (compared with “nonfattening”) food cues in a priori regions of interest. Results: Greater hunger correlated with higher appeal ratings of “fattening” (r = 0.46, P = 0.03) but not “nonfattening” (r = −0.20, P = 0.37) foods. Fasting amygdalar activation was negatively associated with fullness (left: r = −0.52; right: r = −0.58; both P ≤ 0.01), whereas postbreakfast fullness was positively correlated with activation in the dorsal striatum (right: r = 0.44; left: r = 0.45; both P foods with higher fat content. Conclusions: Postmeal satiety is shown in regional brain activation by images of high-calorie foods. Regions including the amygdala, nucleus accumbens, and dorsal striatum may alter perception of, and reduce motivation to consume, energy-rich foods, ultimately driving food choice. This trial was registered at clinicaltrials.gov as NCT01631045. PMID:22990034

  12. Revealing the cerebral regions and networks mediating vulnerability to depression: oxidative metabolism mapping of rat brain.

    Science.gov (United States)

    Harro, Jaanus; Kanarik, Margus; Kaart, Tanel; Matrov, Denis; Kõiv, Kadri; Mällo, Tanel; Del Río, Joaquin; Tordera, Rosa M; Ramirez, Maria J

    2014-07-01

    The large variety of available animal models has revealed much on the neurobiology of depression, but each model appears as specific to a significant extent, and distinction between stress response, pathogenesis of depression and underlying vulnerability is difficult to make. Evidence from epidemiological studies suggests that depression occurs in biologically predisposed subjects under impact of adverse life events. We applied the diathesis-stress concept to reveal brain regions and functional networks that mediate vulnerability to depression and response to chronic stress by collapsing data on cerebral long term neuronal activity as measured by cytochrome c oxidase histochemistry in distinct animal models. Rats were rendered vulnerable to depression either by partial serotonergic lesion or by maternal deprivation, or selected for a vulnerable phenotype (low positive affect, low novelty-related activity or high hedonic response). Environmental adversity was brought about by applying chronic variable stress or chronic social defeat. Several brain regions, most significantly median raphe, habenula, retrosplenial cortex and reticular thalamus, were universally implicated in long-term metabolic stress response, vulnerability to depression, or both. Vulnerability was associated with higher oxidative metabolism levels as compared to resilience to chronic stress. Chronic stress, in contrast, had three distinct patterns of effect on oxidative metabolism in vulnerable vs. resilient animals. In general, associations between regional activities in several brain circuits were strongest in vulnerable animals, and chronic stress disrupted this interrelatedness. These findings highlight networks that underlie resilience to stress, and the distinct response to stress that occurs in vulnerable subjects. Copyright © 2014 Elsevier B.V. All rights reserved.

  13. Synapsin I (Protein I) in different brain regions in senile dementia of Alzheimer type and in multiinfarct dementia. [Radioimmunoassay

    Energy Technology Data Exchange (ETDEWEB)

    Adolfsson, R; Alafuzoff, I; Winblad, B [Umeaa Univ. (Sweden); Perdahl, E; Albert, K A; Nestler, E J; Greengard, P [Rockefeller Univ., New York (USA)

    1984-01-01

    Synapsin I (Protein I), a neuron-specfic phosphoprotein enriched in presynaptic nerve terminals, has been used as a quantitative marker for the density of nerve terminals in five brain regions (caudate nucleus, cingulate gyrus, hippocampus, mesencephalon and putamen) from patients who had suffered from Alzheimer disease/senile dementia of Alzheimer type (AD/SDAT), from patients with multi-infarct dementia (MID), and from agematched controls. Samples were obtained at autopsy. Lower levels of Synapsin I were observed in the hippocampus of patients with AD/SDAT but not with MID. There were no significant differences in Synapsin I levels between patients and controls in any of the other four brain regions examined.

  14. Analysis of Regional Cerebral Blood Flow Using 99mTc-HMPAO Brain SPECT in Senile Dementia of Alzheimer Type

    International Nuclear Information System (INIS)

    Lee, Myung Hae; Lee, Myung Chul; Koh, Chang Soon; Roh, Jae Kyu; Woo, Chong In

    1988-01-01

    99m Tc-HMPAO brain SPECT studies were performed in 11 patients with Alzheimer's disease, 7 patients with psychological depression and 12 normal controls. Changes of regional cerebral blood flow was semiquantitatively analyzed and the results were as follows. 1) In 11 patients with Alzheimer's disease, significant reduction of regional cerebral blood flow was found In both temporoparietal areas. 2) Relative perfusion between cerebral hemispheres was rather symmetrical in patient with Alzheimer's disease. 3) All patients with depression showed normal SPECT findings. As for conclusion, 99m Tc-HMPAO brain SPECT seemed to be a valuable method for clinical assessment and management of patients with Alzheimer's disease.

  15. [The process of defining the competence profile of the healthcare professions manager in the Veneto Region].

    Science.gov (United States)

    Costa, Claudio; Roncoroni, Elisabetta; Saiani, Luisa; Stevanin, Simone; Fanton, Elena; Mantoan, Domenico

    2018-01-01

    Presented here is the approach used by a multidisciplinary working group fo the drafting of the "core" competence profile of the healthcare professions manager in the Veneto Region. Defining a competence profile allows for specifying a standard for measuring the skills acquired by a professional and the gap level from what is expected by the organization, as well as orienting the preparatory education to carry out the related role.

  16. Brain parenchymal damage in neuromyelitis optica spectrum disorder - A multimodal MRI study

    Energy Technology Data Exchange (ETDEWEB)

    Pache, F.; Paul, F. [Max Delbrueck Center for Molecular Medicine and Charite Universitaetsmedizin Berlin, NeuroCure Clinical Research Center and Experimental and Clinical Research Center, Berlin (Germany); Charite Universitaetsmedizin Berlin, Department of Neurology, Berlin (Germany); Zimmermann, H.; Lacheta, A.; Papazoglou, S.; Kuchling, J.; Wuerfel, J.; Brandt, A.U. [Max Delbrueck Center for Molecular Medicine and Charite Universitaetsmedizin Berlin, NeuroCure Clinical Research Center and Experimental and Clinical Research Center, Berlin (Germany); Finke, C. [Charite Universitaetsmedizin Berlin, Department of Neurology, Berlin (Germany); Humboldt-Universitaet zu Berlin, Berlin School of Mind and Brain, Berlin (Germany); Hamm, B. [Charite Universitaetsmedizin Berlin, Department of Radiology, Berlin (Germany); Ruprecht, K. [Charite Universitaetsmedizin Berlin, Department of Neurology, Berlin (Germany); Scheel, M. [Max Delbrueck Center for Molecular Medicine and Charite Universitaetsmedizin Berlin, NeuroCure Clinical Research Center and Experimental and Clinical Research Center, Berlin (Germany); Charite Universitaetsmedizin Berlin, Department of Radiology, Berlin (Germany)

    2016-12-15

    To investigate different brain regions for grey (GM) and white matter (WM) damage in a well-defined cohort of neuromyelitis optica spectrum disorder (NMOSD) patients and compare advanced MRI techniques (VBM, Subcortical and cortical analyses (Freesurfer), and DTI) for their ability to detect damage in NMOSD. We analyzed 21 NMOSD patients and 21 age and gender matched control subjects. VBM (GW/WM) and DTI whole brain (TBSS) analyses were performed at different statistical thresholds to reflect different statistical approaches in previous studies. In an automated atlas-based approach, Freesurfer and DTI results were compared between NMOSD and controls. DTI TBSS and DTI atlas based analysis demonstrated microstructural impairment only within the optic radiation or in regions associated with the optic radiation (posterior thalamic radiation p < 0.001, 6.9 % reduction of fractional anisotropy). VBM demonstrated widespread brain GM and WM reduction, but only at exploratory statistical thresholds, with no differences remaining after correction for multiple comparisons. Freesurfer analysis demonstrated no group differences. NMOSD specific parenchymal brain damage is predominantly located in the optic radiation, likely due to a secondary degeneration caused by ON. In comparison, DTI appears to be the most reliable and sensitive technique for brain damage detection in NMOSD. (orig.)

  17. Brain parenchymal damage in neuromyelitis optica spectrum disorder - A multimodal MRI study

    International Nuclear Information System (INIS)

    Pache, F.; Paul, F.; Zimmermann, H.; Lacheta, A.; Papazoglou, S.; Kuchling, J.; Wuerfel, J.; Brandt, A.U.; Finke, C.; Hamm, B.; Ruprecht, K.; Scheel, M.

    2016-01-01

    To investigate different brain regions for grey (GM) and white matter (WM) damage in a well-defined cohort of neuromyelitis optica spectrum disorder (NMOSD) patients and compare advanced MRI techniques (VBM, Subcortical and cortical analyses (Freesurfer), and DTI) for their ability to detect damage in NMOSD. We analyzed 21 NMOSD patients and 21 age and gender matched control subjects. VBM (GW/WM) and DTI whole brain (TBSS) analyses were performed at different statistical thresholds to reflect different statistical approaches in previous studies. In an automated atlas-based approach, Freesurfer and DTI results were compared between NMOSD and controls. DTI TBSS and DTI atlas based analysis demonstrated microstructural impairment only within the optic radiation or in regions associated with the optic radiation (posterior thalamic radiation p < 0.001, 6.9 % reduction of fractional anisotropy). VBM demonstrated widespread brain GM and WM reduction, but only at exploratory statistical thresholds, with no differences remaining after correction for multiple comparisons. Freesurfer analysis demonstrated no group differences. NMOSD specific parenchymal brain damage is predominantly located in the optic radiation, likely due to a secondary degeneration caused by ON. In comparison, DTI appears to be the most reliable and sensitive technique for brain damage detection in NMOSD. (orig.)

  18. Toluene effects on oxidative stress in brain regions of young-adult, middle-age, and senescent Brown Norway rats

    International Nuclear Information System (INIS)

    Kodavanti, Prasada Rao S.; Royland, Joyce E.; Richards, Judy E.; Besas, Jonathan; MacPhail, Robert C.

    2011-01-01

    The influence of aging on susceptibility to environmental contaminants is not well understood. To extend knowledge in this area, we examined effects in rat brain of the volatile organic compound, toluene. The objective was to test whether oxidative stress (OS) plays a role in the adverse effects caused by toluene exposure, and if so, if effects are age-dependent. OS parameters were selected to measure the production of reactive oxygen species (NADPH Quinone oxidoreductase 1 (NQO1), NADH Ubiquinone reductase (UBIQ-RD)), antioxidant homeostasis (total antioxidant substances (TAS), superoxide dismutase (SOD), γ-glutamylcysteine synthetase (γ-GCS), glutathione transferase (GST), glutathione peroxidase (GPX), glutathione reductase (GRD)), and oxidative damage (total aconitase and protein carbonyls). In this study, Brown Norway rats (4, 12, and 24 months) were dosed orally with toluene (0, 0.65 or 1 g/kg) in corn oil. Four hours later, frontal cortex, cerebellum, striatum, and hippocampus were dissected, quick frozen on dry ice, and stored at − 80 °C until analysis. Some parameters of OS were found to increase with age in select brain regions. Toluene exposure also resulted in increased OS in select brain regions. For example, an increase in NQO1 activity was seen in frontal cortex and cerebellum of 4 and 12 month old rats following toluene exposure, but only in the hippocampus of 24 month old rats. Similarly, age and toluene effects on glutathione enzymes were varied and brain-region specific. Markers of oxidative damage reflected changes in oxidative stress. Total aconitase activity was increased by toluene in frontal cortex and cerebellum at 12 and 24 months, respectively. Protein carbonyls in both brain regions and in all age groups were increased by toluene, but step-down analyses indicated toluene effects were statistically significant only in 12 month old rats. These results indicate changes in OS parameters with age and toluene exposure resulted in oxidative

  19. Use of Multichannel Near Infrared Spectroscopy to Study Relationships Between Brain Regions and Neurocognitive Tasks of Selective/Divided Attention and 2-Back Working Memory.

    Science.gov (United States)

    Tomita, Nozomi; Imai, Shoji; Kanayama, Yusuke; Kawashima, Issaku; Kumano, Hiroaki

    2017-06-01

    While dichotic listening (DL) was originally intended to measure bottom-up selective attention, it has also become a tool for measuring top-down selective attention. This study investigated the brain regions related to top-down selective and divided attention DL tasks and a 2-back task using alphanumeric and Japanese numeric sounds. Thirty-six healthy participants underwent near-infrared spectroscopy scanning while performing a top-down selective attentional DL task, a top-down divided attentional DL task, and a 2-back task. Pearson's correlations were calculated to show relationships between oxy-Hb concentration in each brain region and the score of each cognitive task. Different brain regions were activated during the DL and 2-back tasks. Brain regions activated in the top-down selective attention DL task were the left inferior prefrontal gyrus and left pars opercularis. The left temporopolar area was activated in the top-down divided attention DL task, and the left frontopolar area and left dorsolateral prefrontal cortex were activated in the 2-back task. As further evidence for the finding that each task measured different cognitive and brain area functions, neither the percentages of correct answers for the three tasks nor the response times for the selective attentional task and the divided attentional task were correlated to one another. Thus, the DL and 2-back tasks used in this study can assess multiple areas of cognitive, brain-related dysfunction to explore their relationship to different psychiatric and neurodevelopmental disorders.

  20. Changes of brain metabolite concentrations during maturation in different brain regions measured by chemical shift imaging

    International Nuclear Information System (INIS)

    Bueltmann, Eva; Lanfermann, Heinrich; Naegele, Thomas; Klose, Uwe

    2017-01-01

    We examined the effect of maturation on the regional distribution of brain metabolite concentrations using multivoxel chemical shift imaging. From our pool of pediatric MRI examinations, we retrospectively selected patients showing a normal cerebral MRI scan or no pathologic signal abnormalities at the level of the two-dimensional 1H MRS-CSI sequence and an age-appropriate global neurological development, except for focal neurological deficits. Seventy-one patients (4.5 months-20 years) were identified. Using LC Model, spectra were evaluated from voxels in the white matter, caudate head, and corpus callosum. The concentration of total N-acetylaspartate increased in all regions during infancy and childhood except in the right caudate head where it remained constant. The concentration of total creatine decreased in the caudate nucleus and splenium and minimally in the frontal white matter and genu. It remained largely constant in the parietal white matter. The concentration of choline-containing compounds had the tendency to decrease in all regions except in the parietal white matter where it remained constant. The concentration of myoinositol decreased slightly in the splenium and right frontal white matter, remained constant on the left side and in the caudate nucleus, and rose slightly in the parietal white matter and genu. CSI determined metabolite concentrations in multiple cerebral regions during routine MRI. The obtained data will be helpful in future pediatric CSI measurements deciding whether the ratios of the main metabolites are within the range of normal values or have to be considered as probably pathologic. (orig.)

  1. Changes of brain metabolite concentrations during maturation in different brain regions measured by chemical shift imaging.

    Science.gov (United States)

    Bültmann, Eva; Nägele, Thomas; Lanfermann, Heinrich; Klose, Uwe

    2017-01-01

    We examined the effect of maturation on the regional distribution of brain metabolite concentrations using multivoxel chemical shift imaging. From our pool of pediatric MRI examinations, we retrospectively selected patients showing a normal cerebral MRI scan or no pathologic signal abnormalities at the level of the two-dimensional 1H MRS-CSI sequence and an age-appropriate global neurological development, except for focal neurological deficits. Seventy-one patients (4.5 months-20 years) were identified. Using LC Model, spectra were evaluated from voxels in the white matter, caudate head, and corpus callosum. The concentration of total N-acetylaspartate increased in all regions during infancy and childhood except in the right caudate head where it remained constant. The concentration of total creatine decreased in the caudate nucleus and splenium and minimally in the frontal white matter and genu. It remained largely constant in the parietal white matter. The concentration of choline-containing compounds had the tendency to decrease in all regions except in the parietal white matter where it remained constant. The concentration of myoinositol decreased slightly in the splenium and right frontal white matter, remained constant on the left side and in the caudate nucleus, and rose slightly in the parietal white matter and genu. CSI determined metabolite concentrations in multiple cerebral regions during routine MRI. The obtained data will be helpful in future pediatric CSI measurements deciding whether the ratios of the main metabolites are within the range of normal values or have to be considered as probably pathologic.

  2. Changes of brain metabolite concentrations during maturation in different brain regions measured by chemical shift imaging

    Energy Technology Data Exchange (ETDEWEB)

    Bueltmann, Eva; Lanfermann, Heinrich [Hannover Medical School, Institute of Diagnostic and Interventional Neuroradiology, Hannover (Germany); Naegele, Thomas [University of Tuebingen, Department of Diagnostic and Interventional Neuroradiology, Radiological University Hospital, Tuebingen (Germany); Klose, Uwe [University of Tuebingen, Section of Experimental MR of the CNS, Department of Neuroradiology, Radiological University Hospital, Tuebingen (Germany)

    2017-01-15

    We examined the effect of maturation on the regional distribution of brain metabolite concentrations using multivoxel chemical shift imaging. From our pool of pediatric MRI examinations, we retrospectively selected patients showing a normal cerebral MRI scan or no pathologic signal abnormalities at the level of the two-dimensional 1H MRS-CSI sequence and an age-appropriate global neurological development, except for focal neurological deficits. Seventy-one patients (4.5 months-20 years) were identified. Using LC Model, spectra were evaluated from voxels in the white matter, caudate head, and corpus callosum. The concentration of total N-acetylaspartate increased in all regions during infancy and childhood except in the right caudate head where it remained constant. The concentration of total creatine decreased in the caudate nucleus and splenium and minimally in the frontal white matter and genu. It remained largely constant in the parietal white matter. The concentration of choline-containing compounds had the tendency to decrease in all regions except in the parietal white matter where it remained constant. The concentration of myoinositol decreased slightly in the splenium and right frontal white matter, remained constant on the left side and in the caudate nucleus, and rose slightly in the parietal white matter and genu. CSI determined metabolite concentrations in multiple cerebral regions during routine MRI. The obtained data will be helpful in future pediatric CSI measurements deciding whether the ratios of the main metabolites are within the range of normal values or have to be considered as probably pathologic. (orig.)

  3. Uniform distributions of glucose oxidation and oxygen extraction in gray matter of normal human brain: No evidence of regional differences of aerobic glycolysis.

    Science.gov (United States)

    Hyder, Fahmeed; Herman, Peter; Bailey, Christopher J; Møller, Arne; Globinsky, Ronen; Fulbright, Robert K; Rothman, Douglas L; Gjedde, Albert

    2016-05-01

    Regionally variable rates of aerobic glycolysis in brain networks identified by resting-state functional magnetic resonance imaging (R-fMRI) imply regionally variable adenosine triphosphate (ATP) regeneration. When regional glucose utilization is not matched to oxygen delivery, affected regions have correspondingly variable rates of ATP and lactate production. We tested the extent to which aerobic glycolysis and oxidative phosphorylation power R-fMRI networks by measuring quantitative differences between the oxygen to glucose index (OGI) and the oxygen extraction fraction (OEF) as measured by positron emission tomography (PET) in normal human brain (resting awake, eyes closed). Regionally uniform and correlated OEF and OGI estimates prevailed, with network values that matched the gray matter means, regardless of size, location, and origin. The spatial agreement between oxygen delivery (OEF≈0.4) and glucose oxidation (OGI ≈ 5.3) suggests that no specific regions have preferentially high aerobic glycolysis and low oxidative phosphorylation rates, with globally optimal maximum ATP turnover rates (VATP ≈ 9.4 µmol/g/min), in good agreement with (31)P and (13)C magnetic resonance spectroscopy measurements. These results imply that the intrinsic network activity in healthy human brain powers the entire gray matter with ubiquitously high rates of glucose oxidation. Reports of departures from normal brain-wide homogeny of oxygen extraction fraction and oxygen to glucose index may be due to normalization artefacts from relative PET measurements. © The Author(s) 2016.

  4. In vivo changes in microglial activation and amyloid deposits in brain regions with hypometabolism in Alzheimer's disease

    International Nuclear Information System (INIS)

    Yokokura, Masamichi; Mori, Norio; Yoshihara, Yujiro; Wakuda, Tomoyasu; Takebayashi, Kiyokazu; Iwata, Yasuhide; Nakamura, Kazuhiko; Yagi, Shunsuke; Ouchi, Yasuomi; Yoshikawa, Etsuji; Kikuchi, Mitsuru; Sugihara, Genichi; Suda, Shiro; Tsuchiya, Kenji J.; Suzuki, Katsuaki; Ueki, Takatoshi

    2011-01-01

    Amyloid β protein (Aβ) is known as a pathological substance in Alzheimer's disease (AD) and is assumed to coexist with a degree of activated microglia in the brain. However, it remains unclear whether these two events occur in parallel with characteristic hypometabolism in AD in vivo. The purpose of the present study was to clarify the in vivo relationship between Aβ accumulation and neuroinflammation in those specific brain regions in early AD. Eleven nootropic drug-naive AD patients underwent a series of positron emission tomography (PET) measurements with [ 11 C](R)PK11195, [ 11 C]PIB and [ 18 F]FDG and a battery of cognitive tests within the same day. The binding potentials (BPs) of [ 11 C](R)PK11195 were directly compared with those of [ 11 C]PIB in the brain regions with reduced glucose metabolism. BPs of [ 11 C](R)PK11195 and [ 11 C]PIB were significantly higher in the parietotemporal regions of AD patients than in ten healthy controls. In AD patients, there was a negative correlation between dementia score and [ 11 C](R)PK11195 BPs, but not [ 11 C]PIB, in the limbic, precuneus and prefrontal regions. Direct comparisons showed a significant negative correlation between [ 11 C](R)PK11195 and [ 11 C]PIB BPs in the posterior cingulate cortex (PCC) (p 18 F]FDG uptake. A lack of coupling between microglial activation and amyloid deposits may indicate that Aβ accumulation shown by [ 11 C]PIB is not always the primary cause of microglial activation, but rather the negative correlation present in the PCC suggests that microglia can show higher activation during the production of Aβ in early AD. (orig.)

  5. Defining human death: an intersection of bioethics and metaphysics.

    Science.gov (United States)

    Manninen, Bertha Alvarez

    2009-01-01

    For many years now, bioethicists, physicians, and others in the medical field have disagreed concerning how to best define human death. Different theories range from the Harvard Criteria of Brain Death, which defines death as the cessation of all brain activity, to the Cognitive Criteria, which is based on the loss of almost all core mental properties, e.g., memory, self-consciousness, moral agency, and the capacity for reason. A middle ground is the Irreversibility Standard, which defines death as occurring when the capacity for consciousness is forever lost. Given all these different theories, how can we begin to approach solving the issue of how to define death? I propose that a necessary starting point is discussing an even more fundamental question that properly belongs in the philosophical field of metaphysics: we must first address the issue of diachronic identity over time, and the persistence conditions of personal identity. In this paper, I illustrate the interdependent relationship between this metaphysical question and questions concerning the definition of death. I also illustrate how it is necessary to antecedently attend to the metaphysical issue of defining death before addressing certain issues in medical ethics, e.g., whether it is morally permissible to euthanize patients in persistent vegetative states or procure organs from anencephalic infants.

  6. A multi-atlas based method for automated anatomical Macaca fascicularis brain MRI segmentation and PET kinetic extraction.

    Science.gov (United States)

    Ballanger, Bénédicte; Tremblay, Léon; Sgambato-Faure, Véronique; Beaudoin-Gobert, Maude; Lavenne, Franck; Le Bars, Didier; Costes, Nicolas

    2013-08-15

    MRI templates and digital atlases are needed for automated and reproducible quantitative analysis of non-human primate PET studies. Segmenting brain images via multiple atlases outperforms single-atlas labelling in humans. We present a set of atlases manually delineated on brain MRI scans of the monkey Macaca fascicularis. We use this multi-atlas dataset to evaluate two automated methods in terms of accuracy, robustness and reliability in segmenting brain structures on MRI and extracting regional PET measures. Twelve individual Macaca fascicularis high-resolution 3DT1 MR images were acquired. Four individual atlases were created by manually drawing 42 anatomical structures, including cortical and sub-cortical structures, white matter regions, and ventricles. To create the MRI template, we first chose one MRI to define a reference space, and then performed a two-step iterative procedure: affine registration of individual MRIs to the reference MRI, followed by averaging of the twelve resampled MRIs. Automated segmentation in native space was obtained in two ways: 1) Maximum probability atlases were created by decision fusion of two to four individual atlases in the reference space, and transformation back into the individual native space (MAXPROB)(.) 2) One to four individual atlases were registered directly to the individual native space, and combined by decision fusion (PROPAG). Accuracy was evaluated by computing the Dice similarity index and the volume difference. The robustness and reproducibility of PET regional measurements obtained via automated segmentation was evaluated on four co-registered MRI/PET datasets, which included test-retest data. Dice indices were always over 0.7 and reached maximal values of 0.9 for PROPAG with all four individual atlases. There was no significant mean volume bias. The standard deviation of the bias decreased significantly when increasing the number of individual atlases. MAXPROB performed better when increasing the number of

  7. Brain metastasis of follicular carcinoma of the thyroid gland

    International Nuclear Information System (INIS)

    Yodonawa, Masahiko; Tanaka, Sohkichi; Kohno, Kazuyuki; Ishii, Zenichiro; Tamura, Masaru; Ohye, Chihiro.

    1987-01-01

    A 33-year-old woman had been operated on for a tumor of the thyroid gland in December of 1976, and was admitted to Saku Central Hospital in April of 1983 because of pulmonary and ovarian metastases. She underwent surgical removal of the metastatic ovarian tumor and chemotherapy, but developed headaches in June of 1983. Computed tomography (CT) scan revealed a well-defined, homogeneously enhanced mass in the right occipital region. Angiography showed a homogeneous, well-defined tumor stain supplied by the right posterior cerebral artery, the posterior branch of the middle meningeal artery, and the meningeal branch of the occipital artery. The tumor was removed in July of 1983. It was situated in the right occipital lobe and was supplied by numerous small meningeal vessels. Histologically, it was composed of small, oval-shaped cells, some with mitotic figures, and giant cells, occasionally forming a follicular structure. Three months later, the headaches reappeared, and a recurrence of brain metastasis was demonstrated by CT. In October of 1983, the second metastatic brain tumor and the dural bed were removed and local radiation therapy was administered. In this case, meningioma-like features were demonstrated by CT scan and angiography, and these findings may be characteristic of brain metastasis of follicular carcinoma of the thyroid gland. (author)

  8. Brain Connectivity and Visual Attention

    Science.gov (United States)

    Parks, Emily L.

    2013-01-01

    Abstract Emerging hypotheses suggest that efficient cognitive functioning requires the integration of separate, but interconnected cortical networks in the brain. Although task-related measures of brain activity suggest that a frontoparietal network is associated with the control of attention, little is known regarding how components within this distributed network act together or with other networks to achieve various attentional functions. This review considers both functional and structural studies of brain connectivity, as complemented by behavioral and task-related neuroimaging data. These studies show converging results: The frontal and parietal cortical regions are active together, over time, and identifiable frontoparietal networks are active in relation to specific task demands. However, the spontaneous, low-frequency fluctuations of brain activity that occur in the resting state, without specific task demands, also exhibit patterns of connectivity that closely resemble the task-related, frontoparietal attention networks. Both task-related and resting-state networks exhibit consistent relations to behavioral measures of attention. Further, anatomical structure, particularly white matter pathways as defined by diffusion tensor imaging, places constraints on intrinsic functional connectivity. Lastly, connectivity analyses applied to investigate cognitive differences across individuals in both healthy and diseased states suggest that disconnection of attentional networks is linked to deficits in cognitive functioning, and in extreme cases, to disorders of attention. Thus, comprehensive theories of visual attention and their clinical translation depend on the continued integration of behavioral, task-related neuroimaging, and brain connectivity measures. PMID:23597177

  9. Multiscale energy reallocation during low-frequency steady-state brain response.

    Science.gov (United States)

    Wang, Yifeng; Chen, Wang; Ye, Liangkai; Biswal, Bharat B; Yang, Xuezhi; Zou, Qijun; Yang, Pu; Yang, Qi; Wang, Xinqi; Cui, Qian; Duan, Xujun; Liao, Wei; Chen, Huafu

    2018-05-01

    Traditional task-evoked brain activations are based on detection and estimation of signal change from the mean signal. By contrast, the low-frequency steady-state brain response (lfSSBR) reflects frequency-tagging activity at the fundamental frequency of the task presentation and its harmonics. Compared to the activity at these resonant frequencies, brain responses at nonresonant frequencies are largely unknown. Additionally, because the lfSSBR is defined by power change, we hypothesize using Parseval's theorem that the power change reflects brain signal variability rather than the change of mean signal. Using a face recognition task, we observed power increase at the fundamental frequency (0.05 Hz) and two harmonics (0.1 and 0.15 Hz) and power decrease within the infra-slow frequency band ( .955) of their spatial distribution and brain-behavior relationship at all frequency bands. Additionally, the reallocation of finite energy was observed across various brain regions and frequency bands, forming a particular spatiotemporal pattern. Overall, results from this study strongly suggest that frequency-specific power and variability may measure the same underlying brain activity and that these results may shed light on different mechanisms between lfSSBR and brain activation, and spatiotemporal characteristics of energy reallocation induced by cognitive tasks. © 2018 Wiley Periodicals, Inc.

  10. Glutamatergic and GABAergic TCA cycle and neurotransmitter cycling fluxes in different regions of mouse brain.

    Science.gov (United States)

    Tiwari, Vivek; Ambadipudi, Susmitha; Patel, Anant B

    2013-10-01

    The (13)C nuclear magnetic resonance (NMR) studies together with the infusion of (13)C-labeled substrates in rats and humans have provided important insight into brain energy metabolism. In the present study, we have extended a three-compartment metabolic model in mouse to investigate glutamatergic and GABAergic tricarboxylic acid (TCA) cycle and neurotransmitter cycle fluxes across different regions of the brain. The (13)C turnover of amino acids from [1,6-(13)C2]glucose was monitored ex vivo using (1)H-[(13)C]-NMR spectroscopy. The astroglial glutamate pool size, one of the important parameters of the model, was estimated by a short infusion of [2-(13)C]acetate. The ratio Vcyc/VTCA was calculated from the steady-state acetate experiment. The (13)C turnover curves of [4-(13)C]/[3-(13)C]glutamate, [4-(13)C]glutamine, [2-(13)C]/[3-(13)C]GABA, and [3-(13)C]aspartate from [1,6-(13)C2]glucose were analyzed using a three-compartment metabolic model to estimate the rates of the TCA cycle and neurotransmitter cycle associated with glutamatergic and GABAergic neurons. The glutamatergic TCA cycle rate was found to be highest in the cerebral cortex (0.91 ± 0.05 μmol/g per minute) and least in the hippocampal region (0.64 ± 0.07 μmol/g per minute) of the mouse brain. In contrast, the GABAergic TCA cycle flux was found to be highest in the thalamus-hypothalamus (0.28 ± 0.01 μmol/g per minute) and least in the cerebral cortex (0.24 ± 0.02 μmol/g per minute). These findings indicate that the energetics of excitatory and inhibitory function is distinct across the mouse brain.

  11. Brain regions involved in ingestive behavior and related psychological constructs in people undergoing calorie restriction.

    Science.gov (United States)

    Kahathuduwa, Chanaka N; Boyd, Lori A; Davis, Tyler; O'Boyle, Michael; Binks, Martin

    2016-12-01

    Human food intake is regulated by physiological energy homeostatic mechanisms and hedonic mechanisms. These are affected by both very short-term and longer-term calorie restriction (CR). To date, there are parallel discussions in the literature that fail to integrate across these disciplines and topics. First, much of the available neuroimaging research focusses on specific functional paradigms (e.g. reward, energy homeostasis). These paradigms often fail to consider more complex and inclusive models that examine how potential brain regions of interest interact to influence ingestion. Second, the paradigms used focus primarily on short-term CR (fasting) which has limited generalizability to clinical application. Finally, the behavioral literature, while frequently examining longer-term CR and related psychological constructs in the context of weight management (e.g. hedonic restraint, 'liking', 'wanting' and food craving), fails to adequately tie these phenomena to underlying neural mechanisms. The result is a less than complete picture of the brain's role in the complexity of the human experience of ingestion. This disconnect highlights a major limitation in the CR literature, where attempts are persistently made to exert behavioral control over ingestion, without fully understanding the complex bio behavioral systems involved. In this review we attempt to summarize all potential brain regions important for human ingestion, present a broad conceptual overview of the brain's multifaceted role in ingestive behavior, the human (psychological) experiences related to ingestion and to examine how these factors differ according to three forms of CR. These include short-term fasting, extended CR, and restrained eating. We aim to bring together the neuroimaging literature with the behavioral literature within a conceptual framework that may inform future translational research. Copyright © 2016 The Authors. Published by Elsevier Ltd.. All rights reserved.

  12. Arteriolosclerosis that affects multiple brain regions is linked to hippocampal sclerosis of ageing

    Science.gov (United States)

    Neltner, Janna H.; Abner, Erin L.; Baker, Steven; Schmitt, Frederick A.; Kryscio, Richard J.; Jicha, Gregory A.; Smith, Charles D.; Hammack, Eleanor; Kukull, Walter A.; Brenowitz, Willa D.; Van Eldik, Linda J.

    2014-01-01

    Hippocampal sclerosis of ageing is a prevalent brain disease that afflicts older persons and has been linked with cerebrovascular pathology. Arteriolosclerosis is a subtype of cerebrovascular pathology characterized by concentrically thickened arterioles. Here we report data from multiple large autopsy series (University of Kentucky Alzheimer’s Disease Centre, Nun Study, and National Alzheimer’s Coordinating Centre) showing a specific association between hippocampal sclerosis of ageing pathology and arteriolosclerosis. The present analyses incorporate 226 cases of autopsy-proven hippocampal sclerosis of ageing and 1792 controls. Case–control comparisons were performed including digital pathological assessments for detailed analyses of blood vessel morphology. We found no evidence of associations between hippocampal sclerosis of ageing pathology and lacunar infarcts, large infarcts, Circle of Willis atherosclerosis, or cerebral amyloid angiopathy. Individuals with hippocampal sclerosis of ageing pathology did not show increased rates of clinically documented hypertension, diabetes, or other cardiac risk factors. The correlation between arteriolosclerosis and hippocampal sclerosis of ageing pathology was strong in multiple brain regions outside of the hippocampus. For example, the presence of arteriolosclerosis in the frontal cortex (Brodmann area 9) was strongly associated with hippocampal sclerosis of ageing pathology (P ageing (n = 15) and control (n = 42) cases. Following technical studies to optimize immunostaining methods for small blood vessel visualization, our analyses focused on sections immunostained for smooth muscle actin (a marker of arterioles) and CD34 (an endothelial marker), with separate analyses on grey and white matter. A total of 43 834 smooth muscle actin-positive vascular profiles and 603 798 CD34-positive vascular profiles were evaluated. In frontal cortex of cases with hippocampal sclerosis of ageing, smooth muscle actin

  13. Brain imaging in psychiatry

    International Nuclear Information System (INIS)

    Morihisa, J.M.

    1984-01-01

    This book contains the following five chapters: Positron Emission Tomography (PET) in Psychiatry; Regional Cerebral Blood Flow (CBF) in Psychiatry: Methodological Issues; Regional Cerebral Blood Flow in Psychiatry: Application to Clinical Research; Regional Cerebral Blood Flow in Psychiatry: The Resting and Activated Brains of Schizophrenic Patients; and Brain Electrical Activity Mapping (BEAM) in Psychiatry

  14. Min-max Extrapolation Scheme for Fast Estimation of 3D Potts Field Partition Functions. Application to the Joint Detection-Estimation of Brain Activity in fMRI

    International Nuclear Information System (INIS)

    Risser, L.; Vincent, T.; Ciuciu, P.; Risser, L.; Idier, J.; Risser, L.; Forbes, F.

    2011-01-01

    In this paper, we propose a fast numerical scheme to estimate Partition Functions (PF) of symmetric Potts fields. Our strategy is first validated on 2D two-color Potts fields and then on 3D two- and three-color Potts fields. It is then applied to the joint detection-estimation of brain activity from functional Magnetic Resonance Imaging (fMRI) data, where the goal is to automatically recover activated, deactivated and inactivated brain regions and to estimate region dependent hemodynamic filters. For any brain region, a specific 3D Potts field indeed embodies the spatial correlation over the hidden states of the voxels by modeling whether they are activated, deactivated or inactive. To make spatial regularization adaptive, the PFs of the Potts fields over all brain regions are computed prior to the brain activity estimation. Our approach is first based upon a classical path-sampling method to approximate a small subset of reference PFs corresponding to pre-specified regions. Then, we propose an extrapolation method that allows us to approximate the PFs associated to the Potts fields defined over the remaining brain regions. In comparison with preexisting methods either based on a path sampling strategy or mean-field approximations, our contribution strongly alleviates the computational cost and makes spatially adaptive regularization of whole brain fMRI datasets feasible. It is also robust against grid inhomogeneities and efficient irrespective of the topological configurations of the brain regions. (authors)

  15. Tinnitus alters resting state functional connectivity (RSFC) in human auditory and non-auditory brain regions as measured by functional near-infrared spectroscopy (fNIRS).

    Science.gov (United States)

    San Juan, Juan; Hu, Xiao-Su; Issa, Mohamad; Bisconti, Silvia; Kovelman, Ioulia; Kileny, Paul; Basura, Gregory

    2017-01-01

    Tinnitus, or phantom sound perception, leads to increased spontaneous neural firing rates and enhanced synchrony in central auditory circuits in animal models. These putative physiologic correlates of tinnitus to date have not been well translated in the brain of the human tinnitus sufferer. Using functional near-infrared spectroscopy (fNIRS) we recently showed that tinnitus in humans leads to maintained hemodynamic activity in auditory and adjacent, non-auditory cortices. Here we used fNIRS technology to investigate changes in resting state functional connectivity between human auditory and non-auditory brain regions in normal-hearing, bilateral subjective tinnitus and controls before and after auditory stimulation. Hemodynamic activity was monitored over the region of interest (primary auditory cortex) and non-region of interest (adjacent non-auditory cortices) and functional brain connectivity was measured during a 60-second baseline/period of silence before and after a passive auditory challenge consisting of alternating pure tones (750 and 8000Hz), broadband noise and silence. Functional connectivity was measured between all channel-pairs. Prior to stimulation, connectivity of the region of interest to the temporal and fronto-temporal region was decreased in tinnitus participants compared to controls. Overall, connectivity in tinnitus was differentially altered as compared to controls following sound stimulation. Enhanced connectivity was seen in both auditory and non-auditory regions in the tinnitus brain, while controls showed a decrease in connectivity following sound stimulation. In tinnitus, the strength of connectivity was increased between auditory cortex and fronto-temporal, fronto-parietal, temporal, occipito-temporal and occipital cortices. Together these data suggest that central auditory and non-auditory brain regions are modified in tinnitus and that resting functional connectivity measured by fNIRS technology may contribute to conscious phantom

  16. Tinnitus alters resting state functional connectivity (RSFC in human auditory and non-auditory brain regions as measured by functional near-infrared spectroscopy (fNIRS.

    Directory of Open Access Journals (Sweden)

    Juan San Juan

    Full Text Available Tinnitus, or phantom sound perception, leads to increased spontaneous neural firing rates and enhanced synchrony in central auditory circuits in animal models. These putative physiologic correlates of tinnitus to date have not been well translated in the brain of the human tinnitus sufferer. Using functional near-infrared spectroscopy (fNIRS we recently showed that tinnitus in humans leads to maintained hemodynamic activity in auditory and adjacent, non-auditory cortices. Here we used fNIRS technology to investigate changes in resting state functional connectivity between human auditory and non-auditory brain regions in normal-hearing, bilateral subjective tinnitus and controls before and after auditory stimulation. Hemodynamic activity was monitored over the region of interest (primary auditory cortex and non-region of interest (adjacent non-auditory cortices and functional brain connectivity was measured during a 60-second baseline/period of silence before and after a passive auditory challenge consisting of alternating pure tones (750 and 8000Hz, broadband noise and silence. Functional connectivity was measured between all channel-pairs. Prior to stimulation, connectivity of the region of interest to the temporal and fronto-temporal region was decreased in tinnitus participants compared to controls. Overall, connectivity in tinnitus was differentially altered as compared to controls following sound stimulation. Enhanced connectivity was seen in both auditory and non-auditory regions in the tinnitus brain, while controls showed a decrease in connectivity following sound stimulation. In tinnitus, the strength of connectivity was increased between auditory cortex and fronto-temporal, fronto-parietal, temporal, occipito-temporal and occipital cortices. Together these data suggest that central auditory and non-auditory brain regions are modified in tinnitus and that resting functional connectivity measured by fNIRS technology may contribute to

  17. A regional chemostratigraphically-defined correlation framework for the late Triassic TAG-I Formation in Blocks 402 and 405a, Algeria

    Energy Technology Data Exchange (ETDEWEB)

    Ratcliffe, K.T.; Martin, J.; Pearce, T.J. [Chemostrat ltd., Llanfyllin, Powys (United Kingdom); Hughes, A.D. [Bington Resources, London (United Kingdom); Lawton, D.E. [BHP Billiton Petroleum Ltd., London (United Kingdom); Wray, D. [University of Greenwich, Chatham Maritime (United Kingdom). Department of Earth Sciences; Bessa, F. [Sonatrach, Hydra (Algeria). Division Petroleum Engineering and Development

    2006-07-01

    The Triassic Argilo-Greseux Inferieur Formation (TAG-I) is one of the principal hydrocarbon reservoirs in the Berkine Basin of Algeria. Sedimentological studies have shown that it exhibits marked spatial and temporal facies variations on both a local field scale and a regional basinal scale. This variability, combined with a lack of diagnostic flora and fauna, makes regional correlation within the unit difficult. In turn, the lack of a consistent regional stratigraphic framework hampers the comparison of the various correlation schemes devised by operators in the basin. Contrasting the TAG-I in Blocks 402 and 405a exemplifies the problems encountered when attempting regionally to define a correlation framework for the interval. Between these two blocks, a distance of approximately 200 km, there are marked changes in the style of deposition from sand-dominated, proximal fluvial systems in the SW (Block 405a, MLN, MLC, KMD and MLNW fields) to a more distal, more clay-prone system in the NE (Block 402, ROD/BRSE/BSFN, SFNE and BSF fields). A chemostratigraphic study of the TAG-I in these clocks has allowed a four-fold correlation framework to be defined, where each chemostratigraphic package has distinctive geochemical features. Chemostratigraphic Package 10, the oldest unit, lies above the Hercynian Unconformity, but beneath a geochemically identifiable hiatal surface. Chemostratigraphic Package 20 lies above the hiatal surface but is separated from the overlying packages by a mineralogical change identifiable in both claystone and sandstone geochemistry. Chemostratigraphic Packages 30 and 40 are chemically somewhat similar, but are separated by a regional event interpreted as a period of dolocrete and lacustrine development. By combining the geochemical differentiation of the units and recognition of their stratal boundaries, it is possible to define a correlation for the TAG-I between Blocks 402 and 405a. The proposed correlation between the two blocks suggests that

  18. Rapid intranasal delivery of chloramphenicol acetyltransferase in the active form to different brain regions as a model for enzyme therapy in the CNS.

    Science.gov (United States)

    Appu, Abhilash P; Arun, Peethambaran; Krishnan, Jishnu K S; Moffett, John R; Namboodiri, Aryan M A

    2016-02-01

    The blood brain barrier (BBB) is critical for maintaining central nervous system (CNS) homeostasis by restricting entry of potentially toxic substances. However, the BBB is a major obstacle in the treatment of neurotoxicity and neurological disorders due to the restrictive nature of the barrier to many medications. Intranasal delivery of active enzymes to the brain has therapeutic potential for the treatment of numerous CNS enzyme deficiency disorders and CNS toxicity caused by chemical threat agents. The aim of this work is to provide a sensitive model system for analyzing the rapid delivery of active enzymes into various regions of the brain with therapeutic bioavailability. We tested intranasal delivery of chloramphenicol acetyltransferase (CAT), a relatively large (75kD) enzyme, in its active form into different regions of the brain. CAT was delivered intranasally to anaesthetized rats and enzyme activity was measured in different regions using a highly specific High Performance Thin Layer Chromatography (HP-TLC)-radiometry coupled assay. Active enzyme reached all examined areas of the brain within 15min (the earliest time point tested). In addition, the yield of enzyme activity in the brain was almost doubled in the brains of rats pre-treated with matrix metalloproteinase-9 (MMP-9). Intranasal administration of active enzymes in conjunction with MMP-9 to the CNS is both rapid and effective. The present results suggest that intranasal enzyme therapy is a promising method for counteracting CNS chemical threat poisoning, as well as for treating CNS enzyme deficiency disorders. Published by Elsevier B.V.

  19. Variations and asymmetries in regional brain surface in the genus Homo.

    Science.gov (United States)

    Balzeau, Antoine; Holloway, Ralph L; Grimaud-Hervé, Dominique

    2012-06-01

    Paleoneurology is an important field of research within human evolution studies. Variations in size and shape of an endocast help to differentiate among fossil hominin species whereas endocranial asymmetries are related to behavior and cognitive function. Here we analyse variations of the surface of the frontal, parieto-temporal and occipital lobes among different species of Homo, including 39 fossil hominins, ten fossil anatomically modern Homo sapiens and 100 endocasts of extant modern humans. We also test for the possible asymmetries of these features in a large sample of modern humans and observe individual particularities in the fossil specimens. This study contributes important new information about the brain evolution in the genus Homo. Our results show that the general pattern of surface asymmetry for the different regional brain surfaces in fossil species of Homo does not seem to be different from the pattern described in a large sample of anatomically modern H. sapiens, i.e., the right hemisphere has a larger surface than the left, as do the right frontal, the right parieto-temporal and the left occipital lobes compared with the contra-lateral side. It also appears that Asian Homo erectus specimens are discriminated from all other samples of Homo, including African and Georgian specimens that are also sometimes included in that taxon. The Asian fossils show a significantly smaller relative size of the parietal and temporal lobes. Neandertals and anatomically modern H. sapiens, who share the largest endocranial volume of all hominins, show differences when considering the relative contribution of the frontal, parieto-temporal and occipital lobes. These results illustrate an original variation in the pattern of brain organization in hominins independent of variations in total size. The globularization of the brain and the enlargement of the parietal lobes could be considered derived features observed uniquely in anatomically modern H. sapiens. Copyright

  20. Thermodynamic laws apply to brain function.

    Science.gov (United States)

    Salerian, Alen J

    2010-02-01

    Thermodynamic laws and complex system dynamics govern brain function. Thus, any change in brain homeostasis by an alteration in brain temperature, neurotransmission or content may cause region-specific brain dysfunction. This is the premise for the Salerian Theory of Brain built upon a new paradigm for neuropsychiatric disorders: the governing influence of neuroanatomy, neurophysiology, thermodynamic laws. The principles of region-specific brain function thermodynamics are reviewed. The clinical and supporting evidence including the paradoxical effects of various agents that alter brain homeostasis is demonstrated.

  1. (+)- and (-)-N-allylnormetazocine binding sites in mouse brain: in vitro and in vivo characterization and regional distribution

    International Nuclear Information System (INIS)

    Compton, D.R.; Bagley, R.B.; Katzen, J.S.; Martin, B.R.

    1987-01-01

    In vivo and in vitro binding studies, both in whole brain and in selected areas, indicate that non-identical (+)- and (-)-NANM sites exist in the mouse brain, and each exhibits a different regional distribution. The in vivo binding of (+)- 3 H-NANM was found to be saturable at pharmacologically relevant doses, and represents a relatively small (10 - 22%) portion of total brain (+)- 3 H-NANM concentrations. The in vivo binding of (+)- 3 H-NANM was selectively displaced by (+)-NANM and PCP, and more sensitive to haloperidol and (+)-ketocyclazocine than the (-)- 3 H-NANM site. The in vivo binding of (-)- 3 H-NANM was selectively displaced by (-)-NANM, and more sensitive to naloxone and (-) ketocyclazocine than the (+)- 3 H-NANM site, and insensitive to PCP. This study indicates that the investigation of NANM binding sites is possible using in vivo binding techniques, and that each isomer apparently binds, in the mouse brain, to a single class of distinct sites. 32 references, 4 figures, 2 tables

  2. Zebrafish homologs of genes within 16p11.2, a genomic region associated with brain disorders, are active during brain development, and include two deletion dosage sensor genes

    Directory of Open Access Journals (Sweden)

    Alicia Blaker-Lee

    2012-11-01

    Deletion or duplication of one copy of the human 16p11.2 interval is tightly associated with impaired brain function, including autism spectrum disorders (ASDs, intellectual disability disorder (IDD and other phenotypes, indicating the importance of gene dosage in this copy number variant region (CNV. The core of this CNV includes 25 genes; however, the number of genes that contribute to these phenotypes is not known. Furthermore, genes whose functional levels change with deletion or duplication (termed ‘dosage sensors’, which can associate the CNV with pathologies, have not been identified in this region. Using the zebrafish as a tool, a set of 16p11.2 homologs was identified, primarily on chromosomes 3 and 12. Use of 11 phenotypic assays, spanning the first 5 days of development, demonstrated that this set of genes is highly active, such that 21 out of the 22 homologs tested showed loss-of-function phenotypes. Most genes in this region were required for nervous system development – impacting brain morphology, eye development, axonal density or organization, and motor response. In general, human genes were able to substitute for the fish homolog, demonstrating orthology and suggesting conserved molecular pathways. In a screen for 16p11.2 genes whose function is sensitive to hemizygosity, the aldolase a (aldoaa and kinesin family member 22 (kif22 genes were identified as giving clear phenotypes when RNA levels were reduced by ∼50%, suggesting that these genes are deletion dosage sensors. This study leads to two major findings. The first is that the 16p11.2 region comprises a highly active set of genes, which could present a large genetic target and might explain why multiple brain function, and other, phenotypes are associated with this interval. The second major finding is that there are (at least two genes with deletion dosage sensor properties among the 16p11.2 set, and these could link this CNV to brain disorders such as ASD and IDD.

  3. Asymmetry of the structural brain connectome in healthy older adults.

    Directory of Open Access Journals (Sweden)

    Leonardo eBonilha

    2014-01-01

    Full Text Available Background: It is now possible to map neural connections in vivo across the whole brain (i.e., the brain connectome. This is a promising development in neuroscience since many health and disease processes are believed to arise from the architecture of neural networks.Objective: To describe the normal range of hemispheric asymmetry in structural connectivity in healthy older adults.Methods: We obtained high-resolution structural magnetic resonance images (MRI from 17 healthy older adults. For each subject, the brain connectome was reconstructed by parcelating the probabilistic map of gray matter into anatomically defined regions of interested (ROIs. White matter fiber tractography was reconstructed from diffusion tensor imaging and streamlines connecting gray matter ROIs were computed. Asymmetry indices were calculated regarding ROI connectivity (representing the sum of connectivity weight of each cortical ROI and for regional white matter links. All asymmetry measures were compared to a normal distribution with mean=0 through one sample t-tests.Results: Leftward cortical ROI asymmetry was observed in medial temporal, dorsolateral frontal and occipital regions. Rightward cortical ROI asymmetry was observed in middle temporal and orbito-frontal regions. Link-wise asymmetry revealed stronger connections in the left hemisphere between the medial temporal, anterior and posterior peri-Sylvian and occipito-temporal regions. Rightward link asymmetry was observed in lateral temporal, parietal and dorsolateral frontal connections.Conclusions: We postulate that asymmetry of specific connections may be related to functional hemispheric organization. This study may provide reference for future studies evaluating the architecture of the connectome in health and disease processes in senior individuals.

  4. Parcellation of the Healthy Neonatal Brain into 107 Regions Using Atlas Propagation through Intermediate Time Points in Childhood.

    Science.gov (United States)

    Blesa, Manuel; Serag, Ahmed; Wilkinson, Alastair G; Anblagan, Devasuda; Telford, Emma J; Pataky, Rozalia; Sparrow, Sarah A; Macnaught, Gillian; Semple, Scott I; Bastin, Mark E; Boardman, James P

    2016-01-01

    Neuroimage analysis pipelines rely on parcellated atlases generated from healthy individuals to provide anatomic context to structural and diffusion MRI data. Atlases constructed using adult data introduce bias into studies of early brain development. We aimed to create a neonatal brain atlas of healthy subjects that can be applied to multi-modal MRI data. Structural and diffusion 3T MRI scans were acquired soon after birth from 33 typically developing neonates born at term (mean postmenstrual age at birth 39(+5) weeks, range 37(+2)-41(+6)). An adult brain atlas (SRI24/TZO) was propagated to the neonatal data using temporal registration via childhood templates with dense temporal samples (NIH Pediatric Database), with the final atlas (Edinburgh Neonatal Atlas, ENA33) constructed using the Symmetric Group Normalization (SyGN) method. After this step, the computed final transformations were applied to T2-weighted data, and fractional anisotropy, mean diffusivity, and tissue segmentations to provide a multi-modal atlas with 107 anatomical regions; a symmetric version was also created to facilitate studies of laterality. Volumes of each region of interest were measured to provide reference data from normal subjects. Because this atlas is generated from step-wise propagation of adult labels through intermediate time points in childhood, it may serve as a useful starting point for modeling brain growth during development.

  5. Parcellation of the healthy neonatal brain into 107 regions using atlas propagation through intermediate time points in childhood

    Directory of Open Access Journals (Sweden)

    Manuel eBlesa Cabez

    2016-05-01

    Full Text Available Neuroimage analysis pipelines rely on parcellated atlases generated from healthy individuals to provide anatomic context to structural and diffusion MRI data. Atlases constructed using adult data introduce bias into studies of early brain development. We aimed to create a neonatal brain atlas of healthy subjects that can be applied to multi-modal MRI data. Structural and diffusion 3T MRI scans were acquired soon after birth from 33 typically developing neonates born at term (mean postmenstrual age at birth 39+5 weeks, range 37+2-41+6. An adult brain atlas (SRI24/TZO was propagated to the neonatal data using temporal registration via childhood templates with dense temporal samples (NIH Pediatric Database, with the final atlas (Edinburgh Neonatal Atlas, ENA33 constructed using the Symmetric Group Normalization method. After this step, the computed final transformations were applied to T2-weighted data, and fractional anisotropy, mean diffusivity, and tissue segmentations to provide a multi-modal atlas with 107 anatomical regions; a symmetric version was also created to facilitate studies of laterality. Volumes of each region of interest were measured to provide reference data from normal subjects. Because this atlas is generated from step-wise propagation of adult labels through intermediate time points in childhood, it may serve as a useful starting point for modelling brain growth during development.

  6. Radiopharmaceuticals for the imaging of functional abnormalities of the developing brain

    International Nuclear Information System (INIS)

    Senekowitsch, R.; Kriegel, H.

    1986-01-01

    The measurement of physiological parameters in man is possible with the help of positron emission tomography (PET) and radiopharmaceuticals labeled with short lived positron emitters as C 11, N 13, O 15 and F 18. With the use of this substances it is possible to make a tomographic map defining regional metabolic parameters in normal and diseased brain. This technique has therefore also be named 'in vivo autoradiography'. The possibility of applying C 11 or F 18 labeled deoxyglucose with PET for detecting regional and local changes in cerebral metabolic rate of glucose in brain development in children of 5 days to 1 year of age is discussed. Beyond this a relationship between cerebral metabolic rate of glucose, cerebral blood flow and cerebral metabolic rate of oxygen by use of this technique after inhalation of O 15 and C 11-labeled CO 2 is shown. Attention is drawn to the application of C 11-methyl-spiperone and PET to visualize dopamine receptor density in the brain. The receptor density and the ability of receptors to bind neutrotransmitters is found to be influenced by prenatal irradiation. It is expected that relations between alterations in the developing brain and its postnatal function may be explored in this way. (orig.)

  7. Regional brain activity during early-stage intense romantic love predicted relationship outcomes after 40 months: an fMRI assessment.

    Science.gov (United States)

    Xu, Xiaomeng; Brown, Lucy; Aron, Arthur; Cao, Guikang; Feng, Tingyong; Acevedo, Bianca; Weng, Xuchu

    2012-09-20

    Early-stage romantic love is associated with activation in reward and motivation systems of the brain. Can these localized activations, or others, predict long-term relationship stability? We contacted participants from a previous fMRI study of early-stage love by Xu et al. [34] after 40 months from initial assessments. We compared brain activation during the initial assessment at early-stage love for those who were still together at 40 months and those who were apart, and surveyed those still together about their relationship happiness and commitment at 40 months. Six participants who were still with their partners at 40 months (compared to six who had broken up) showed less activation during early-stage love in the medial orbitofrontal cortex, right subcallosal cingulate and right accumbens, regions implicated in long-term love and relationship satisfaction [1,2]. These regions of deactivation at the early stage of love were also negatively correlated with relationship happiness scores collected at 40 months. Other areas involved were the caudate tail, and temporal and parietal lobes. These data are preliminary evidence that neural responses in the early stages of romantic love can predict relationship stability and quality up to 40 months later in the relationship. The brain regions involved suggest that forebrain reward functions may be predictive for relationship stability, as well as regions involved in social evaluation, emotional regulation, and mood. Copyright © 2012 Elsevier Ireland Ltd. All rights reserved.

  8. Semiautomated volumetry of the cerebrum, cerebellum-brain stem, and temporal lobe on brain magnetic resonance images

    International Nuclear Information System (INIS)

    Hayashi, Norio; Matsuura, Yukihiro; Kawahara, Kazuhiro; Tsujii, Hideo; Yamamoto, Tomoyuki; Sanada, Shigeru; Suzuki, Masayuki; Matsui, Osamu

    2008-01-01

    The aim of this study was to develop an automated method of segmenting the cerebrum, cerebellum-brain stem, and temporal lobe simultaneously on magnetic resonance (MR) images. We obtained T1-weighted MR images from 10 normal subjects and 19 patients with brain atrophy. To perform automated volumetry from MR images, we performed the following three steps: segmentation of the brain region; separation between the cerebrum and the cerebellum-brain stem; and segmentation of the temporal lobe. Evaluation was based on the correctly recognized region (CRR) (i.e., the region recognized by both the automated and manual methods). The mean CRRs of the normal and atrophic brains were 98.2% and 97.9% for the cerebrum, 87.9% and 88.5% for the cerebellum-brain stem, and 76.9% and 85.8% for the temporal lobe, respectively. We introduce an automated volumetric method for the cerebrum, cerebellum-brain stem, and temporal lobe on brain MR images. Our method can be applied to not only the normal brain but also the atrophic brain. (author)

  9. Bacterial lipopolysaccharide-induced systemic inflammation alters perfusion of white matter-rich regions without altering flow in brain-irrigating arteries: Relationship to blood-brain barrier breakdown?

    Science.gov (United States)

    Dhaya, Ibtihel; Griton, Marion; Raffard, Gérard; Amri, Mohamed; Hiba, Bassem; Konsman, Jan Pieter

    2018-01-15

    To better understand brain dysfunction during sepsis, cerebral arterial blood flow was assessed with Phase Contrast Magnetic Resonance Imaging, perfusion with Arterial Spin Labeling and structure with diffusion-weighted Magnetic Resonance Imaging in rats after intraperitoneal administration of bacterial lipopolysaccharides. Although cerebral arterial flow was not altered, perfusion of the corpus callosum region and diffusion parallel to its fibers were higher after lipopolysaccharide administration as compared to saline injection. In parallel, lipopolysaccharide induced perivascular immunoglobulin-immunoreactivity in white matter. These findings indicate that systemic inflammation can result in increased perfusion, blood-brain barrier breakdown and altered water diffusion in white matter. Copyright © 2017 Elsevier B.V. All rights reserved.

  10. Algorithm to find high density EEG scalp coordinates and analysis of their correspondence to structural and functional regions of the brain.

    Science.gov (United States)

    Giacometti, Paolo; Perdue, Katherine L; Diamond, Solomon G

    2014-05-30

    Interpretation and analysis of electroencephalography (EEG) measurements relies on the correspondence of electrode scalp coordinates to structural and functional regions of the brain. An algorithm is introduced for automatic calculation of the International 10-20, 10-10, and 10-5 scalp coordinates of EEG electrodes on a boundary element mesh of a human head. The EEG electrode positions are then used to generate parcellation regions of the cerebral cortex based on proximity to the EEG electrodes. The scalp electrode calculation method presented in this study effectively and efficiently identifies EEG locations without prior digitization of coordinates. The average of electrode proximity parcellations of the cortex were tabulated with respect to structural and functional regions of the brain in a population of 20 adult subjects. Parcellations based on electrode proximity and EEG sensitivity were compared. The parcellation regions based on sensitivity and proximity were found to have 44.0 ± 11.3% agreement when demarcated by the International 10-20, 32.4 ± 12.6% by the 10-10, and 24.7 ± 16.3% by the 10-5 electrode positioning system. The EEG positioning algorithm is a fast and easy method of locating EEG scalp coordinates without the need for digitized electrode positions. The parcellation method presented summarizes the EEG scalp locations with respect to brain regions without computation of a full EEG forward model solution. The reference table of electrode proximity versus cortical regions may be used by experimenters to select electrodes that correspond to anatomical and functional regions of interest. Copyright © 2014 Elsevier B.V. All rights reserved.

  11. Histological and elemental changes in the rat brain after local irradiation with carbon ion beams

    Energy Technology Data Exchange (ETDEWEB)

    Takahashi, Sentaro; Sun, Xue-Zhi; Kubota, Yoshihisa; Takai, Nobuhiko; Nojima, Kumie [National Inst. of Radiological Sciences, Chiba (Japan)

    2002-06-01

    The left cerebral hemispheres of adult Sprague-Dawley rat brains were irradiated at doses of 30, 50, or 100 Gy with charged carbon particles (290 MeV/nucleon; 5 mm spread-out Bragg peak). The spread-out Bragg peak used here successfully and satisfactorily retained its high-dose localization in the defined region. A histological examination showed that necrotic tissue damage, hemorrhage in the thalamus, and vasodilatations around the necrotic region were induced at 8 weeks after 100 Gy irradiation. The regions with tissue damage correlated well with those expected from the radiation-dose distribution, indicating an advantage of charged carbon particles for irradiating restricted brain regions. An X-ray fluorescent analysis demonstrated a decrease in the concentrations of K and P, and an increase in the concentrations of Cl, Fe, Zn in the damaged region at 8 weeks post-irradiation, though no significant changes were observed before 4 weeks of post-irradiation. This may indicate that even the very high radiation doses used here did not induce acute and immediate neuronal cell death, in contrast with ischemic brain injury where acute neuronal cell death occurred and the elemental concentrations changed within a day after the induction of ischemia. (author)

  12. When the Brain Takes 'BOLD' Steps: Real-Time fMRI Neurofeedback Can Further Enhance the Ability to Gradually Self-regulate Regional Brain Activation.

    Science.gov (United States)

    Sorger, Bettina; Kamp, Tabea; Weiskopf, Nikolaus; Peters, Judith Caroline; Goebel, Rainer

    2018-05-15

    Brain-computer interfaces (BCIs) based on real-time functional magnetic resonance imaging (rtfMRI) are currently explored in the context of developing alternative (motor-independent) communication and control means for the severely disabled. In such BCI systems, the user encodes a particular intention (e.g., an answer to a question or an intended action) by evoking specific mental activity resulting in a distinct brain state that can be decoded from fMRI activation. One goal in this context is to increase the degrees of freedom in encoding different intentions, i.e., to allow the BCI user to choose from as many options as possible. Recently, the ability to voluntarily modulate spatial and/or temporal blood oxygenation level-dependent (BOLD)-signal features has been explored implementing different mental tasks and/or different encoding time intervals, respectively. Our two-session fMRI feasibility study systematically investigated for the first time the possibility of using magnitudinal BOLD-signal features for intention encoding. Particularly, in our novel paradigm, participants (n=10) were asked to alternately self-regulate their regional brain-activation level to 30%, 60% or 90% of their maximal capacity by applying a selected activation strategy (i.e., performing a mental task, e.g., inner speech) and modulation strategies (e.g., using different speech rates) suggested by the experimenters. In a second step, we tested the hypothesis that the additional availability of feedback information on the current BOLD-signal level within a region of interest improves the gradual-self regulation performance. Therefore, participants were provided with neurofeedback in one of the two fMRI sessions. Our results show that the majority of the participants were able to gradually self-regulate regional brain activation to at least two different target levels even in the absence of neurofeedback. When provided with continuous feedback on their current BOLD-signal level, most

  13. Multi-Scale Factor Analysis of High-Dimensional Brain Signals

    KAUST Repository

    Ting, Chee-Ming

    2017-05-18

    In this paper, we develop an approach to modeling high-dimensional networks with a large number of nodes arranged in a hierarchical and modular structure. We propose a novel multi-scale factor analysis (MSFA) model which partitions the massive spatio-temporal data defined over the complex networks into a finite set of regional clusters. To achieve further dimension reduction, we represent the signals in each cluster by a small number of latent factors. The correlation matrix for all nodes in the network are approximated by lower-dimensional sub-structures derived from the cluster-specific factors. To estimate regional connectivity between numerous nodes (within each cluster), we apply principal components analysis (PCA) to produce factors which are derived as the optimal reconstruction of the observed signals under the squared loss. Then, we estimate global connectivity (between clusters or sub-networks) based on the factors across regions using the RV-coefficient as the cross-dependence measure. This gives a reliable and computationally efficient multi-scale analysis of both regional and global dependencies of the large networks. The proposed novel approach is applied to estimate brain connectivity networks using functional magnetic resonance imaging (fMRI) data. Results on resting-state fMRI reveal interesting modular and hierarchical organization of human brain networks during rest.

  14. Dopamine D(2) receptor quantification in extrastriatal brain regions using [(123)I]epidepride with bolus/infusion

    DEFF Research Database (Denmark)

    Pinborg, L H; Videbaek, C; Knudsen, G M

    2000-01-01

    the significance of individual differences in plasma clearance and binding parameters. A steady-state condition, however, could not be attained in striatal brain regions using a B/I protocol of 20 h, even after 11 h. Under near steady-state conditions a striatal:cerebellar ratio of 23 was demonstrated. Epidepride...

  15. A Novel Histogram Region Merging Based Multithreshold Segmentation Algorithm for MR Brain Images

    Directory of Open Access Journals (Sweden)

    Siyan Liu

    2017-01-01

    Full Text Available Multithreshold segmentation algorithm is time-consuming, and the time complexity will increase exponentially with the increase of thresholds. In order to reduce the time complexity, a novel multithreshold segmentation algorithm is proposed in this paper. First, all gray levels are used as thresholds, so the histogram of the original image is divided into 256 small regions, and each region corresponds to one gray level. Then, two adjacent regions are merged in each iteration by a new designed scheme, and a threshold is removed each time. To improve the accuracy of the merger operation, variance and probability are used as energy. No matter how many the thresholds are, the time complexity of the algorithm is stable at O(L. Finally, the experiment is conducted on many MR brain images to verify the performance of the proposed algorithm. Experiment results show that our method can reduce the running time effectively and obtain segmentation results with high accuracy.

  16. Dynamic relationships between age, amyloid-β deposition, and glucose metabolism link to the regional vulnerability to Alzheimer’s disease

    Science.gov (United States)

    Madison, Cindee; Baker, Suzanne; Rabinovici, Gil; Jagust, William

    2016-01-01

    Abstract See Hansson and Gouras (doi:10.1093/aww146) for a scientific commentary on this article. Although some brain regions such as precuneus and lateral temporo-parietal cortex have been shown to be more vulnerable to Alzheimer’s disease than other areas, a mechanism underlying the differential regional vulnerability to Alzheimer’s disease remains to be elucidated. Using fluorodeoxyglucose and Pittsburgh compound B positron emission tomography imaging glucose metabolism and amyloid-β deposition, we tested whether and how life-long changes in glucose metabolism relate to amyloid-β deposition and Alzheimer’s disease-related hypometabolism. Nine healthy young adults (age range: 20–30), 96 cognitively normal older adults (age range: 61–96), and 20 patients with Alzheimer’s disease (age range: 50–90) were scanned using fluorodeoxyglucose and Pittsburgh compound B positron emission tomography. Among cognitively normal older subjects, 32 were further classified as amyloid-positive, with 64 as amyloid-negative. To assess the contribution of glucose metabolism to the regional vulnerability to amyloid-β deposition, we defined the highest and lowest metabolic regions in young adults and examined differences in amyloid deposition between these regions across groups. Two-way analyses of variance were conducted to assess regional differences in age and amyloid-β-related changes in glucose metabolism. Multiple regressions were applied to examine the association between amyloid-β deposition and regional glucose metabolism. Both region of interest and whole-brain voxelwise analyses were conducted to complement and confirm the results derived from the other approach. Regional differences in glucose metabolism between the highest and lowest metabolism regions defined in young adults (T = 12.85, P glucose metabolism regions defined in young adults (T = 2.05, P glucose metabolism were found such that frontal glucose metabolism was reduced with age, while glucose

  17. Lutein accumulates in subcellular membranes of brain regions in adult rhesus macaques: Relationship to DHA oxidation products.

    Directory of Open Access Journals (Sweden)

    Emily S Mohn

    Full Text Available Lutein, a carotenoid with anti-oxidant functions, preferentially accumulates in primate brain and is positively related to cognition in humans. Docosahexaenoic acid (DHA, an omega-3 polyunsaturated fatty acid (PUFA, is also beneficial for cognition, but is susceptible to oxidation. The present study characterized the membrane distribution of lutein in brain regions important for different domains of cognitive function and determined whether membrane lutein was associated with brain PUFA oxidation.Adult rhesus monkeys were fed a stock diet (~2 mg/day lutein or ~0.5 μmol/kg body weight/day (n = 9 or the stock diet plus a daily supplement of lutein (~4.5 mg/day or~1 μmol/kg body weight/day and zeaxanthin (~0.5 mg/day or 0.1 μmol/kg body weight/day for 6-12 months (n = 4. Nuclear, myelin, mitochondrial, and neuronal plasma membranes were isolated using a Ficoll density gradient from prefrontal cortex (PFC, cerebellum (CER, striatum (ST, and hippocampus (HC. Carotenoids, PUFAs, and PUFA oxidation products were measured using HPLC, GC, and LC-GC/MS, respectively.All-trans-lutein (ng/mg protein was detected in all regions and membranes and was highly variable among monkeys. Lutein/zeaxanthin supplementation significantly increased total concentrations of lutein in serum, PFC and CER, as well as lutein in mitochondrial membranes and total DHA concentrations in PFC only (P<0.05. In PFC and ST, mitochondrial lutein was inversely related to DHA oxidation products, but not those from arachidonic acid (P <0.05.This study provides novel data on subcellular lutein accumulation and its relationship to DHA oxidation in primate brain. These findings support the hypothesis that lutein may be associated with antioxidant functions in the brain.

  18. Examination of the regional distribution of minor and trace elements in normal human brain by PIXE and chemometric techniques

    International Nuclear Information System (INIS)

    Maenhaut, W.; Hebbrecht, G.; Reuck, J. de

    1993-01-01

    Particle-induced X-ray emission (PIXE) was used to measure two minor and six trace elements, i.e. K, Ca, Mn, Fe, Cu, Zn, Se, and Rb, in up to 50 different structures (regions) of brains from Belgian individuals without neurological disorders. The data matrix with the mean dry-weight elemental concentrations and mean wet-to-dry weight ratio (means over 18 brains) for the various structures was subjected to two chemometric techniques, i.e., VARIMAX rotated absolute principal component analysis (APCA) and hierarchical cluster analysis. Three components were identified by APCA: Components 1 and 3 represented aqueous fractions of the brain (respectively the intracellular and extracellular fluid), whereas component 2 apparently represented the solid brain fraction. The elements K, Cu, Zn, Se, and Rb were predominantly attributed to component 1, Ca to component 3, and Fe to component 2. In the hierarchical cluster analysis seven different agglomerative cluster strategies were compared. The dendrograms obtained from the furthest neighbor and Ward's error sum strategy were virtually identical, and they consisted of two large clusters with 30 and 16 structures, respectively. The first cluster included all gray matter structures, while the second comprised all white matter. Furthermore, structures involved in the same physiological function or morphologically similar regions often conglomerated in one subcluster. This strongly suggests that there is some relationship between the trace element profile of a brain structure and its function. (orig.)

  19. Analysis of Regional Cerebral Blood Flow Using {sup 99m}Tc-HMPAO Brain SPECT in Senile Dementia of Alzheimer Type

    Energy Technology Data Exchange (ETDEWEB)

    Lee, Myung Hae; Lee, Myung Chul; Koh, Chang Soon; Roh, Jae Kyu; Woo, Chong In [Seoul National University College of Medicine, Seoul (Korea, Republic of)

    1988-03-15

    {sup 99m}Tc-HMPAO brain SPECT studies were performed in 11 patients with Alzheimer's disease, 7 patients with psychological depression and 12 normal controls. Changes of regional cerebral blood flow was semiquantitatively analyzed and the results were as follows. 1) In 11 patients with Alzheimer's disease, significant reduction of regional cerebral blood flow was found In both temporoparietal areas. 2) Relative perfusion between cerebral hemispheres was rather symmetrical in patient with Alzheimer's disease. 3) All patients with depression showed normal SPECT findings. As for conclusion, {sup 99m}Tc-HMPAO brain SPECT seemed to be a valuable method for clinical assessment and management of patients with Alzheimer's disease.

  20. An extensive assessment of network alignment algorithms for comparison of brain connectomes.

    Science.gov (United States)

    Milano, Marianna; Guzzi, Pietro Hiram; Tymofieva, Olga; Xu, Duan; Hess, Christofer; Veltri, Pierangelo; Cannataro, Mario

    2017-06-06

    Recently the study of the complex system of connections in neural systems, i.e. the connectome, has gained a central role in neurosciences. The modeling and analysis of connectomes are therefore a growing area. Here we focus on the representation of connectomes by using graph theory formalisms. Macroscopic human brain connectomes are usually derived from neuroimages; the analyzed brains are co-registered in the image domain and brought to a common anatomical space. An atlas is then applied in order to define anatomically meaningful regions that will serve as the nodes of the network - this process is referred to as parcellation. The atlas-based parcellations present some known limitations in cases of early brain development and abnormal anatomy. Consequently, it has been recently proposed to perform atlas-free random brain parcellation into nodes and align brains in the network space instead of the anatomical image space, as a way to deal with the unknown correspondences of the parcels. Such process requires modeling of the brain using graph theory and the subsequent comparison of the structure of graphs. The latter step may be modeled as a network alignment (NA) problem. In this work, we first define the problem formally, then we test six existing state of the art of network aligners on diffusion MRI-derived brain networks. We compare the performances of algorithms by assessing six topological measures. We also evaluated the robustness of algorithms to alterations of the dataset. The results confirm that NA algorithms may be applied in cases of atlas-free parcellation for a fully network-driven comparison of connectomes. The analysis shows MAGNA++ is the best global alignment algorithm. The paper presented a new analysis methodology that uses network alignment for validating atlas-free parcellation brain connectomes. The methodology has been experimented on several brain datasets.

  1. Altered structural connectivity of pain-related brain network in burning mouth syndrome-investigation by graph analysis of probabilistic tractography.

    Science.gov (United States)

    Wada, Akihiko; Shizukuishi, Takashi; Kikuta, Junko; Yamada, Haruyasu; Watanabe, Yusuke; Imamura, Yoshiki; Shinozaki, Takahiro; Dezawa, Ko; Haradome, Hiroki; Abe, Osamu

    2017-05-01

    Burning mouth syndrome (BMS) is a chronic intraoral pain syndrome featuring idiopathic oral pain and burning discomfort despite clinically normal oral mucosa. The etiology of chronic pain syndrome is unclear, but preliminary neuroimaging research has suggested the alteration of volume, metabolism, blood flow, and diffusion at multiple brain regions. According to the neuromatrix theory of Melzack, pain sense is generated in the brain by the network of multiple pain-related brain regions. Therefore, the alteration of pain-related network is also assumed as an etiology of chronic pain. In this study, we investigated the brain network of BMS brain by using probabilistic tractography and graph analysis. Fourteen BMS patients and 14 age-matched healthy controls underwent 1.5T MRI. Structural connectivity was calculated in 83 anatomically defined regions with probabilistic tractography of 60-axis diffusion tensor imaging and 3D T1-weighted imaging. Graph theory network analysis was used to evaluate the brain network at local and global connectivity. In BMS brain, a significant difference of local brain connectivity was recognized at the bilateral rostral anterior cingulate cortex, right medial orbitofrontal cortex, and left pars orbitalis which belong to the medial pain system; however, no significant difference was recognized at the lateral system including the somatic sensory cortex. A strengthened connection of the anterior cingulate cortex and medial prefrontal cortex with the basal ganglia, thalamus, and brain stem was revealed. Structural brain network analysis revealed the alteration of the medial system of the pain-related brain network in chronic pain syndrome.

  2. Introducing Alternative-Based Thresholding for Defining Functional Regions of Interest in fMRI

    Directory of Open Access Journals (Sweden)

    Jasper Degryse

    2017-04-01

    Full Text Available In fMRI research, one often aims to examine activation in specific functional regions of interest (fROIs. Current statistical methods tend to localize fROIs inconsistently, focusing on avoiding detection of false activation. Not missing true activation is however equally important in this context. In this study, we explored the potential of an alternative-based thresholding (ABT procedure, where evidence against the null hypothesis of no effect and evidence against a prespecified alternative hypothesis is measured to control both false positives and false negatives directly. The procedure was validated in the context of localizer tasks on simulated brain images and using a real data set of 100 runs per subject. Voxels categorized as active with ABT can be confidently included in the definition of the fROI, while inactive voxels can be confidently excluded. Additionally, the ABT method complements classic null hypothesis significance testing with valuable information by making a distinction between voxels that show evidence against both the null and alternative and voxels for which the alternative hypothesis cannot be rejected despite lack of evidence against the null.

  3. Presentation of regional cerebral blood flow in amphetamine abusers by 99Tcm-HMPAO brain SPECT

    International Nuclear Information System (INIS)

    Kao, C.H.; Wang, S.J.; Yeh, S.H.

    1994-01-01

    The aim of this study was to describe the effectiveness of 99 Tc m -hexamethylpropyleneamine oxime ( 99 Tc m -HMPAO) brain single photon emission computed tomography (SPECT) in the assessment of the regional cerebral blood flow (rCBF) in amphetamine abusers. Twenty-one amphetamine abusers were included and 99 Tc m -HMPAO brain SPECT performed to evaluate rCBF. The drug-using periods ranged from 1 month to several years. The demonstrated neuropsychogenic symptoms and signs of the abusers were from normal presentation to various neurologic complications. The brain SPECT scans were interpreted visually as either normal or abnormal. The degree of abnormality was classified into mild or severe. The results revealed that (a) most SPECT studies in abusers show small defects (95%, 20/21 cases); 71% (15/21) of cases revealed multiple defects over both hemispheres (classified as severe); 24% (5/21) of the cases had focal defects (classified as mild); and only one case (5%, 1/21) demonstrated a normal SPECT finding; (b) the degree of abnormality on SPECT scans was not related to the dose and duration of drug use or the severity of the neuropsychiatric symptoms and signs. In conclusion, 99 Tc m -HMPAO brain SPECT is a sensitive but not specific test for neuropsychogenic abnormalities associated with amphetamine abuse. (Author)

  4. Automatic segmentation of meningioma from non-contrasted brain MRI integrating fuzzy clustering and region growing

    Directory of Open Access Journals (Sweden)

    Liao Chun-Chih

    2011-08-01

    Full Text Available Abstract Background In recent years, magnetic resonance imaging (MRI has become important in brain tumor diagnosis. Using this modality, physicians can locate specific pathologies by analyzing differences in tissue character presented in different types of MR images. This paper uses an algorithm integrating fuzzy-c-mean (FCM and region growing techniques for automated tumor image segmentation from patients with menigioma. Only non-contrasted T1 and T2 -weighted MR images are included in the analysis. The study's aims are to correctly locate tumors in the images, and to detect those situated in the midline position of the brain. Methods The study used non-contrasted T1- and T2-weighted MR images from 29 patients with menigioma. After FCM clustering, 32 groups of images from each patient group were put through the region-growing procedure for pixels aggregation. Later, using knowledge-based information, the system selected tumor-containing images from these groups and merged them into one tumor image. An alternative semi-supervised method was added at this stage for comparison with the automatic method. Finally, the tumor image was optimized by a morphology operator. Results from automatic segmentation were compared to the "ground truth" (GT on a pixel level. Overall data were then evaluated using a quantified system. Results The quantified parameters, including the "percent match" (PM and "correlation ratio" (CR, suggested a high match between GT and the present study's system, as well as a fair level of correspondence. The results were compatible with those from other related studies. The system successfully detected all of the tumors situated at the midline of brain. Six cases failed in the automatic group. One also failed in the semi-supervised alternative. The remaining five cases presented noticeable edema inside the brain. In the 23 successful cases, the PM and CR values in the two groups were highly related. Conclusions Results indicated

  5. Meta-connectomics: human brain network and connectivity meta-analyses.

    Science.gov (United States)

    Crossley, N A; Fox, P T; Bullmore, E T

    2016-04-01

    Abnormal brain connectivity or network dysfunction has been suggested as a paradigm to understand several psychiatric disorders. We here review the use of novel meta-analytic approaches in neuroscience that go beyond a summary description of existing results by applying network analysis methods to previously published studies and/or publicly accessible databases. We define this strategy of combining connectivity with other brain characteristics as 'meta-connectomics'. For example, we show how network analysis of task-based neuroimaging studies has been used to infer functional co-activation from primary data on regional activations. This approach has been able to relate cognition to functional network topology, demonstrating that the brain is composed of cognitively specialized functional subnetworks or modules, linked by a rich club of cognitively generalized regions that mediate many inter-modular connections. Another major application of meta-connectomics has been efforts to link meta-analytic maps of disorder-related abnormalities or MRI 'lesions' to the complex topology of the normative connectome. This work has highlighted the general importance of network hubs as hotspots for concentration of cortical grey-matter deficits in schizophrenia, Alzheimer's disease and other disorders. Finally, we show how by incorporating cellular and transcriptional data on individual nodes with network models of the connectome, studies have begun to elucidate the microscopic mechanisms underpinning the macroscopic organization of whole-brain networks. We argue that meta-connectomics is an exciting field, providing robust and integrative insights into brain organization that will likely play an important future role in consolidating network models of psychiatric disorders.

  6. How specialized are writing-specific brain regions? An fMRI study of writing, drawing and oral spelling.

    Science.gov (United States)

    Planton, Samuel; Longcamp, Marieke; Péran, Patrice; Démonet, Jean-François; Jucla, Mélanie

    2017-03-01

    Several brain imaging studies identified brain regions that are consistently involved in writing tasks; the left premotor and superior parietal cortices have been associated with the peripheral components of writing performance as opposed to other regions that support the central, orthographic components. Based on a meta-analysis by Planton, Jucla, Roux, and Demonet (2013), we focused on five such writing areas and questioned the task-specificity and hemispheric lateralization profile of the brain response in an functional magnetic resonance imaging (fMRI) experiment where 16 right-handed participants wrote down, spelled out orally object names, and drew shapes from object pictures. All writing-related areas were activated by drawing, and some of them by oral spelling, thus questioning their specialization for written production. The graphemic/motor frontal area (GMFA), a subpart of the superior premotor cortex close to Exner's area (Roux et al., 2009), was the only area with a writing-specific lateralization profile, that is, clear left lateralization during handwriting, and bilateral activity during drawing. Furthermore, the relative lateralization and levels of activation in the superior parietal cortex, ventral premotor cortex, ventral occipitotemporal cortex and right cerebellum across the three tasks brought out new evidence regarding their respective contributions to the writing processes. Copyright © 2016 Elsevier Ltd. All rights reserved.

  7. Regional variation of white matter development in the cat brain revealed by ex vivo diffusion MR tractography.

    Science.gov (United States)

    Dai, Guangping; Das, Avilash; Hayashi, Emiko; Chen, Qin; Takahashi, Emi

    2016-11-01

    Three-dimensional reconstruction of developing fiber pathways is essential to assessing the developmental course of fiber pathways in the whole brain. We applied diffusion spectrum imaging (DSI) tractography to five juvenile ex vivo cat brains at postnatal day (P) 35, when the degree of myelination varies across brain regions. We quantified diffusion properties (fractional anisotropy [FA] and apparent diffusion coefficient [ADC]) and other measurements (number, volume, and voxel count) on reconstructed pathways for projection (cortico-spinal and thalamo-cortical), corpus callosal, limbic (cingulum and fornix), and association (cortico-cortical) pathways, and characterized regional differences in maturation patterns by assessing diffusion properties. FA values were significantly higher in cortico-cortical pathways within the right hemisphere compared to those within the left hemisphere, while the other measurements for the cortico-cortical pathways within the hemisphere did not show asymmetry. ADC values were not asymmetric in both types of pathways. Interestingly, tract count and volume were significantly larger in the left thalamo-cortical pathways compared to the right thalamo-cortical pathways. The bilateral thalamo-cortical pathways showed high FA values compared to the other fiber pathways. On the other hand, ADC values did not show any differences across pathways studied. These results demonstrate that DSI tractography successfully depicted regional variations of white matter tracts during development when myelination is incomplete. Low FA and high ADC values in the cingulum bundle suggest that the cingulum bundle is less mature than the others at this developmental stage. Copyright © 2016 ISDN. Published by Elsevier Ltd. All rights reserved.

  8. Assessment of regional glucose metabolism in aging brain and dementia with positron-emission tomography

    Energy Technology Data Exchange (ETDEWEB)

    Reivich, M.; Alavi, A.; Ferris, S.; Christman, D.; Fowler, J.; MacGregor, R.; Farkas, T.; Greenberg, J.; Dann, R.; Wolf, A.

    1981-01-01

    This paper explores the alterations in regional glucose metabolism that occur in elderly subjects and those with senile dementia compared to normal young volunteers. Results showed a tendency for the frontal regions to have a lower metabolic rate in patients with dementia although this did not reach the level of significance when compared to the elderly control subjects. The changes in glucose metabolism were symmetrical in both the left and right hemispheres. There was a lack of correlation between the mean cortical metabolic rates for glucose and the global mental function in the patients with senile dementia. This is at variance with most of the regional cerebral blood flow data that has been collected. This may be partly related to the use of substrates other than glucose by the brain in elderly and demented subjects. (PSB)

  9. Visual memory and visual mental imagery recruit common control and sensory regions of the brain.

    Science.gov (United States)

    Slotnick, Scott D; Thompson, William L; Kosslyn, Stephen M

    2012-01-01

    Separate lines of research have shown that visual memory and visual mental imagery are mediated by frontal-parietal control regions and can rely on occipital-temporal sensory regions of the brain. We used fMRI to assess the degree to which visual memory and visual mental imagery rely on the same neural substrates. During the familiarization/study phase, participants studied drawings of objects. During the test phase, words corresponding to old and new objects were presented. In the memory test, participants responded "remember," "know," or "new." In the imagery test, participants responded "high vividness," "moderate vividness," or "low vividness." Visual memory (old-remember) and visual imagery (old-high vividness) were commonly associated with activity in frontal-parietal control regions and occipital-temporal sensory regions. In addition, visual memory produced greater activity than visual imagery in parietal and occipital-temporal regions. The present results suggest that visual memory and visual imagery rely on highly similar--but not identical--cognitive processes.

  10. "Facilitated" amino acid transport is upregulated in brain tumors.

    Science.gov (United States)

    Miyagawa, T; Oku, T; Uehara, H; Desai, R; Beattie, B; Tjuvajev, J; Blasberg, R

    1998-05-01

    The goal of this study was to determine the magnitude of "facilitated" amino acid transport across tumor and brain capillaries and to evaluate whether amino acid transporter expression is "upregulated" in tumor vessels compared to capillaries in contralateral brain tissue. Aminocyclopentane carboxylic acid (ACPC), a non-metabolized [14C]-labeled amino acid, and a reference molecule for passive vascular permeability, [67Ga]-gallium-diethylenetriaminepentaacetic acid (Ga-DTPA), were used in these studies. Two experimental rat gliomas were studied (C6 and RG2). Brain tissue was rapidly processed for double label quantitative autoradiography 10 minutes after intravenous injection of ACPC and Ga-DTPA. Parametric images of blood-to-brain transport (K1ACPC and K1Ga-DTPA, microL/min/g) produced from the autoradiograms and the histology were obtained from the same tissue section. These three images were registered in an image array processor; regions of interest in tumor and contralateral brain were defined on morphologic criteria (histology) and were transferred to the autoradiographic images to obtain mean values. The facilitated component of ACPC transport (deltaK1ACPC) was calculated from the K1ACPC and K1Ga-DTPA data, and paired comparisons between tumor and contralateral brain were performed. ACPC flux, K1ACPC, across normal brain capillaries (22.6 +/- 8.1 microL/g/min) was >200-fold greater than that of Ga-DTPA (0.09 +/- 0.04 microL/g/min), and this difference was largely (approximately 90%) due to facilitated ACPC transport. Substantially higher K1ACPC values compared to corresponding K1DTPA values were also measured in C6 and RG2 gliomas. The deltaK1ACPC values for C6 glioma were more than twice that of contralateral brain cortex. K1ACPC and deltaK1ACPC values for RG2 gliomas was not significantly higher than that of contralateral cortex, although a approximately 2-fold difference in facilitated transport is obtained after normalization for differences in capillary

  11. Disruption of functional networks in dyslexia: A whole-brain, data-driven analysis of connectivity

    Science.gov (United States)

    Finn, Emily S.; Shen, Xilin; Holahan, John M.; Scheinost, Dustin; Lacadie, Cheryl; Papademetris, Xenophon; Shaywitz, Sally E.; Shaywitz, Bennett A.; Constable, R. Todd

    2013-01-01

    Background Functional connectivity analyses of fMRI data are a powerful tool for characterizing brain networks and how they are disrupted in neural disorders. However, many such analyses examine only one or a small number of a priori seed regions. Studies that consider the whole brain frequently rely on anatomic atlases to define network nodes, which may result in mixing distinct activation timecourses within a single node. Here, we improve upon previous methods by using a data-driven brain parcellation to compare connectivity profiles of dyslexic (DYS) versus non-impaired (NI) readers in the first whole-brain functional connectivity analysis of dyslexia. Methods Whole-brain connectivity was assessed in children (n = 75; 43 NI, 32 DYS) and adult (n = 104; 64 NI, 40 DYS) readers. Results Compared to NI readers, DYS readers showed divergent connectivity within the visual pathway and between visual association areas and prefrontal attention areas; increased right-hemisphere connectivity; reduced connectivity in the visual word-form area (part of the left fusiform gyrus specialized for printed words); and persistent connectivity to anterior language regions around the inferior frontal gyrus. Conclusions Together, findings suggest that NI readers are better able to integrate visual information and modulate their attention to visual stimuli, allowing them to recognize words based on their visual properties, while DYS readers recruit altered reading circuits and rely on laborious phonology-based “sounding out” strategies into adulthood. These results deepen our understanding of the neural basis of dyslexia and highlight the importance of synchrony between diverse brain regions for successful reading. PMID:24124929

  12. Brain volume measurement using three-dimensional magnetic resonance images

    International Nuclear Information System (INIS)

    Ishimaru, Yoshihiro

    1996-01-01

    This study was designed to validate accurate measurement method of human brain volume using three dimensional (3D) MRI data on a workstation, and to establish optimal correcting method of human brain volume on diagnosis of brain atrophy. 3D MRI data were acquired by fast SPGR sequence using 1.5 T MR imager. 3D MRI data were segmented by region growing method and 3D image was displayed by surface rendering method on the workstation. Brain volume was measured by the volume measurement function of the workstation. In order to validate the accurate measurement method, phantoms and a specimen of human brain were examined. Phantom volume was measured by changing the lower level of threshold value. At the appropriate threshold value, percentage of error of phantoms and the specimen were within 0.6% and 0.08%, respectively. To establish the optimal correcting method, 130 normal volunteers were examined. Brain volumes corrected with height weight, body surface area, and alternative skull volume were evaluated. Brain volume index, which is defined as dividing brain volume by alternative skull volume, had the best correlation with age (r=0.624, p<0.05). No gender differences was observed in brain volume index in contrast to in brain volume. The clinical usefulness of this correcting method for brain atrophy diagnosis was evaluated in 85 patients. Diagnosis by 2D spin echo MR images was compared with brain volume index. Diagnosis of brain atrophy by 2D MR image was concordant with the evaluation by brain volume index. These results indicated that this measurement method had high accuracy, and it was important to set the appropriate threshold value. Brain volume index was the appropriate indication for evaluation of human brain volume, and was considered to be useful for the diagnosis of brain atrophy. (author)

  13. Region-selective effects of long-term lithium and carbamazepine administration on cyclic AMP levels in rat brain

    International Nuclear Information System (INIS)

    Wiborg, Ove; Krueger, Tanja; Jakosen, Soeren N.

    1999-01-01

    The effect of lithium and carbamazepine in the treatment of bipolar affective disorder is well established. Althougt a number of biochemical effects have been found, the exact molecular mechanisms underlying their therapeutic actions have not been elucidated nor are the target regions in the brain identified. Taken into account the important role of the cyclic AMP second messenger system in the regulation of neuronal exitability and the indications of its involvement in the pathophysiology of bipolar affective disorder, we have focused on the drug effects on cyclic AMP levels. The objectives of this investigation were to measure the effects on basal cyclic AMP levels, and to locate target regions within the rat brain after long-term administration of lithium and carbamazepine. Drug treatments were carried out for a period of 28 days. After either drug treatment the cyclic AMP level was increased 3-4 times in frontal cortex but unchanged in hippocampus, hypothalamus, thalamus, amygdala and in cerebellum. In neostratum the cyclic AMP level was decreased to about 30% after treatment with lithium. We suggest the common region-selective effect, observed for both drugs in frontal cortex, to be essential for the therapeutic actions of lithium and carbamazepine. (au)

  14. Integration of temporal and spatial properties of dynamic connectivity networks for automatic diagnosis of brain disease.

    Science.gov (United States)

    Jie, Biao; Liu, Mingxia; Shen, Dinggang

    2018-07-01

    Functional connectivity networks (FCNs) using resting-state functional magnetic resonance imaging (rs-fMRI) have been applied to the analysis and diagnosis of brain disease, such as Alzheimer's disease (AD) and its prodrome, i.e., mild cognitive impairment (MCI). Different from conventional studies focusing on static descriptions on functional connectivity (FC) between brain regions in rs-fMRI, recent studies have resorted to dynamic connectivity networks (DCNs) to characterize the dynamic changes of FC, since dynamic changes of FC may indicate changes in macroscopic neural activity patterns in cognitive and behavioral aspects. However, most of the existing studies only investigate the temporal properties of DCNs (e.g., temporal variability of FC between specific brain regions), ignoring the important spatial properties of the network (e.g., spatial variability of FC associated with a specific brain region). Also, emerging evidence on FCNs has suggested that, besides temporal variability, there is significant spatial variability of activity foci over time. Hence, integrating both temporal and spatial properties of DCNs can intuitively promote the performance of connectivity-network-based learning methods. In this paper, we first define a new measure to characterize the spatial variability of DCNs, and then propose a novel learning framework to integrate both temporal and spatial variabilities of DCNs for automatic brain disease diagnosis. Specifically, we first construct DCNs from the rs-fMRI time series at successive non-overlapping time windows. Then, we characterize the spatial variability of a specific brain region by computing the correlation of functional sequences (i.e., the changing profile of FC between a pair of brain regions within all time windows) associated with this region. Furthermore, we extract both temporal variabilities and spatial variabilities from DCNs as features, and integrate them for classification by using manifold regularized multi

  15. Arteriolosclerosis that affects multiple brain regions is linked to hippocampal sclerosis of ageing.

    Science.gov (United States)

    Neltner, Janna H; Abner, Erin L; Baker, Steven; Schmitt, Frederick A; Kryscio, Richard J; Jicha, Gregory A; Smith, Charles D; Hammack, Eleanor; Kukull, Walter A; Brenowitz, Willa D; Van Eldik, Linda J; Nelson, Peter T

    2014-01-01

    Hippocampal sclerosis of ageing is a prevalent brain disease that afflicts older persons and has been linked with cerebrovascular pathology. Arteriolosclerosis is a subtype of cerebrovascular pathology characterized by concentrically thickened arterioles. Here we report data from multiple large autopsy series (University of Kentucky Alzheimer's Disease Centre, Nun Study, and National Alzheimer's Coordinating Centre) showing a specific association between hippocampal sclerosis of ageing pathology and arteriolosclerosis. The present analyses incorporate 226 cases of autopsy-proven hippocampal sclerosis of ageing and 1792 controls. Case-control comparisons were performed including digital pathological assessments for detailed analyses of blood vessel morphology. We found no evidence of associations between hippocampal sclerosis of ageing pathology and lacunar infarcts, large infarcts, Circle of Willis atherosclerosis, or cerebral amyloid angiopathy. Individuals with hippocampal sclerosis of ageing pathology did not show increased rates of clinically documented hypertension, diabetes, or other cardiac risk factors. The correlation between arteriolosclerosis and hippocampal sclerosis of ageing pathology was strong in multiple brain regions outside of the hippocampus. For example, the presence of arteriolosclerosis in the frontal cortex (Brodmann area 9) was strongly associated with hippocampal sclerosis of ageing pathology (P studies to optimize immunostaining methods for small blood vessel visualization, our analyses focused on sections immunostained for smooth muscle actin (a marker of arterioles) and CD34 (an endothelial marker), with separate analyses on grey and white matter. A total of 43 834 smooth muscle actin-positive vascular profiles and 603 798 CD34-positive vascular profiles were evaluated. In frontal cortex of cases with hippocampal sclerosis of ageing, smooth muscle actin-immunoreactive arterioles had thicker walls (P < 0.05), larger perimeters (P < 0

  16. Region-selective effects of neuroinflammation and antioxidant treatment on peripheral benzodiazepine receptors and NMDA receptors in the rat brain

    Energy Technology Data Exchange (ETDEWEB)

    Biegon, A.; Alvarado, M.; Budinger, T.F.; Grossman, R.; Hensley, K.; West, M.S.; Kotake, Y.; Ono, M.; Floyd, R.A.

    2001-12-10

    Following induction of acute neuroinflammation by intracisternal injection of endotoxin (lipopolysaccharide) in rats, quantitative autoradiography was used to assess the regional level of microglial activation and glutamate (NMDA) receptor binding. The possible protective action of the antioxidant phenyl-tert-butyl nitrone in this model was tested by administering the drug in the drinking water for 6 days starting 24 hours after endotoxin injection. Animals were killed 7 days post-injection and consecutive cryostat brain sections labeled with [3H]PK11195 as a marker of activated microglia and [125I]iodoMK801 as a marker of the open-channel, activated state of NMDA receptors. Lipopolysaccharide increased [3H]PK11195 binding in the brain, with the largest increases (2-3 fold) in temporal and entorhinal cortex, hippocampus, and substantia innominata. A significant (>50 percent) decrease in [125I]iodoMK801 binding was found in the same brain regions. Phenyl-tert-butyl nitrone treatment resulted in a partial inhibition ({approx}25 percent decrease) of the lipopolysaccharide-induced increase in [3H]PK11195 binding but completely reversed the lipopolysaccharide-induced decrease in [125I]iodoMK80 binding in the entorhinal cortex, hippocampus, and substantia innominata. Loss of NMDA receptor function in cortical and hippocampal regions may contribute to the cognitive deficits observed in diseases with a neuroinflammatory component, such as meningitis or Alzheimer's disease.

  17. Optogenetic fMRI and electrophysiological identification of region-specific connectivity between the cerebellar cortex and forebrain.

    Science.gov (United States)

    Choe, Katrina Y; Sanchez, Carlos F; Harris, Neil G; Otis, Thomas S; Mathews, Paul J

    2018-06-01

    Complex animal behavior is produced by dynamic interactions between discrete regions of the brain. As such, defining functional connections between brain regions is critical in gaining a full understanding of how the brain generates behavior. Evidence suggests that discrete regions of the cerebellar cortex functionally project to the forebrain, mediating long-range communication potentially important in motor and non-motor behaviors. However, the connectivity map remains largely incomplete owing to the challenge of driving both reliable and selective output from the cerebellar cortex, as well as the need for methods to detect region specific activation across the entire forebrain. Here we utilize a paired optogenetic and fMRI (ofMRI) approach to elucidate the downstream forebrain regions modulated by activating a region of the cerebellum that induces stereotypical, ipsilateral forelimb movements. We demonstrate with ofMRI, that activating this forelimb motor region of the cerebellar cortex results in functional activation of a variety of forebrain and midbrain areas of the brain, including the hippocampus and primary motor, retrosplenial and anterior cingulate cortices. We further validate these findings using optogenetic stimulation paired with multi-electrode array recordings and post-hoc staining for molecular markers of activated neurons (i.e. c-Fos). Together, these findings demonstrate that a single discrete region of the cerebellar cortex is capable of influencing motor output and the activity of a number of downstream forebrain as well as midbrain regions thought to be involved in different aspects of behavior. Copyright © 2018 Elsevier Inc. All rights reserved.

  18. Regional alterations of brain biogenic amines and GABA/glutamate levels in rats following chronic lead exposure during neonatal development

    Energy Technology Data Exchange (ETDEWEB)

    Shailesh Kumar, M V; Desiraju, T [National Inst. of Mental Health and Neuro Sciences, Bangalore (India). Dept. of Neurophysiology

    1990-06-01

    Wistar rat pups were administered either a high dose of lead acetate (400 {mu}g lead-g body weight/day) or a low dose (100 {mu}g lead/g body weight/day) by gastric intubation, from 2 days through 60 days of age. The rats on both these doses exhibited statistically significant decreases in body and brain weights throughout the lead treatment period. A group of rats on high dose was also rehabilitated by discontinuing the lead from 60 days of age. In these rats, at 160 days of age, the body weight but not the brain weight recovered to normal levels. During the lead intake, the rats on high dose revealed significant elevations in the levels of noradrenaline (NA) in the hippocampus (HI), cerebellum (CE), hypothalamus (HY), brainstem (BS), and accumbens-striatum (SA). The elevated levels in all the above regions except in the HY persisted even after rehabilitation. The dopamine (DA) levels changed significantly in opposite directions in HY (elevation) and BS (reduction) during the lead treatment, and the HY recovered after rehabilitation. Under lead, the serotonin (5HT) levels were elevated significantly in the HI, BS and MC (motor cortex), while after rehabilitation the abnormality persisted only in the MC. Low dose lead treatment was also effective on the same areas of brain. In the low dose group, estimation of the levels of GABA and glutamate were also done, and a significant decrease of GABA in CE and glutamate in MC was observed. The differences observed in the neurotoxic effects (none or significant) of lead in the different regions for each of the transmitters (NA, DA, 5HT) supports the interesting conclusion that the vulnerability of the axon terminals of any given type is dependent on some regional factors, although the projections of the different regions originate from an apparently similar category of neurons in the brain stem. (orig.).

  19. A SPECT study of language and brain reorganization three years after pediatric brain injury.

    Science.gov (United States)

    Chiu Wong, Stephanie B; Chapman, Sandra B; Cook, Lois G; Anand, Raksha; Gamino, Jacquelyn F; Devous, Michael D

    2006-01-01

    Using single photon emission computed tomography (SPECT), we investigated brain plasticity in children 3 years after sustaining a severe traumatic brain injury (TBI). First, we assessed brain perfusion patterns (i.e., the extent of brain blood flow to regions of the brain) at rest in eight children who suffered severe TBI as compared to perfusion patterns in eight normally developing children. Second, we examined differences in perfusion between children with severe TBI who showed good versus poor recovery in complex discourse skills. Specifically, the children were asked to produce and abstract core meaning for two stories in the form of a lesson. Inconsistent with our predictions, children with severe TBI showed areas of increased perfusion as compared to normally developing controls. Adult studies have shown the reverse pattern with TBI associated with reduced perfusion. With regard to the second aim and consistent with previously identified brain-discourse relations, we found a strong positive association between perfusion in right frontal regions and discourse abstraction abilities, with higher perfusion linked to better discourse outcomes and lower perfusion linked to poorer discourse outcomes. Furthermore, brain-discourse patterns of increased perfusion in left frontal regions were associated with lower discourse abstraction ability. The results are discussed in terms of how brain changes may represent adaptive and maladaptive plasticity. The findings offer direction for future studies of brain plasticity in response to neurocognitive treatments.

  20. STATISTICAL GROWTH MODELING OF LONGITUDINAL DT-MRI FOR REGIONAL CHARACTERIZATION OF EARLY BRAIN DEVELOPMENT.

    Science.gov (United States)

    Sadeghi, Neda; Prastawa, Marcel; Fletcher, P Thomas; Gilmore, John H; Lin, Weili; Gerig, Guido

    2012-01-01

    A population growth model that represents the growth trajectories of individual subjects is critical to study and understand neurodevelopment. This paper presents a framework for jointly estimating and modeling individual and population growth trajectories, and determining significant regional differences in growth pattern characteristics applied to longitudinal neuroimaging data. We use non-linear mixed effect modeling where temporal change is modeled by the Gompertz function. The Gompertz function uses intuitive parameters related to delay, rate of change, and expected asymptotic value; all descriptive measures which can answer clinical questions related to growth. Our proposed framework combines nonlinear modeling of individual trajectories, population analysis, and testing for regional differences. We apply this framework to the study of early maturation in white matter regions as measured with diffusion tensor imaging (DTI). Regional differences between anatomical regions of interest that are known to mature differently are analyzed and quantified. Experiments with image data from a large ongoing clinical study show that our framework provides descriptive, quantitative information on growth trajectories that can be directly interpreted by clinicians. To our knowledge, this is the first longitudinal analysis of growth functions to explain the trajectory of early brain maturation as it is represented in DTI.

  1. Structural connectivity asymmetry in the neonatal brain.

    Science.gov (United States)

    Ratnarajah, Nagulan; Rifkin-Graboi, Anne; Fortier, Marielle V; Chong, Yap Seng; Kwek, Kenneth; Saw, Seang-Mei; Godfrey, Keith M; Gluckman, Peter D; Meaney, Michael J; Qiu, Anqi

    2013-07-15

    Asymmetry of the neonatal brain is not yet understood at the level of structural connectivity. We utilized DTI deterministic tractography and structural network analysis based on graph theory to determine the pattern of structural connectivity asymmetry in 124 normal neonates. We tracted white matter axonal pathways characterizing interregional connections among brain regions and inferred asymmetry in left and right anatomical network properties. Our findings revealed that in neonates, small-world characteristics were exhibited, but did not differ between the two hemispheres, suggesting that neighboring brain regions connect tightly with each other, and that one region is only a few paths away from any other region within each hemisphere. Moreover, the neonatal brain showed greater structural efficiency in the left hemisphere than that in the right. In neonates, brain regions involved in motor, language, and memory functions play crucial roles in efficient communication in the left hemisphere, while brain regions involved in emotional processes play crucial roles in efficient communication in the right hemisphere. These findings suggest that even at birth, the topology of each cerebral hemisphere is organized in an efficient and compact manner that maps onto asymmetric functional specializations seen in adults, implying lateralized brain functions in infancy. Copyright © 2013 Elsevier Inc. All rights reserved.

  2. Analysis of a human brain transcriptome map

    Directory of Open Access Journals (Sweden)

    Greene Jonathan R

    2002-04-01

    Full Text Available Abstract Background Genome wide transcriptome maps can provide tools to identify candidate genes that are over-expressed or silenced in certain disease tissue and increase our understanding of the structure and organization of the genome. Expressed Sequence Tags (ESTs from the public dbEST and proprietary Incyte LifeSeq databases were used to derive a transcript map in conjunction with the working draft assembly of the human genome sequence. Results Examination of ESTs derived from brain tissues (excluding brain tumor tissues suggests that these genes are distributed on chromosomes in a non-random fashion. Some regions on the genome are dense with brain-enriched genes while some regions lack brain-enriched genes, suggesting a significant correlation between distribution of genes along the chromosome and tissue type. ESTs from brain tumor tissues have also been mapped to the human genome working draft. We reveal that some regions enriched in brain genes show a significant decrease in gene expression in brain tumors, and, conversely that some regions lacking in brain genes show an increased level of gene expression in brain tumors. Conclusions This report demonstrates a novel approach for tissue specific transcriptome mapping using EST-based quantitative assessment.

  3. Congenital olfactory impairment is linked to cortical changes in prefrontal and limbic brain regions

    DEFF Research Database (Denmark)

    Karstensen, Helena Gásdal; Vestergaard, Martin; Baaré, William F C

    2018-01-01

    differently in individuals who suffer from lifelong olfactory deprivation relative to healthy normosmic individuals. To address this question, we examined if regional variations in gray matter volume were associated with smell ability in seventeen individuals with isolated congenital olfactory impairment (COI...... in left middle frontal gyrus and right superior frontal sulcus (SFS). COI subjects with severe olfactory impairment (anosmia) had reduced grey matter volume in the left mOFC and increased volume in right piriform cortex and SFS. Within the COI group olfactory ability, measured with the "Sniffin' Sticks...... piriform cortex, while olfactory identification was negatively associated with right SFS volume. Our findings suggest that lifelong olfactory deprivation trigger changes in the cortical volume of prefrontal and limbic brain regions previously linked to olfactory memory....

  4. A three-plane architectonic atlas of the rat hippocampal region.

    Science.gov (United States)

    Boccara, Charlotte N; Kjonigsen, Lisa J; Hammer, Ingvild M; Bjaalie, Jan G; Leergaard, Trygve B; Witter, Menno P

    2015-07-01

    The hippocampal region, comprising the hippocampal formation and the parahippocampal region, has been one of the most intensively studied parts of the brain for decades. Better understanding of its functional diversity and complexity has led to an increased demand for specificity in experimental procedures and manipulations. In view of the complex 3D structure of the hippocampal region, precisely positioned experimental approaches require a fine-grained architectural description that is available and readable to experimentalists lacking detailed anatomical experience. In this paper, we provide the first cyto- and chemoarchitectural description of the hippocampal formation and parahippocampal region in the rat at high resolution and in the three standard sectional planes: coronal, horizontal and sagittal. The atlas uses a series of adjacent sections stained for neurons and for a number of chemical marker substances, particularly parvalbumin and calbindin. All the borders defined in one plane have been cross-checked against their counterparts in the other two planes. The entire dataset will be made available as a web-based interactive application through the Rodent Brain WorkBench (http://www.rbwb.org) which, together with this paper, provides a unique atlas resource. © 2014 Wiley Periodicals, Inc.

  5. Regional difference of radiosensitivity of neural cells in the fetal brain of mice on day 13 of gestation

    International Nuclear Information System (INIS)

    Hoshino, Kiyoshi; Kameyama, Yoshiro

    1986-01-01

    Pregnant Slc: ICR mice were exposed to a single whole-body X-irradiation at a dose of 12.5 R or 25 R on day 13 of gestation. After irradiation, fetuses were obtained from mothers at 1- or 3-hour intervals and coronal histological sections were made. Pyknotic cells were counted in the ventricular zone of brain mantle, hippocampal anlage and olfactory bulb. In the 25 R group, peak incidences of pyknotic cells in brain mantle, hippocampal anlage and olfactory bulb were 13.2 %, 6.9 % and 2.2 %, respectively. In the 12.5 R group, these were 6.0 %, 3.2 % and 1.7 %, respectively. This result indicates that neural cells in the ventricular zone of brain mantle are the most radiosensitive among the cerebral regions examined in day-13 mouse fetuses. (author)

  6. Over-all accuracy of sup(99m)Tc-pertechnetate brain scanning for brain tumours

    International Nuclear Information System (INIS)

    Bjoernsson, O.G.; Petursson, E.; Sigurbjoernsson, B.; Davidsson, D.

    1978-01-01

    A 3-year follow-up and re-evaluation of all scans on all patients referred for brain scanning in Iceland during 1 year was performed in order to assess the diagnostic reliability of radioisotope scanning for brain tumours. The study included 471 patients. Of these 25 had primary brain tumours and 7 brain metastases. Scans were positive and correctly interpreted in 68% of the patients with primary brain tumours and in 3 of the 7 patients with metastases. The over-all accuracy of brain scanning for brain tumours defined as the total number of correct positive scans and correct negative scans versus total number of scans examined was 96%, this figure being mainly influenced by the high number of true negative scans. (orig.) [de

  7. Region-specific differences in bioenergetic proteins and protein response to acute high fat diet in brains of low and high capacity runner rats.

    Science.gov (United States)

    Gan, Li; Ma, Delin; Li, Min; Yang, Fu-Chen; Rogers, Robert S; Wheatley, Joshua L; Koch, Lauren G; Britton, Steven L; Thyfault, John P; Geiger, Paige C; Stanford, John A

    2018-05-01

    Aerobic capacity is a strong predictor of mortality. Low capacity runner (LCR) rats exhibit reduced mitochondrial function in peripheral organs. A high fat diet (HFD) can worsen metabolic phenotype in LCR rats. Little is known about metabolic changes in the brains of these rats, however. This study examined protein markers of mitochondrial function and metabolism as a function of aerobic running capacity and an acute HFD in four brain regions: the striatum, hippocampus, hypothalamus, and substantia nigra. After 3 days HFD or chow diets, we measured peroxisome proliferator-activated receptor-γ coactivator 1α (PGC1-α), nuclear respiratory factors 1 (Nrf-1), mitochondrial transcription factor A (TFAM), and phosphorylated (activated) AMP-activated protein kinase (p-AMPK) protein levels in the four brain regions. LCR rats exhibited lower levels of mitochondrial proteins (PGC1-α, Nrf-1, TFAM), and greater p-AMPK, in striatum, but not in the other brain regions. Mitochondrial protein levels were greater in HFD LCR striatum, while p-AMPK was lower in this group. Markers of lower mitochondrial biogenesis and increased metabolic demand were limited to the LCR striatum, which nevertheless maintained the capacity to respond to an acute HFD challenge. Copyright © 2018 Elsevier B.V. All rights reserved.

  8. Unveiling the neurotoxicity of methylmercury in fish (Diplodus sargus) through a regional morphometric analysis of brain and swimming behavior assessment.

    Science.gov (United States)

    Puga, Sónia; Pereira, Patrícia; Pinto-Ribeiro, Filipa; O'Driscoll, Nelson J; Mann, Erin; Barata, Marisa; Pousão-Ferreira, Pedro; Canário, João; Almeida, Armando; Pacheco, Mário

    2016-11-01

    The current study aims to shed light on the neurotoxicity of MeHg in fish (white seabream - Diplodus sargus) by the combined assessment of: (i) MeHg toxicokinetics in the brain, (ii) brain morphometry (volume and number of neurons plus glial cells in specific brain regions) and (iii) fish swimming behavior (endpoints associated with the motor performance and the fear/anxiety-like status). Fish were surveyed for all the components after 7 (E7) and 14 (E14) days of dietary exposure to MeHg (8.7μgg -1 ), as well as after a post-exposure period of 28days (PE28). MeHg was accumulated in the brain of D. sargus after a short time (E7) and reached a maximum at the end of the exposure period (E14), suggesting an efficient transport of this toxicant into fish brain. Divalent inorganic Hg was also detected in fish brain along the experiment (indicating demethylation reactions), although levels were 100-200 times lower than MeHg, which pinpoints the organic counterpart as the great liable for the recorded effects. In this regard, a decreased number of cells in medial pallium and optic tectum, as well as an increased hypothalamic volume, occurred at E7. Such morphometric alterations were followed by an impairment of fish motor condition as evidenced by a decrease in the total swimming time, while the fear/anxiety-like status was not altered. Moreover, at E14 fish swam a greater distance, although no morphometric alterations were found in any of the brain areas, probably due to compensatory mechanisms. Additionally, although MeHg decreased almost two-fold in the brain during post-exposure, the levels were still high and led to a loss of cells in the optic tectum at PE28. This is an interesting result that highlights the optic tectum as particularly vulnerable to MeHg exposure in fish. Despite the morphometric alterations reported in the optic tectum at PE28, no significant changes were found in fish behavior. Globally, the effects of MeHg followed a multiphasic profile, where

  9. Effects of tetrahydrocannabinol on glucose uptake in the rat brain.

    Science.gov (United States)

    Miederer, I; Uebbing, K; Röhrich, J; Maus, S; Bausbacher, N; Krauter, K; Weyer-Elberich, V; Lutz, B; Schreckenberger, M; Urban, R

    2017-05-01

    Δ 9 -Tetrahydrocannabinol (THC) is the psychoactive component of the plant Cannabis sativa and acts as a partial agonist at cannabinoid type 1 and type 2 receptors in the brain. The goal of this study was to assess the effect of THC on the cerebral glucose uptake in the rat brain. 21 male Sprague Dawley rats (12-13 w) were examined and received five different doses of THC ranging from 0.01 to 1 mg/kg. For data acquisition a Focus 120 small animal PET scanner was used and 24.1-28.0 MBq of [ 18 F]-fluoro-2-deoxy-d-glucose were injected. The data were acquired for 70 min and arterial blood samples were collected throughout the scan. THC, THC-OH and THC-COOH were determined at 55 min p.i. Nine volumes of interest were defined, and the cerebral glucose uptake was calculated for each brain region. Low blood THC levels of glucose uptake (6-30 %), particularly in the hypothalamus (p = 0.007), while blood THC levels > 10 ng/ml (injected dose: ≥ 0.05 mg/kg) coincided with a decreased glucose uptake (-2 to -22 %), especially in the cerebellar cortex (p = 0.008). The effective concentration in this region was estimated 2.4 ng/ml. This glucose PET study showed that stimulation of CB1 receptors by THC affects the glucose uptake in the rat brain, whereby the effect of THC is regionally different and dependent on dose - an effect that may be of relevance in behavioural studies. Copyright © 2017 Elsevier Ltd. All rights reserved.

  10. Region-selective effects of long-term lithium and carbamazepine administration on cyclic AMP levels in rat brain

    Energy Technology Data Exchange (ETDEWEB)

    Wiborg, Ove; Krueger, Tanja; Jakosen, Soeren N. [Psychiatric Hospital, Dept. of Biological Psychiatry, Risskov (Denmark)

    1999-02-01

    The effect of lithium and carbamazepine in the treatment of bipolar affective disorder is well established. Althougt a number of biochemical effects have been found, the exact molecular mechanisms underlying their therapeutic actions have not been elucidated nor are the target regions in the brain identified. Taken into account the important role of the cyclic AMP second messenger system in the regulation of neuronal exitability and the indications of its involvement in the pathophysiology of bipolar affective disorder, we have focused on the drug effects on cyclic AMP levels. The objectives of this investigation were to measure the effects on basal cyclic AMP levels, and to locate target regions within the rat brain after long-term administration of lithium and carbamazepine. Drug treatments were carried out for a period of 28 days. After either drug treatment the cyclic AMP level was increased 3-4 times in frontal cortex but unchanged in hippocampus, hypothalamus, thalamus, amygdala and in cerebellum. In neostratum the cyclic AMP level was decreased to about 30% after treatment with lithium. We suggest the common region-selective effect, observed for both drugs in frontal cortex, to be essential for the therapeutic actions of lithium and carbamazepine. (au) 46 refs.

  11. On brain activity mapping: insights and lessons from Brain Decoding Project to map memory patterns in the hippocampus.

    Science.gov (United States)

    Tsien, Joe Z; Li, Meng; Osan, Remus; Chen, Guifen; Lin, Longnian; Wang, Phillip Lei; Frey, Sabine; Frey, Julietta; Zhu, Dajiang; Liu, Tianming; Zhao, Fang; Kuang, Hui

    2013-09-01

    The BRAIN project recently announced by the president Obama is the reflection of unrelenting human quest for cracking the brain code, the patterns of neuronal activity that define who we are and what we are. While the Brain Activity Mapping proposal has rightly emphasized on the need to develop new technologies for measuring every spike from every neuron, it might be helpful to consider both the theoretical and experimental aspects that would accelerate our search for the organizing principles of the brain code. Here we share several insights and lessons from the similar proposal, namely, Brain Decoding Project that we initiated since 2007. We provide a specific example in our initial mapping of real-time memory traces from one part of the memory circuit, namely, the CA1 region of the mouse hippocampus. We show how innovative behavioral tasks and appropriate mathematical analyses of large datasets can play equally, if not more, important roles in uncovering the specific-to-general feature-coding cell assembly mechanism by which episodic memory, semantic knowledge, and imagination are generated and organized. Our own experiences suggest that the bottleneck of the Brain Project is not only at merely developing additional new technologies, but also the lack of efficient avenues to disseminate cutting edge platforms and decoding expertise to neuroscience community. Therefore, we propose that in order to harness unique insights and extensive knowledge from various investigators working in diverse neuroscience subfields, ranging from perception and emotion to memory and social behaviors, the BRAIN project should create a set of International and National Brain Decoding Centers at which cutting-edge recording technologies and expertise on analyzing large datasets analyses can be made readily available to the entire community of neuroscientists who can apply and schedule to perform cutting-edge research.

  12. Ontogenetic Shape Change in the Chicken Brain: Implications for Paleontology.

    Science.gov (United States)

    Kawabe, Soichiro; Matsuda, Seiji; Tsunekawa, Naoki; Endo, Hideki

    2015-01-01

    Paleontologists have investigated brain morphology of extinct birds with little information on post-hatching changes in avian brain morphology. Without the knowledge of ontogenesis, assessing brain morphology in fossil taxa could lead to misinterpretation of the phylogeny or neurosensory development of extinct species. Hence, it is imperative to determine how avian brain morphology changes during post-hatching growth. In this study, chicken brain shape was compared at various developmental stages using three-dimensional (3D) geometric morphometric analysis and the growth rate of brain regions was evaluated to explore post-hatching morphological changes. Microscopic MRI (μMRI) was used to acquire in vivo data from living and post-mortem chicken brains. The telencephalon rotates caudoventrally during growth. This change in shape leads to a relative caudodorsal rotation of the cerebellum and myelencephalon. In addition, all brain regions elongate rostrocaudally and this leads to a more slender brain shape. The growth rates of each brain region were constant and the slopes from the growth formula were parallel. The dominant pattern of ontogenetic shape change corresponded with interspecific shape changes due to increasing brain size. That is, the interspecific and ontogenetic changes in brain shape due to increased size have similar patterns. Although the shape of the brain and each brain region changed considerably, the volume ratio of each brain region did not change. This suggests that the brain can change its shape after completing functional differentiation of the brain regions. Moreover, these results show that consideration of ontogenetic changes in brain shape is necessary for an accurate assessment of brain morphology in paleontological studies.

  13. Region-specific changes in brain diffusivity in fetal isolated mild ventriculomegaly

    Energy Technology Data Exchange (ETDEWEB)

    Yaniv, Gal [Sheba Medical Center, Department of Diagnostic Imaging, Tel Aviv (Israel); The Hebrew University of Jerusalem, The Institute for Research in Military Medicine, The Faculty of Medicine, Jerusalem (Israel); Sheba Medical Center, The Dr. Pinchas Bornstein Talpiot Medical Leadership Program, Tel Aviv (Israel); Katorza, Eldad [Sheba Medical Center, Obstetrics and Gynecology Department, Tel Aviv (Israel); Bercovitz, Ronen; Bergman, Dafi; Greenberg, Gahl; Hoffmann, Chen [Sheba Medical Center, Department of Diagnostic Imaging, Tel Aviv (Israel); Biegon, Anat [Stony Brook University School of Medicine, Department of Neurology, Stony Brook, NY (United States)

    2016-03-15

    To evaluate the impact of symmetric and asymmetric isolated mild ventriculomegaly (IMVM, atrial width 10-15 mm) on apparent diffusion coefficient (ADC) values in fetal brain areas. Sixty-seven sequential fetal head magnetic resonance imaging scans (feMRI) of VM cases performed between 2009 and 2014 were compared to 38 normal feMRI scans matched for gestational age (controls). Ultrasound- and MRI-proven IMVM cases were divided into asymmetrical (AVM, ≥2 mm difference in atrial width), symmetrical (SVM, <2 mm difference in atrial width), and asymmetrical IMVM with one normal-sized ventricle (AV1norm). ADC values were significantly elevated in the basal ganglia (BG) of the SVM and AV1norm groups compared to controls (p < 0.004 and p < 0.013, respectively). High diffusivity was constantly detected in the BG ipsilateral to the enlarged atria relative to the normal-sized atria in the AV1norm group (p < 0.03). Frontal lobe ADC values were significantly reduced in the AVM and SVM groups (p < 0.003 and p < 0.003 vs. controls). Temporal lobe ADC values were significantly reduced in the AVM group (p < 0.001 vs. controls). Isolated mild ventriculomegaly is associated with distinct ADC value changes in different brain regions. This phenomenon could reflect the pathophysiology associated with different IMVM patterns. (orig.)

  14. Region-specific changes in brain diffusivity in fetal isolated mild ventriculomegaly

    International Nuclear Information System (INIS)

    Yaniv, Gal; Katorza, Eldad; Bercovitz, Ronen; Bergman, Dafi; Greenberg, Gahl; Hoffmann, Chen; Biegon, Anat

    2016-01-01

    To evaluate the impact of symmetric and asymmetric isolated mild ventriculomegaly (IMVM, atrial width 10-15 mm) on apparent diffusion coefficient (ADC) values in fetal brain areas. Sixty-seven sequential fetal head magnetic resonance imaging scans (feMRI) of VM cases performed between 2009 and 2014 were compared to 38 normal feMRI scans matched for gestational age (controls). Ultrasound- and MRI-proven IMVM cases were divided into asymmetrical (AVM, ≥2 mm difference in atrial width), symmetrical (SVM, <2 mm difference in atrial width), and asymmetrical IMVM with one normal-sized ventricle (AV1norm). ADC values were significantly elevated in the basal ganglia (BG) of the SVM and AV1norm groups compared to controls (p < 0.004 and p < 0.013, respectively). High diffusivity was constantly detected in the BG ipsilateral to the enlarged atria relative to the normal-sized atria in the AV1norm group (p < 0.03). Frontal lobe ADC values were significantly reduced in the AVM and SVM groups (p < 0.003 and p < 0.003 vs. controls). Temporal lobe ADC values were significantly reduced in the AVM group (p < 0.001 vs. controls). Isolated mild ventriculomegaly is associated with distinct ADC value changes in different brain regions. This phenomenon could reflect the pathophysiology associated with different IMVM patterns. (orig.)

  15. Brain regions associated with the acquisition of conditioned place preference for cocaine vs. social interaction.

    Science.gov (United States)

    El Rawas, Rana; Klement, Sabine; Kummer, Kai K; Fritz, Michael; Dechant, Georg; Saria, Alois; Zernig, Gerald

    2012-01-01

    Positive social interaction could play an essential role in switching the preference of the substance dependent individual away from drug related activities. We have previously shown that conditioned place preference (CPP) for cocaine at the dose of 15 mg/kg and CPP for four 15-min episodes of social interaction were equally strong when rats were concurrently conditioned for place preference by pairing cocaine with one compartment and social interaction with the other. The aim of the present study was to investigate the differential activation of brain regions related to the reward circuitry after acquisition/expression of cocaine CPP or social interaction CPP. Our findings indicate that cocaine CPP and social interaction CPP activated almost the same brain regions. However, the granular insular cortex and the dorsal part of the agranular insular cortex were more activated after cocaine CPP, whereas the prelimbic cortex and the core subregion of the nucleus accumbens were more activated after social interaction CPP. These results suggest that the insular cortex appears to be potently activated after drug conditioning learning while activation of the prelimbic cortex-nucleus accumbens core projection seems to be preferentially involved in the conditioning to non-drug stimuli such as social interaction.

  16. Biochemical responses to dietary α-linolenic acid restriction proceed differently among brain regions in mice.

    Science.gov (United States)

    Miyazawa, Daisuke; Yasui, Yuko; Yamada, Kazuyo; Ohara, Naoki; Okuyama, Harumi

    2011-08-01

    Previously, we noted that the dietary restriction of α-linolenic acid (ALA, n-3) for 4 weeks after weaning brought about significant decreases in the BDNF content and p38 MAPK activity in the striatum of mice, but not in the other regions of the brain, compared with an ALA- and linoleic acid (LNA, n-6)-adequate diet. In this study, we examined whether a prolonged dietary manipulation induces biochemical changes in other regions of the brain as well. Mice were fed a safflower oil (SAF) diet (ALA-restricted, LNA-adequate) or a perilla oil (PER) diet (containing adequate amounts of ALA and LNA) for 8 weeks from weaning. The docosahexaenoic acid (DHA, 22:6n-3) contents and p38 MAPK activities in the cerebral cortex, striatum and hippocampus were significantly lower in the SAF group. The BDNF contents and protein kinase C (PKC) activities in the cerebral cortex as well as in the striatum, but not in the hippocampus, were significantly lower in the SAF group. These data indicate that the biochemical changes induced by the dietary restriction of ALA have a time lag in the striatum and cortex, suggesting that the signal is transmitted through decreased p38 MAPK activity and BDNF content and ultimately decreased PKC activity.

  17. Interactions of early adversity with stress-related gene polymorphisms impact regional brain structure in females.

    Science.gov (United States)

    Gupta, Arpana; Labus, Jennifer; Kilpatrick, Lisa A; Bonyadi, Mariam; Ashe-McNalley, Cody; Heendeniya, Nuwanthi; Bradesi, Sylvie; Chang, Lin; Mayer, Emeran A

    2016-04-01

    Early adverse life events (EALs) have been associated with regional thinning of the subgenual cingulate cortex (sgACC), a brain region implicated in the development of disorders of mood and affect, and often comorbid functional pain disorders, such as irritable bowel syndrome (IBS). Regional neuroinflammation related to chronic stress system activation has been suggested as a possible mechanism underlying these neuroplastic changes. However, the interaction of genetic and environmental factors in these changes is poorly understood. The current study aimed to evaluate the interactions of EALs and candidate gene polymorphisms in influencing thickness of the sgACC. 210 female subjects (137 healthy controls; 73 IBS) were genotyped for stress and inflammation-related gene polymorphisms. Genetic variation with EALs, and diagnosis on sgACC thickness was examined, while controlling for race, age, and total brain volume. Compared to HCs, IBS had significantly reduced sgACC thickness (p = 0.03). Regardless of disease group (IBS vs. HC), thinning of the left sgACC was associated with a significant gene-gene environment interaction between the IL-1β genotype, the NR3C1 haplotype, and a history of EALs (p = 0.05). Reduced sgACC thickness in women with the minor IL-1β allele, was associated with EAL total scores regardless of NR3C1 haplotype status (p = 0.02). In subjects homozygous for the major IL-1β allele, reduced sgACC with increasing levels of EALs was seen only with the less common NR3C1 haplotype (p = 0.02). These findings support an interaction between polymorphisms related to stress and inflammation and early adverse life events in modulating a key region of the emotion arousal circuit.

  18. Chronic microelectrode investigations of normal human brain physiology using a hybrid depth electrode.

    Science.gov (United States)

    Howard, M A; Volkov, I O; Noh, M D; Granner, M A; Mirsky, R; Garell, P C

    1997-01-01

    Neurosurgeons have unique access to in vivo human brain tissue, and in the course of clinical treatment important scientific advances have been made that further our understanding of normal brain physiology. In the modern era, microelectrode recordings have been used to systematically investigate the cellular properties of lateral temporal cerebral cortex. The current report describes a hybrid depth electrode (HDE) recording technique that was developed to enable neurosurgeons to simultaneously investigate normal cellular physiology during chronic intracranial EEG recordings. The HDE combines microelectrode and EEG recordings sites on a single shaft. Multiple microelectrode recordings are obtained from MRI defined brain sites and single-unit activity is discriminated from these data. To date, over 60 HDEs have been placed in 20 epilepsy surgery patients. Unique physiologic data have been gathered from neurons in numerous brain regions, including amygdala, hippocampus, frontal lobe, insula and Heschl's gyrus. Functional activation studies were carried out without risking patient safety or comfort.

  19. Estimating direction in brain-behavior interactions: Proactive and reactive brain states in driving.

    Science.gov (United States)

    Garcia, Javier O; Brooks, Justin; Kerick, Scott; Johnson, Tony; Mullen, Tim R; Vettel, Jean M

    2017-04-15

    Conventional neuroimaging analyses have ascribed function to particular brain regions, exploiting the power of the subtraction technique in fMRI and event-related potential analyses in EEG. Moving beyond this convention, many researchers have begun exploring network-based neurodynamics and coordination between brain regions as a function of behavioral parameters or environmental statistics; however, most approaches average evoked activity across the experimental session to study task-dependent networks. Here, we examined on-going oscillatory activity as measured with EEG and use a methodology to estimate directionality in brain-behavior interactions. After source reconstruction, activity within specific frequency bands (delta: 2-3Hz; theta: 4-7Hz; alpha: 8-12Hz; beta: 13-25Hz) in a priori regions of interest was linked to continuous behavioral measurements, and we used a predictive filtering scheme to estimate the asymmetry between brain-to-behavior and behavior-to-brain prediction using a variant of Granger causality. We applied this approach to a simulated driving task and examined directed relationships between brain activity and continuous driving performance (steering behavior or vehicle heading error). Our results indicated that two neuro-behavioral states may be explored with this methodology: a Proactive brain state that actively plans the response to the sensory information and is characterized by delta-beta activity, and a Reactive brain state that processes incoming information and reacts to environmental statistics primarily within the alpha band. Published by Elsevier Inc.

  20. Source space analysis of event-related dynamic reorganization of brain networks.

    Science.gov (United States)

    Ioannides, Andreas A; Dimitriadis, Stavros I; Saridis, George A; Voultsidou, Marotesa; Poghosyan, Vahe; Liu, Lichan; Laskaris, Nikolaos A

    2012-01-01

    How the brain works is nowadays synonymous with how different parts of the brain work together and the derivation of mathematical descriptions for the functional connectivity patterns that can be objectively derived from data of different neuroimaging techniques. In most cases static networks are studied, often relying on resting state recordings. Here, we present a quantitative study of dynamic reconfiguration of connectivity for event-related experiments. Our motivation is the development of a methodology that can be used for personalized monitoring of brain activity. In line with this motivation, we use data with visual stimuli from a typical subject that participated in different experiments that were previously analyzed with traditional methods. The earlier studies identified well-defined changes in specific brain areas at specific latencies related to attention, properties of stimuli, and tasks demands. Using a recently introduced methodology, we track the event-related changes in network organization, at source space level, thus providing a more global and complete view of the stages of processing associated with the regional changes in activity. The results suggest the time evolving modularity as an additional brain code that is accessible with noninvasive means and hence available for personalized monitoring and clinical applications.

  1. Regional cerebral blood flow and brain atrophy in senile dementia of Alzheimer type (SDAT). Comparing with multi-infarct dementia (MID), and aged control

    Energy Technology Data Exchange (ETDEWEB)

    Okada, K; Kobayashi, S; Yamaguchi, S; Kitani, M; Tsunematsu, T

    1987-05-01

    To investigate the relationship between the reduction of cerebal blood flow and brain atrophy in SDAT, these were measured in 13 cases of senile dementia of Alzheimer type, and compared to 15 cases of multi-infarct Dementia, 39 cases of lacunar infarction without dementia (non-demented CVD group) and 69 cases of aged normal control. Brain atrophy was evaluated by two-dimensional method on CT film by digitizer and regional cerebral blood flow (rCBF) was measured by /sup 133/Xe inhalation method. The degree of brain atrophy in SDAT was almost similar of that of MID. But it was more severe than that of non-demented group. MID showed the lowest rCBF among these groups. SDAT showed significantly lower rCBF than that of aged control, but rCBF in SDAT was equal to that of lacunar stroke without dementia. Focal reduction of cerebral blood flow in bilateral fronto-parietal and left occipital regions were observed in SDAT. Verbal intelligence score (Hasegawa's score) correlated with rCBF and brain atrophy index in MID, and a tendency of correlation between rCBF and brain atrophy in MID was also observed. However, there was no correlation among those indices in SDAT. These findings suggest that the loss of brain substance dose not correspond to the reduction of rCBF in SDAT and simultaneous measurement of rCBF and brain atrophy was useful to differ SDAT from MID.

  2. Brain activities associated with gaming urge of online gaming addiction.

    Science.gov (United States)

    Ko, Chih-Hung; Liu, Gin-Chung; Hsiao, Sigmund; Yen, Ju-Yu; Yang, Ming-Jen; Lin, Wei-Chen; Yen, Cheng-Fang; Chen, Cheng-Sheng

    2009-04-01

    The aim of this study was to identify the neural substrates of online gaming addiction through evaluation of the brain areas associated with the cue-induced gaming urge. Ten participants with online gaming addiction and 10 control subjects without online gaming addiction were tested. They were presented with gaming pictures and the paired mosaic pictures while undergoing functional magnetic resonance imaging (fMRI) scanning. The contrast in blood-oxygen-level dependent (BOLD) signals when viewing gaming pictures and when viewing mosaic pictures was calculated with the SPM2 software to evaluate the brain activations. Right orbitofrontal cortex, right nucleus accumbens, bilateral anterior cingulate and medial frontal cortex, right dorsolateral prefrontal cortex, and right caudate nucleus were activated in the addicted group in contrast to the control group. The activation of the region-of-interest (ROI) defined by the above brain areas was positively correlated with self-reported gaming urge and recalling of gaming experience provoked by the WOW pictures. The results demonstrate that the neural substrate of cue-induced gaming urge/craving in online gaming addiction is similar to that of the cue-induced craving in substance dependence. The above-mentioned brain regions have been reported to contribute to the craving in substance dependence, and here we show that the same areas were involved in online gaming urge/craving. Thus, the results suggest that the gaming urge/craving in online gaming addiction and craving in substance dependence might share the same neurobiological mechanism.

  3. Regional oligodendrocytopathy and astrocytopathy precede myelin loss and blood-brain barrier disruption in a murine model of osmotic demyelination syndrome.

    Science.gov (United States)

    Bouchat, Joanna; Couturier, Bruno; Marneffe, Catherine; Gankam-Kengne, Fabrice; Balau, Benoît; De Swert, Kathleen; Brion, Jean-Pierre; Poncelet, Luc; Gilloteaux, Jacques; Nicaise, Charles

    2018-03-01

    The osmotic demyelination syndrome (ODS) is a non-primary inflammatory disorder of the central nervous system myelin that is often associated with a precipitous rise of serum sodium concentration. To investigate the physiopathology of ODS in vivo, we generated a novel murine model based on the abrupt correction of chronic hyponatremia. Accordingly, ODS mice developed impairments in brainstem auditory evoked potentials and in grip strength. At 24 hr post-correction, oligodendrocyte markers (APC and Cx47) were downregulated, prior to any detectable demyelination. Oligodendrocytopathy was temporally and spatially correlated with the loss of astrocyte markers (ALDH1L1 and Cx43), and both with the brain areas that will develop demyelination. Oligodendrocytopathy and astrocytopathy were confirmed at the ultrastructural level and culminated with necroptotic cell death, as demonstrated by pMLKL immunoreactivity. At 48 hr post-correction, ODS brains contained pathognomonic demyelinating lesions in the pons, mesencephalon, thalamus and cortical regions. These damages were accompanied by blood-brain barrier (BBB) leakages. Expression levels of IL-1β, FasL, TNFRSF6 and LIF factors were significantly upregulated in the ODS lesions. Quiescent microglial cells type A acquired an activated type B morphology within 24 hr post-correction, and reached type D at 48 hr. In conclusion, this murine model of ODS reproduces the CNS demyelination observed in human pathology and indicates ambiguous causes that is regional vulnerability of oligodendrocytes and astrocytes, while it discards BBB disruption as a primary cause of demyelination. This study also raises new queries about the glial heterogeneity in susceptible brain regions as well as about the early microglial activation associated with ODS. © 2017 Wiley Periodicals, Inc.

  4. Spatial patterns of progressive brain volume loss after moderate-severe traumatic brain injury

    Science.gov (United States)

    Jolly, Amy; de Simoni, Sara; Bourke, Niall; Patel, Maneesh C; Scott, Gregory; Sharp, David J

    2018-01-01

    Abstract Traumatic brain injury leads to significant loss of brain volume, which continues into the chronic stage. This can be sensitively measured using volumetric analysis of MRI. Here we: (i) investigated longitudinal patterns of brain atrophy; (ii) tested whether atrophy is greatest in sulcal cortical regions; and (iii) showed how atrophy could be used to power intervention trials aimed at slowing neurodegeneration. In 61 patients with moderate-severe traumatic brain injury (mean age = 41.55 years ± 12.77) and 32 healthy controls (mean age = 34.22 years ± 10.29), cross-sectional and longitudinal (1-year follow-up) brain structure was assessed using voxel-based morphometry on T1-weighted scans. Longitudinal brain volume changes were characterized using a novel neuroimaging analysis pipeline that generates a Jacobian determinant metric, reflecting spatial warping between baseline and follow-up scans. Jacobian determinant values were summarized regionally and compared with clinical and neuropsychological measures. Patients with traumatic brain injury showed lower grey and white matter volume in multiple brain regions compared to controls at baseline. Atrophy over 1 year was pronounced following traumatic brain injury. Patients with traumatic brain injury lost a mean (± standard deviation) of 1.55% ± 2.19 of grey matter volume per year, 1.49% ± 2.20 of white matter volume or 1.51% ± 1.60 of whole brain volume. Healthy controls lost 0.55% ± 1.13 of grey matter volume and gained 0.26% ± 1.11 of white matter volume; equating to a 0.22% ± 0.83 reduction in whole brain volume. Atrophy was greatest in white matter, where the majority (84%) of regions were affected. This effect was independent of and substantially greater than that of ageing. Increased atrophy was also seen in cortical sulci compared to gyri. There was no relationship between atrophy and time since injury or age at baseline. Atrophy rates were related to memory performance at the end of the

  5. Effects of bilingualism on vocabulary, executive functions, age of dementia onset, and regional brain structure.

    Science.gov (United States)

    Gasquoine, Philip Gerard

    2016-11-01

    To review the current literature on the effects of bilingualism on vocabulary, executive functions, age of dementia onset, and regional brain structure. PubMed and PsycINFO databases were searched (from January 1999 to present) for relevant original research and review articles on bilingualism (but not multilingualism) paired with each target neuropsychological variable published in English. A qualitative review of these articles was conducted. It has long been known that mean scores of bilinguals fall below those of monolinguals on vocabulary and other language, but not visual-perceptual, format cognitive tests. Contemporary studies that have reported higher mean scores for bilinguals than monolinguals on executive function task-switching or inhibition tasks have not always been replicated, leading to concerns of publication bias, statistical flaws, and failures to match groups on potentially confounding variables. Studies suggesting the onset of Alzheimer's disease occurred about 4 years later for bilinguals versus monolinguals have not been confirmed in longitudinal, cohort, community-based, incidence studies that have used neuropsychological testing and diagnostic criteria to establish an age of dementia diagnosis. Neuroimaging studies of regional gray and white matter volume in bilinguals versus monolinguals show inconsistencies in terms of both the regions of difference and the nature of the difference. Resolving inconsistencies in the behavioral data is necessary before searching in the brain for neuroanatomical correlation. Comparisons of balanced versus language-dominant groups within the same ethnoculture combined with objective measurement of bilingualism could better match groups on potentially confounding variables. (PsycINFO Database Record (c) 2016 APA, all rights reserved).

  6. Using Individualized Brain Network for Analyzing Structural Covariance of the Cerebral Cortex in Alzheimer's Patients.

    Science.gov (United States)

    Kim, Hee-Jong; Shin, Jeong-Hyeon; Han, Cheol E; Kim, Hee Jin; Na, Duk L; Seo, Sang Won; Seong, Joon-Kyung

    2016-01-01

    Cortical thinning patterns in Alzheimer's disease (AD) have been widely reported through conventional regional analysis. In addition, the coordinated variance of cortical thickness in different brain regions has been investigated both at the individual and group network levels. In this study, we aim to investigate network architectural characteristics of a structural covariance network (SCN) in AD, and further to show that the structural covariance connectivity becomes disorganized across the brain regions in AD, while the normal control (NC) subjects maintain more clustered and consistent coordination in cortical atrophy variations. We generated SCNs directly from T1-weighted MR images of individual patients using surface-based cortical thickness data, with structural connectivity defined as similarity in cortical thickness within different brain regions. Individual SCNs were constructed using morphometric data from the Samsung Medical Center (SMC) dataset. The structural covariance connectivity showed higher clustering than randomly generated networks, as well as similar minimum path lengths, indicating that the SCNs are "small world." There were significant difference between NC and AD group in characteristic path lengths (z = -2.97, p < 0.01) and small-worldness values (z = 4.05, p < 0.01). Clustering coefficients in AD was smaller than that of NC but there was no significant difference (z = 1.81, not significant). We further observed that the AD patients had significantly disrupted structural connectivity. We also show that the coordinated variance of cortical thickness is distributed more randomly from one region to other regions in AD patients when compared to NC subjects. Our proposed SCN may provide surface-based measures for understanding interaction between two brain regions with co-atrophy of the cerebral cortex due to normal aging or AD. We applied our method to the AD Neuroimaging Initiative (ADNI) data to show consistency in results with the SMC

  7. The V1-V3 region of a brain-derived HIV-1 envelope glycoprotein determines macrophage tropism, low CD4 dependence, increased fusogenicity and altered sensitivity to entry inhibitors

    Directory of Open Access Journals (Sweden)

    Martín-García Julio

    2008-10-01

    Full Text Available Abstract Background HIV-1 infects macrophages and microglia in the brain and can cause neurological disorders in infected patients. We and others have shown that brain-derived envelope glycoproteins (Env have lower CD4 dependence and higher avidity for CD4 than those from peripheral isolates, and we have also observed increased fusogenicity and reduced sensitivity to the fusion inhibitor T-1249. Due to the genetic differences between brain and spleen env from one individual throughout gp120 and in gp41's heptad repeat 2 (HR2, we investigated the viral determinants for the phenotypic differences by performing functional studies with chimeric and mutant Env. Results Chimeric Env showed that the V1/V2-C2-V3 region in brain's gp120 determines the low CD4 dependence and high avidity for CD4, as well as macrophage tropism and reduced sensitivity to the small molecule BMS-378806. Changes in brain gp41's HR2 region did not contribute to the increased fusogenicity or to the reduced sensitivity to T-1249, since a T-1249-based peptide containing residues found in brain's but not in spleen's HR2 had similar potency than T-1249 and interacted similarly with an immobilized heptad repeat 1-derived peptide in surface plasmon resonance analysis. However, the increased fusogenicity and reduced T-1249 sensitivity of brain and certain chimeric Env mostly correlated with the low CD4 dependence and high avidity for CD4 determined by brain's V1-V3 region. Remarkably, most but not all of these low CD4-dependent, macrophage tropic envelopes glycoproteins also had increased sensitivity to the novel allosteric entry inhibitor HNG-105. The gp120's C2 region asparagine 283 (N283 has been previously associated with macrophage tropism, brain infection, lower CD4 dependence and higher CD4 affinity. Therefore, we introduced the N283T mutation into an env clone from a brain-derived isolate and into a brain tissue-derived env clone, and the T283N change into a spleen-derived env

  8. Implementation of a computer-aided detection tool for quantification of intracranial radiologic markers on brain CT images

    Science.gov (United States)

    Aghaei, Faranak; Ross, Stephen R.; Wang, Yunzhi; Wu, Dee H.; Cornwell, Benjamin O.; Ray, Bappaditya; Zheng, Bin

    2017-03-01

    Aneurysmal subarachnoid hemorrhage (aSAH) is a form of hemorrhagic stroke that affects middle-aged individuals and associated with significant morbidity and/or mortality especially those presenting with higher clinical and radiologic grades at the time of admission. Previous studies suggested that blood extravasated after aneurysmal rupture was a potentially clinical prognosis factor. But all such studies used qualitative scales to predict prognosis. The purpose of this study is to develop and test a new interactive computer-aided detection (CAD) tool to detect, segment and quantify brain hemorrhage and ventricular cerebrospinal fluid on non-contrasted brain CT images. First, CAD segments brain skull using a multilayer region growing algorithm with adaptively adjusted thresholds. Second, CAD assigns pixels inside the segmented brain region into one of three classes namely, normal brain tissue, blood and fluid. Third, to avoid "black-box" approach and increase accuracy in quantification of these two image markers using CT images with large noise variation in different cases, a graphic User Interface (GUI) was implemented and allows users to visually examine segmentation results. If a user likes to correct any errors (i.e., deleting clinically irrelevant blood or fluid regions, or fill in the holes inside the relevant blood or fluid regions), he/she can manually define the region and select a corresponding correction function. CAD will automatically perform correction and update the computed data. The new CAD tool is now being used in clinical and research settings to estimate various quantitatively radiological parameters/markers to determine radiological severity of aSAH at presentation and correlate the estimations with various homeostatic/metabolic derangements and predict clinical outcome.

  9. Regional brain volumes, diffusivity, and metabolite changes after electroconvulsive therapy for severe depression

    DEFF Research Database (Denmark)

    Jørgensen, A.; Magnusson, P.; Hanson, Lars G.

    2016-01-01

    , and metabolite changes in 19 patients receiving ECT for severe depression. Other regions of interest included the amygdala, dorsolateral prefrontal cortex (DLPFC), orbitofrontal cortex, and hypothalamus. Patients received a 3T MR scan before ECT (TP1), 1 week (TP2), and 4 weeks (TP3) after ECT. Results......: Hippocampal and amygdala volume increased significantly at TP2 and continued to be increased at TP3. DLPFC exhibited a transient volume reduction at TP2. DTI revealed a reduced anisotropy and diffusivity of the hippocampus at TP2. We found no significant post-ECT changes in brain metabolite concentrations...

  10. Predicting human age using regional morphometry and inter-regional morphological similarity

    Science.gov (United States)

    Wang, Xun-Heng; Li, Lihua

    2016-03-01

    The goal of this study is predicting human age using neuro-metrics derived from structural MRI, as well as investigating the relationships between age and predictive neuro-metrics. To this end, a cohort of healthy subjects were recruited from 1000 Functional Connectomes Project. The ages of the participations were ranging from 7 to 83 (36.17+/-20.46). The structural MRI for each subject was preprocessed using FreeSurfer, resulting in regional cortical thickness, mean curvature, regional volume and regional surface area for 148 anatomical parcellations. The individual age was predicted from the combination of regional and inter-regional neuro-metrics. The prediction accuracy is r = 0.835, p Pearson correlation coefficient between predicted ages and actual ages. Moreover, the LASSO linear regression also found certain predictive features, most of which were inter-regional features. The turning-point of the developmental trajectories in human brain was around 40 years old based on regional cortical thickness. In conclusion, structural MRI could be potential biomarkers for the aging in human brain. The human age could be successfully predicted from the combination of regional morphometry and inter-regional morphological similarity. The inter-regional measures could be beneficial to investigating human brain connectome.

  11. Gender Differences in Regional Brain Activity in Patients with Chronic Primary Insomnia: Evidence from a Resting-State fMRI Study.

    Science.gov (United States)

    Dai, Xi-Jian; Nie, Xiao; Liu, Xuming; Pei, Li; Jiang, Jian; Peng, De-chang; Gong, Hong-Han; Zeng, Xian-Jun; Wáng, Yì-Xiáng J; Zhan, Yang

    2016-03-01

    To explore the regional brain activities in patients with chronic primary insomnia (PCPIs) and their sex differences. Forty-two PCPIs (27 females, 15 males) and 42 good sleepers (GSs; 24 females, 18 males) were recruited. Six PCPIs (3 males, 3 females) were scanned twice by MRI to examine the test-retest reliability. Amplitude of low frequency fluctuation (ALFF) method was used to assess the local brain features. The mean signal values of the different ALFF areas were analyzed with a receiver operating characteristic (ROC) curve. Simple linear regression analysis was performed to investigate the relationships between clinical features and different brain areas. Both female and male PCPIs showed higher ALFF in the temporal lobe and occipital lobe, especially in female PCPIs. Female PCPIs had lower ALFF in the bilateral cerebellum posterior lobe, left dorsolateral prefrontal cortex, and bilateral limbic lobe; however, male PCPIs showed lower ALFF in the left occipital gyrus. The mean signal value of the cerebellum in female PCPIs showed negative correlations with negative emotions. Compared with male PCPIs, female PCPIs showed higher ALFF in the bilateral middle temporal gyrus and lower ALFF in the left limbic lobe. The different areas showed high test-retest stability (Clusters of contiguous volumes ≥ 1080 mm(3) with an intraclass correlation coefficient ≥ 0.80) and high degree of sensitivity and specificity. Female PCPIs showed more regional brain differences with higher and lower ALFF responses than male PCPIs. However, they shared analogous excessive hyperarousal mechanism and wide variations in aberrant brain areas. © 2016 American Academy of Sleep Medicine.

  12. Ontogenetic Shape Change in the Chicken Brain: Implications for Paleontology.

    Directory of Open Access Journals (Sweden)

    Soichiro Kawabe

    Full Text Available Paleontologists have investigated brain morphology of extinct birds with little information on post-hatching changes in avian brain morphology. Without the knowledge of ontogenesis, assessing brain morphology in fossil taxa could lead to misinterpretation of the phylogeny or neurosensory development of extinct species. Hence, it is imperative to determine how avian brain morphology changes during post-hatching growth. In this study, chicken brain shape was compared at various developmental stages using three-dimensional (3D geometric morphometric analysis and the growth rate of brain regions was evaluated to explore post-hatching morphological changes. Microscopic MRI (μMRI was used to acquire in vivo data from living and post-mortem chicken brains. The telencephalon rotates caudoventrally during growth. This change in shape leads to a relative caudodorsal rotation of the cerebellum and myelencephalon. In addition, all brain regions elongate rostrocaudally and this leads to a more slender brain shape. The growth rates of each brain region were constant and the slopes from the growth formula were parallel. The dominant pattern of ontogenetic shape change corresponded with interspecific shape changes due to increasing brain size. That is, the interspecific and ontogenetic changes in brain shape due to increased size have similar patterns. Although the shape of the brain and each brain region changed considerably, the volume ratio of each brain region did not change. This suggests that the brain can change its shape after completing functional differentiation of the brain regions. Moreover, these results show that consideration of ontogenetic changes in brain shape is necessary for an accurate assessment of brain morphology in paleontological studies.

  13. Effect of aging on alpha-1 adrenergic stimulation of phosphoinositide hydrolysis in various regions of rat brain

    International Nuclear Information System (INIS)

    Burnett, D.M.; Bowyer, J.F.; Masserano, J.M.; Zahniser, N.R.

    1990-01-01

    The effects of aging were examined on the ability of alpha-1 adrenergic receptor agonists to stimulate phosphoinositide hydrolysis in three brain regions. Tissue minces of thalamus, cerebral cortex and hippocampus from 3-, 18- and 28-month-old male Fischer 344 rats were prelabeled with [ 3 H]myoinositol. Exposure of these prelabeled minces to phenylephrine and (-)-norepinephrine revealed that accumulation of [ 3 H]inositol phosphates was selectively reduced by 20 to 30% in the thalamus and cerebral cortex of the oldest age group. Analysis of concentration-response and competition binding curves indicated that this decrease was due to diminished agonist efficacy rather than diminished receptor affinity. The reduction in responsiveness to phenylephrine and (-)-norepinephrine in the cerebral cortex and the lack of any changes in the hippocampus parallel previously reported changes in the density of alpha-1 adrenergic receptors with aging. These data indicate that the ability of alpha-1 adrenergic receptor agonists to stimulate phosphoinositide hydrolysis is reduced in some, but not all, brain regions of aged Fischer 344 rats

  14. Recent technological advances in pediatric brain tumor surgery.

    Science.gov (United States)

    Zebian, Bassel; Vergani, Francesco; Lavrador, José Pedro; Mukherjee, Soumya; Kitchen, William John; Stagno, Vita; Chamilos, Christos; Pettorini, Benedetta; Mallucci, Conor

    2017-01-01

    X-rays and ventriculograms were the first imaging modalities used to localize intracranial lesions including brain tumors as far back as the 1880s. Subsequent advances in preoperative radiological localization included computed tomography (CT; 1971) and MRI (1977). Since then, other imaging modalities have been developed for clinical application although none as pivotal as CT and MRI. Intraoperative technological advances include the microscope, which has allowed precise surgery under magnification and improved lighting, and the endoscope, which has improved the treatment of hydrocephalus and allowed biopsy and complete resection of intraventricular, pituitary and pineal region tumors through a minimally invasive approach. Neuronavigation, intraoperative MRI, CT and ultrasound have increased the ability of the neurosurgeon to perform safe and maximal tumor resection. This may be facilitated by the use of fluorescing agents, which help define the tumor margin, and intraoperative neurophysiological monitoring, which helps identify and protect eloquent brain.

  15. Neuronal survival in the brain: neuron type-specific mechanisms

    DEFF Research Database (Denmark)

    Pfisterer, Ulrich Gottfried; Khodosevich, Konstantin

    2017-01-01

    Neurogenic regions of mammalian brain produce many more neurons that will eventually survive and reach a mature stage. Developmental cell death affects both embryonically produced immature neurons and those immature neurons that are generated in regions of adult neurogenesis. Removal of substantial...... numbers of neurons that are not yet completely integrated into the local circuits helps to ensure that maturation and homeostatic function of neuronal networks in the brain proceed correctly. External signals from brain microenvironment together with intrinsic signaling pathways determine whether...... for survival in a certain brain region. This review focuses on how immature neurons survive during normal and impaired brain development, both in the embryonic/neonatal brain and in brain regions associated with adult neurogenesis, and emphasizes neuron type-specific mechanisms that help to survive for various...

  16. Pro-region engineering for improved yeast display and secretion of brain derived neurotrophic factor.

    Science.gov (United States)

    Burns, Michael L; Malott, Thomas M; Metcalf, Kevin J; Puguh, Arthya; Chan, Jonah R; Shusta, Eric V

    2016-03-01

    Brain derived neurotrophic factor (BDNF) is a promising therapeutic candidate for a variety of neurological diseases. However, it is difficult to produce as a recombinant protein. In its native mammalian context, BDNF is first produced as a pro-protein with subsequent proteolytic removal of the pro-region to yield mature BDNF protein. Therefore, in an attempt to improve yeast as a host for heterologous BDNF production, the BDNF pro-region was first evaluated for its effects on BDNF surface display and secretion. Addition of the wild-type pro-region to yeast BDNF production constructs improved BDNF folding both as a surface-displayed and secreted protein in terms of binding its natural receptors TrkB and p75, but titers remained low. Looking to further enhance the chaperone-like functions provided by the pro-region, two rounds of directed evolution were performed, yielding mutated pro-regions that further improved the display and secretion properties of BDNF. Subsequent optimization of the protease recognition site was used to control whether the produced protein was in pro- or mature BDNF forms. Taken together, we have demonstrated an effective strategy for improving BDNF compatibility with yeast protein engineering and secretion platforms. Copyright © 2015 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  17. Structural brain network analysis in families multiply affected with bipolar I disorder.

    Science.gov (United States)

    Forde, Natalie J; O'Donoghue, Stefani; Scanlon, Cathy; Emsell, Louise; Chaddock, Chris; Leemans, Alexander; Jeurissen, Ben; Barker, Gareth J; Cannon, Dara M; Murray, Robin M; McDonald, Colm

    2015-10-30

    Disrupted structural connectivity is associated with psychiatric illnesses including bipolar disorder (BP). Here we use structural brain network analysis to investigate connectivity abnormalities in multiply affected BP type I families, to assess the utility of dysconnectivity as a biomarker and its endophenotypic potential. Magnetic resonance diffusion images for 19 BP type I patients in remission, 21 of their first degree unaffected relatives, and 18 unrelated healthy controls underwent tractography. With the automated anatomical labelling atlas being used to define nodes, a connectivity matrix was generated for each subject. Network metrics were extracted with the Brain Connectivity Toolbox and then analysed for group differences, accounting for potential confounding effects of age, gender and familial association. Whole brain analysis revealed no differences between groups. Analysis of specific mainly frontal regions, previously implicated as potentially endophenotypic by functional magnetic resonance imaging analysis of the same cohort, revealed a significant effect of group in the right medial superior frontal gyrus and left middle frontal gyrus driven by reduced organisation in patients compared with controls. The organisation of whole brain networks of those affected with BP I does not differ from their unaffected relatives or healthy controls. In discreet frontal regions, however, anatomical connectivity is disrupted in patients but not in their unaffected relatives. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

  18. Spatial patterns of progressive brain volume loss after moderate-severe traumatic brain injury.

    Science.gov (United States)

    Cole, James H; Jolly, Amy; de Simoni, Sara; Bourke, Niall; Patel, Maneesh C; Scott, Gregory; Sharp, David J

    2018-01-04

    Traumatic brain injury leads to significant loss of brain volume, which continues into the chronic stage. This can be sensitively measured using volumetric analysis of MRI. Here we: (i) investigated longitudinal patterns of brain atrophy; (ii) tested whether atrophy is greatest in sulcal cortical regions; and (iii) showed how atrophy could be used to power intervention trials aimed at slowing neurodegeneration. In 61 patients with moderate-severe traumatic brain injury (mean age = 41.55 years ± 12.77) and 32 healthy controls (mean age = 34.22 years ± 10.29), cross-sectional and longitudinal (1-year follow-up) brain structure was assessed using voxel-based morphometry on T1-weighted scans. Longitudinal brain volume changes were characterized using a novel neuroimaging analysis pipeline that generates a Jacobian determinant metric, reflecting spatial warping between baseline and follow-up scans. Jacobian determinant values were summarized regionally and compared with clinical and neuropsychological measures. Patients with traumatic brain injury showed lower grey and white matter volume in multiple brain regions compared to controls at baseline. Atrophy over 1 year was pronounced following traumatic brain injury. Patients with traumatic brain injury lost a mean (± standard deviation) of 1.55% ± 2.19 of grey matter volume per year, 1.49% ± 2.20 of white matter volume or 1.51% ± 1.60 of whole brain volume. Healthy controls lost 0.55% ± 1.13 of grey matter volume and gained 0.26% ± 1.11 of white matter volume; equating to a 0.22% ± 0.83 reduction in whole brain volume. Atrophy was greatest in white matter, where the majority (84%) of regions were affected. This effect was independent of and substantially greater than that of ageing. Increased atrophy was also seen in cortical sulci compared to gyri. There was no relationship between atrophy and time since injury or age at baseline. Atrophy rates were related to memory performance at the end of the follow

  19. Frequency-Dependent Modulation of Regional Synchrony in the Human Brain by Eyes Open and Eyes Closed Resting-States.

    Science.gov (United States)

    Song, Xiaopeng; Zhou, Shuqin; Zhang, Yi; Liu, Yijun; Zhu, Huaiqiu; Gao, Jia-Hong

    2015-01-01

    The eyes-open (EO) and eyes-closed (EC) states have differential effects on BOLD-fMRI signal dynamics, affecting both the BOLD oscillation frequency of a single voxel and the regional homogeneity (ReHo) of several neighboring voxels. To explore how the two resting-states modulate the local synchrony through different frequency bands, we decomposed the time series of each voxel into several components that fell into distinct frequency bands. The ReHo in each of the bands was calculated and compared between the EO and EC conditions. The cross-voxel correlations between the mean frequency and the overall ReHo of each voxel's original BOLD series in different brain areas were also calculated and compared between the two states. Compared with the EC state, ReHo decreased with EO in a wide frequency band of 0.01-0.25 Hz in the bilateral thalamus, sensorimotor network, and superior temporal gyrus, while ReHo increased significantly in the band of 0-0.01 Hz in the primary visual cortex, and in a higher frequency band of 0.02-0.1 Hz in the higher order visual areas. The cross-voxel correlations between the frequency and overall ReHo were negative in all the brain areas but varied from region to region. These correlations were stronger with EO in the visual network and the default mode network. Our results suggested that different frequency bands of ReHo showed different sensitivity to the modulation of EO-EC states. The better spatial consistency between the frequency and overall ReHo maps indicated that the brain might adopt a stricter frequency-dependent configuration with EO than with EC.

  20. On development of functional brain connectivity in the young brain

    Directory of Open Access Journals (Sweden)

    G.E. Anna-Jasmijn eHoff

    2013-10-01

    Full Text Available Our brain is a complex network of structurally and functionally interconnected regions, shaped to efficiently process and integrate information. The development from a brain equipped with basic functionalities to an efficient network facilitating complex behavior starts during gestation and continues into adulthood. Resting-state functional MRI (rs-fMRI enables the examination of developmental aspects of functional connectivity and functional brain networks. This review will discuss changes observed in the developing brain on the level of network functional connectivity (FC from a gestational age of 20 weeks onwards. We discuss findings of resting-state fMRI studies showing that functional network development starts during gestation, creating a foundation for each of the resting-state networks to be established. Visual and sensorimotor areas are reported to develop first, with other networks, at different rates, increasing both in network connectivity and size over time. Reaching childhood, marked fine-tuning and specialization takes place in the regions necessary for higher-order cognitive functions.