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Sample records for defined brain regions

  1. Reduction of variance in measurements of average metabolite concentration in anatomically-defined brain regions

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    Larsen, Ryan J.; Newman, Michael; Nikolaidis, Aki

    2016-11-01

    Multiple methods have been proposed for using Magnetic Resonance Spectroscopy Imaging (MRSI) to measure representative metabolite concentrations of anatomically-defined brain regions. Generally these methods require spectral analysis, quantitation of the signal, and reconciliation with anatomical brain regions. However, to simplify processing pipelines, it is practical to only include those corrections that significantly improve data quality. Of particular importance for cross-sectional studies is knowledge about how much each correction lowers the inter-subject variance of the measurement, thereby increasing statistical power. Here we use a data set of 72 subjects to calculate the reduction in inter-subject variance produced by several corrections that are commonly used to process MRSI data. Our results demonstrate that significant reductions of variance can be achieved by performing water scaling, accounting for tissue type, and integrating MRSI data over anatomical regions rather than simply assigning MRSI voxels with anatomical region labels.

  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. Defining nodes in complex brain networks.

    Science.gov (United States)

    Stanley, Matthew L; Moussa, Malaak N; Paolini, Brielle M; Lyday, Robert G; Burdette, Jonathan H; Laurienti, Paul J

    2013-11-22

    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 deserves extensive

  4. Brain Region Mapping using Global Metabolomics

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    Ivanisevic, Julijana; Epstein, Adrian; Kurczy, Michael E.; Benton, H. Paul; Uritboonthai, Winnie; Fox, Howard S.; Boska, Michael D.; Gendelman, Howard E.; Siuzdak, Gary

    2014-01-01

    SUMMARY Historically, studies of brain metabolism have been based on targeted analyses of a limited number of metabolites. Here we present a novel untargeted mass spectrometry-based metabolomics approach that has successfully uncovered differences in broad array of metabolites across anatomical regions of the mouse brain. The NSG immunodeficient mouse model was chosen because of its ability to undergo humanization leading to numerous applications in oncology and infectious disease research. Metabolic phenotyping by hydrophilic interaction liquid chromatography and nanostructure imaging mass spectrometry revealed unique water-soluble and lipid metabolite patterns between brain regions. Neurochemical differences in metabolic phenotypes were mainly defined by various phospholipids and several intriguing metabolites including carnosine, cholesterol sulfate, lipoamino acids, uric and sialic acid whose physiological roles in brain metabolism are poorly understood. This study lays important groundwork by defining regional homeostasis for the normal mouse brain to give context to the reaction to pathological events. PMID:25457182

  5. Toward defining the anatomo-proteomic puzzle of the human brain: An integrative analysis.

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    Fernandez-Irigoyen, Joaquín; Labarga, Alberto; Zabaleta, Aintzane; de Morentin, Xabier Martínez; Perez-Valderrama, Estela; Zelaya, María Victoria; Santamaria, Enrique

    2015-10-01

    The human brain is exceedingly complex, constituted by billions of neurons and trillions of synaptic connections that, in turn, define ∼900 neuroanatomical subdivisions in the adult brain (Hawrylycz et al. An anatomically comprehensive atlas of the human brain transcriptome. Nature 2012, 489, 391-399). The human brain transcriptome has revealed specific regional transcriptional signatures that are regulated in a spatiotemporal manner, increasing the complexity of the structural and molecular organization of this organ (Kang et al. Spatio-temporal transcriptome of the human brain. Nature 2011, 478, 483-489). During the last decade, neuroproteomics has emerged as a powerful approach to profile neural proteomes using shotgun-based MS, providing complementary information about protein content and function at a global level. Here, we revise recent proteome profiling studies performed in human brain, with special emphasis on proteome mapping of anatomical macrostructures, specific subcellular compartments, and cerebrospinal fluid. Moreover, we have performed an integrative functional analysis of the protein compilation derived from these large-scale human brain proteomic studies in order to obtain a comprehensive view of human brain biology. Finally, we also discuss the potential contribution of our meta-analysis to the Chromosome-centric Human Proteome Project initiative. © 2014 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  6. Regional brain hypometabolism is unrelated to regional amyloid plaque burden

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    Altmann, Andre; Ng, Bernard; Landau, Susan M.; Jagust, William J.

    2015-01-01

    See Sorg and Grothe (doi:10.1093/brain/awv302) for a scientific commentary on this article. In its original form, the amyloid cascade hypothesis of Alzheimer’s disease holds that fibrillar deposits of amyloid are an early, driving force in pathological events leading ultimately to neuronal death. Early clinicopathological investigations highlighted a number of inconsistencies leading to an updated hypothesis in which amyloid plaques give way to amyloid oligomers as the driving force in pathogenesis. Rather than focusing on the inconsistencies, amyloid imaging studies have tended to highlight the overlap between regions that show early amyloid plaque signal on positron emission tomography and that also happen to be affected early in Alzheimer’s disease. Recent imaging studies investigating the regional dependency between metabolism and amyloid plaque deposition have arrived at conflicting results, with some showing regional associations and other not. We extracted multimodal neuroimaging data from the Alzheimer’s disease neuroimaging database for 227 healthy controls and 434 subjects with mild cognitive impairment. We analysed regional patterns of amyloid deposition, regional glucose metabolism and regional atrophy using florbetapir (18F) positron emission tomography, 18F-fluordeoxyglucose positron emission tomography and T1-weighted magnetic resonance imaging, respectively. Specifically, we derived grey matter density and standardized uptake value ratios for both positron emission tomography tracers in 404 functionally defined regions of interest. We examined the relation between regional glucose metabolism and amyloid plaques using linear models. For each region of interest, correcting for regional grey matter density, age, education and disease status, we tested the association of regional glucose metabolism with (i) cortex-wide florbetapir uptake; (ii) regional (i.e. in the same region of interest) florbetapir uptake; and (iii) regional florbetapir uptake

  7. Defining urban and rural regions by multifractal spectrums of urbanization

    CERN Document Server

    Chen, Yanguang

    2015-01-01

    The spatial pattern of urban-rural regional system is associated with the dynamic process of urbanization. How to characterize the urban-rural terrain using quantitative measurement is a difficult problem remaining to be solved. This paper is devoted to defining urban and rural regions using ideas from fractals. A basic postulate is that human geographical systems are of self-similar patterns associated with recursive processes. Then multifractal geometry can be employed to describe or define the urban and rural terrain with the level of urbanization. A space-filling index of urban-rural region based on the generalized correlation dimension is presented to reflect the degree of geo-spatial utilization in terms of urbanization. The census data of America and China are adopted to show how to make empirical analyses of urban-rural multifractals. This work is not so much a positive analysis as a normative study, but it proposes a new way of investigating urban and rural regional systems using fractal theory.

  8. Defining Urban and Rural Regions by Multifractal Spectrums of Urbanization

    Science.gov (United States)

    Chen, Yanguang

    2016-03-01

    The spatial pattern of the urban-rural regional system is associated with the dynamic process of urbanization. How to characterize the urban-rural terrain using quantitative measurement is a difficult problem remaining to be solved. This paper is devoted to defining urban and rural regions using ideas from fractals. A basic postulate is that human geographical systems are of self-similar patterns correlated with recursive processes. Then multifractal geometry can be employed to describe or define the urban and rural terrain with the level of urbanization. A space-filling index of urban-rural region based on a generalized correlation dimension is presented to reflect the degree of geo-spatial utilization in terms of urbanism. The census data of America and China are used to show how to make empirical analyses of urban-rural multifractals. This work is a normative study rather than a positive study, and it proposes a new way of investigating urban and rural regional systems using fractal theory.

  9. Defining Scenarios: Linking Integrated Models, Regional Concerns, and Stakeholders

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    Hartmann, H. C.; Stewart, S.; Liu, Y.; Mahmoud, M.

    2007-05-01

    Scenarios are important tools for long-term planning, and there is great interest in using integrated models in scenario studies. However, scenario definition and assessment are creative, as well as scientific, efforts. Using facilitated creative processes, we have worked with stakeholders to define regionally significant scenarios that encompass a broad range of hydroclimatic, socioeconomic, and institutional dimensions. The regional scenarios subsequently inform the definition of local scenarios that work with context-specific integrated models that, individually, can address only a subset of overall regional complexity. Based on concerns of stakeholders in the semi-arid US Southwest, we prioritized three dimensions that are especially important, yet highly uncertain, for long-term planning: hydroclimatic conditions (increased variability, persistent drought), development patterns (urban consolidation, distributed rural development), and the nature of public institutions (stressed, proactive). Linking across real-world decision contexts and integrated modeling efforts poses challenges of creatively connecting the conceptual models held by both the research and stakeholder communities.

  10. Local interneurons define functionally distinct regions within lobster olfactory glomeruli

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    Wachowiak; Diebel; Ache

    1997-01-01

    Whole-cell recording coupled with biocytin injection revealed four types of interneurons intrinsic to the olfactory lobe (OL) of the spiny lobster Panulirus argus. Each type of neuron had a distinct pattern of arborization within the three anatomically defined regions of OL glomeruli (cap, subcap and base). Type I interneurons innervated all three regions, while types II, III and IV branched only in the cap, subcap and base, respectively. Type I interneurons responded to electrical stimulation of the antennular (olfactory) nerve with a burst of 1­20 action potentials and a 1­10 s depolarization. Type II (cap) interneurons responded to the same input with a burst of 1­3 action potentials followed by a shorter hyperpolarization. Type III (subcap) interneurons responded with a burst of 1­6 action potentials followed by a delayed, 0.5­4 s depolarization. Type IV (base) interneurons responded with a brief depolarization or a burst of 1­3 action potentials followed by a 1 s hyperpolarization. The regionalized arborization and the different response properties of the type II, III and IV interneurons strongly imply that lobster olfactory glomeruli contain functionally distinct regions, a feature that should be useful in understanding the multiple synaptic pathways involved in processing olfactory input.

  11. 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.

  12. Selective constraints in experimentally defined primate regulatory regions.

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    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

  13. Automated regional behavioral analysis for human brain images.

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    Lancaster, Jack L; Laird, Angela R; Eickhoff, Simon B; Martinez, Michael J; Fox, P Mickle; Fox, Peter T

    2012-01-01

    Behavioral categories of functional imaging experiments along with standardized brain coordinates of associated activations were used to develop a method to automate regional behavioral analysis of human brain images. Behavioral and coordinate data were taken from the BrainMap database (http://www.brainmap.org/), which documents over 20 years of published functional brain imaging studies. A brain region of interest (ROI) for behavioral analysis can be defined in functional images, anatomical images or brain atlases, if images are spatially normalized to MNI or Talairach standards. Results of behavioral analysis are presented for each of BrainMap's 51 behavioral sub-domains spanning five behavioral domains (Action, Cognition, Emotion, Interoception, and Perception). For each behavioral sub-domain the fraction of coordinates falling within the ROI was computed and compared with the fraction expected if coordinates for the behavior were not clustered, i.e., uniformly distributed. When the difference between these fractions is large behavioral association is indicated. A z-score ≥ 3.0 was used to designate statistically significant behavioral association. The left-right symmetry of ~100K activation foci was evaluated by hemisphere, lobe, and by behavioral sub-domain. Results highlighted the classic left-side dominance for language while asymmetry for most sub-domains (~75%) was not statistically significant. Use scenarios were presented for anatomical ROIs from the Harvard-Oxford cortical (HOC) brain atlas, functional ROIs from statistical parametric maps in a TMS-PET study, a task-based fMRI study, and ROIs from the ten "major representative" functional networks in a previously published resting state fMRI study. Statistically significant behavioral findings for these use scenarios were consistent with published behaviors for associated anatomical and functional regions.

  14. Normalized regional brain atrophy measurements in multiple sclerosis

    Energy Technology Data Exchange (ETDEWEB)

    Zivadinov, Robert; Locatelli, Laura; Stival, Barbara; Bratina, Alessio; Nasuelli, Davide; Zorzon, Marino [Department of Clinical Medicine and Neurology, Cattinara Hospital, University of Trieste, Strada di Fiume, 447-34149, Trieste (Italy); Grop, Attilio [Department of Electrical, Electronics and Computer Science, University of Trieste, Trieste (Italy); Brnabic-Razmilic, Ozana [Statistical Analysis Centre, Heilbronn (Germany)

    2003-11-01

    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

  15. Variance in brain volume with advancing age: implications for defining the limits of normality.

    Directory of Open Access Journals (Sweden)

    David Alexander Dickie

    Full Text Available Statistical models of normal ageing brain tissue volumes may support earlier diagnosis of increasingly common, yet still fatal, neurodegenerative diseases. For example, the statistically defined distribution of normal ageing brain tissue volumes may be used as a reference to assess patient volumes. To date, such models were often derived from mean values which were assumed to represent the distributions and boundaries, i.e. percentile ranks, of brain tissue volume. Since it was previously unknown, the objective of the present study was to determine if this assumption was robust, i.e. whether regression models derived from mean values accurately represented the distributions and boundaries of brain tissue volume at older ages.We acquired T1-w magnetic resonance (MR brain images of 227 normal and 219 Alzheimer's disease (AD subjects (aged 55-89 years from publicly available databanks. Using nonlinear regression within both samples, we compared mean and percentile rank estimates of whole brain tissue volume by age.In both the normal and AD sample, mean regression estimates of brain tissue volume often did not accurately represent percentile rank estimates (errors=-74% to 75%. In the normal sample, mean estimates generally underestimated differences in brain volume at percentile ranks below the mean. Conversely, in the AD sample, mean estimates generally underestimated differences in brain volume at percentile ranks above the mean. Differences between ages at the 5(th percentile rank of normal subjects were ~39% greater than mean differences in the AD subjects.While more data are required to make true population inferences, our results indicate that mean regression estimates may not accurately represent the distributions of ageing brain tissue volumes. This suggests that percentile rank estimates will be required to robustly define the limits of brain tissue volume in normal ageing and neurodegenerative disease.

  16. Defining and Measuring Entrepreneurship for Regional Research: A New Approach

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    Low, Sarah A.

    2009-01-01

    In this dissertation, I develop a definition and regional measure of entrepreneurship that will aid entrepreneurship research and economic development policy. My new indicators represent an improvement over current measures of entrepreneurship. The chief contribution of these new indicators is that they incorporate innovation, which others ignore.…

  17. Regional adaptation defines sensitivity to future ocean acidification

    Science.gov (United States)

    Calosi, Piero; Melatunan, Sedercor; Turner, Lucy M.; Artioli, Yuri; Davidson, Robert L.; Byrne, Jonathan J.; Viant, Mark R.; Widdicombe, Stephen; Rundle, Simon D.

    2017-01-01

    Physiological responses to temperature are known to be a major determinant of species distributions and can dictate the sensitivity of populations to global warming. In contrast, little is known about how other major global change drivers, such as ocean acidification (OA), will shape species distributions in the future. Here, by integrating population genetics with experimental data for growth and mineralization, physiology and metabolomics, we demonstrate that the sensitivity of populations of the gastropod Littorina littorea to future OA is shaped by regional adaptation. Individuals from populations towards the edges of the natural latitudinal range in the Northeast Atlantic exhibit greater shell dissolution and the inability to upregulate their metabolism when exposed to low pH, thus appearing most sensitive to low seawater pH. Our results suggest that future levels of OA could mediate temperature-driven shifts in species distributions, thereby influencing future biogeography and the functioning of marine ecosystems. PMID:28067268

  18. Using a panel of immunomarkers to define homologies in Mammalian brains.

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    Watson, Charles R; Paxinos, George; Tokuno, Hironobu

    2010-01-01

    Brain mapping has relied on a small number of routine chemical stains for many decades. The advent of immunomarkers has had a major impact on the ability to define homologous nuclei from one species to another. The first atlas to present a panel of immunomarkers was that of Paxinos et al. (1999a,b) in the adult rat brain. The markers used were parvalbumin, calbindin, calretinin, SMI32, tyrosine hydroxylase, and NADPH diaphorase (plus nissl and acetylcholinesterase). The 'signature' of a nucleus of interest in a new species can be tested against the findings in the rat. Since the pattern of immunomarkers seems to be conserved in mammalian evolution, such extrapolations can be made with reasonable confidence. A marmoset brain stained with a comprehensive set of immunomarkers has recently been published on the internet (Tokuno et al., 2009) and we are in the process of defining nuclear homologies in this brain by comparison with the same markers in the rat. In this article, we present an example (mapping the amygdala in the marmoset) which demonstrates the application of this immunomarker panel in defining homologies. The technique is particularly valuable in situations where little data on hodology or electrophysiology are available.

  19. Using a panel of immunomarkers to define homologies in mammalian brains

    Directory of Open Access Journals (Sweden)

    Charles R Watson

    2010-02-01

    Full Text Available Brain mapping has relied on a small number of routine chemical stains for many decades. The advent of immunomarkers has had a major impact on the ability to define homologous nuclei from one species to another. The first atlas to present a panel of immunomarkers was that of Paxinos et al. (1999a,b in the adult rat brain. The markers used were parvalbumin, calbindin, calretinin, SMI32, tyrosine hydroxylase, and NADPH diaphorase (plus nissl and acetylcholinesterase. The ‘signature’ of a nucleus of interest in a new species can be tested against the findings in the rat. Since the pattern of immunomarkers seems to be conserved in mammalian evolution, such extrapolations can be made with reasonable confidence. A marmoset brain stained with a comprehensive set of immunomarkers has recently been published on the internet (Tokuno et al 2009 and we are in the process of defining nuclear homologies in this brain by comparison with the same markers in the rat. In this article, we present an example (mapping the amygdala in the marmoset which demonstrates the application of this immunomarker panel in defining homologies. The technique is particularly valuable in situations where little data on hodology or electrophysiology are available.

  20. Automated regional behavioral analysis for human brain images

    National Research Council Canada - National Science Library

    Lancaster, Jack L; Laird, Angela R; Eickhoff, Simon B; Martinez, Michael J; Fox, P Mickle; Fox, Peter T

    2012-01-01

    Behavioral categories of functional imaging experiments along with standardized brain coordinates of associated activations were used to develop a method to automate regional behavioral analysis of human brain images...

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

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    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.

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

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

    2004-03-01

    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-[18F]fluoro-L-DOPA and one subject injected with [11C]CO-labelled red blood cells. In the phantom study, the diameter of syringes filled with an 11C 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.

  3. Lidar monitoring of regions of intense backscatter with poorly defined boundaries

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    Vladimir A. Kovalev; Alexander Petkov; Cyle Wold; WeiMin Hao

    2011-01-01

    The upper height of a region of intense backscatter with a poorly defined boundary between this region and a region of clear air above it is found as the maximal height where aerosol heterogeneity is detectable, that is, where it can be discriminated from noise. The theoretical basis behind the retrieval technique and the corresponding lidar-data-processing procedures...

  4. Anger Style, Psychopathology, and Regional Brain Activity

    OpenAIRE

    Stewart, Jennifer L.; Levin, Rebecca L.; Sass, Sarah M.; Heller, Wendy; Gregory A. Miller

    2008-01-01

    Depression and anxiety often involve high levels of trait anger and disturbances in anger expression. Reported anger experience and outward anger expression have recently been associated with left-biased asymmetry of frontal cortical activity, assumed to reflect approach motivation. However, different styles of anger expression could presumably involve different brain mechanisms and/or interact with psychopathology to produce various patterns of brain asymmetry. The present study explored the...

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

    Energy Technology Data Exchange (ETDEWEB)

    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.).

  6. Attenuation of Sindbis virus neurovirulence by using defined mutations in nontranslated regions of the genome RNA

    NARCIS (Netherlands)

    Kuhn, R J; Griffin, D E; Zhang, H; Niesters, Hubert G. M.; Strauss, J H

    1992-01-01

    We examined a panel of Sindbis virus mutants containing defined mutations in the 5' nontranslated region of the genome RNA, in the 3' nontranslated region, or in both for their growth in cultured cells and virulence in newborn mice. In cultured cells, these viruses all had defects in RNA synthesis a

  7. Decoding Brain States Based on Magnetoencephalography From Prespecified Cortical Regions.

    Science.gov (United States)

    Zhang, Jinyin; Li, Xin; Foldes, Stephen T; Wang, Wei; Collinger, Jennifer L; Weber, Douglas J; Bagić, Anto

    2016-01-01

    Brain state decoding based on whole-head MEG has been extensively studied over the past decade. Recent MEG applications pose an emerging need of decoding brain states based on MEG signals originating from prespecified cortical regions. Toward this goal, we propose a novel region-of-interest-constrained discriminant analysis algorithm (RDA) in this paper. RDA integrates linear classification and beamspace transformation into a unified framework by formulating a constrained optimization problem. Our experimental results based on human subjects demonstrate that RDA can efficiently extract the discriminant pattern from prespecified cortical regions to accurately distinguish different brain states.

  8. Defining acute ischemic stroke tissue pathophysiology with whole brain CT perfusion.

    Science.gov (United States)

    Bivard, A; Levi, C; Krishnamurthy, V; Hislop-Jambrich, J; Salazar, P; Jackson, B; Davis, S; Parsons, M

    2014-12-01

    This study aimed to identify and validate whole brain perfusion computed tomography (CTP) thresholds for ischemic core and salvageable penumbra in acute stroke patients and develop a probability based model to increase the accuracy of tissue pathophysiology measurements. One hundred and eighty-three patients underwent multimodal stroke CT using a 320-slice scanner within 6hours of acute stroke onset, followed by 24hour MRI that included diffusion weighted imaging (DWI) and dynamic susceptibility weighted perfusion imaging (PWI). Coregistered acute CTP and 24hour DWI was used to identify the optimum single perfusion parameter thresholds to define penumbra (in patients without reperfusion), and ischemic core (in patients with reperfusion), using a pixel based receiver operator curve analysis. Then, these results were used to develop a sigma curve fitted probability based model incorporating multiple perfusion parameter thresholds. For single perfusion thresholds, a time to peak (TTP) of +5seconds best defined the penumbra (area under the curve, AUC 0.79 CI 0.74-0.83) while a cerebral blood flow (CBF) of acute ischemic core (AUC 0.73, CI 0.69-0.77). The probability model was more accurate at detecting the ischemic core (AUC 0.80 SD 0.75-0.83) and penumbra (0.85 SD 0.83-0.87) and was significantly closer in volume to the corresponding reference DWI (P=0.031). Whole brain CTP can accurately identify penumbra and ischemic core using similar thresholds to previously validated 16 or 64 slice CTP. Additionally, a novel probability based model was closer to defining the ischemic core and penumbra than single thresholds. Copyright © 2013 Elsevier Masson SAS. All rights reserved.

  9. On Expression Patterns and Developmental Origin of Human Brain Regions.

    Science.gov (United States)

    Kirsch, Lior; Chechik, Gal

    2016-08-01

    Anatomical substructures of the human brain have characteristic cell-types, connectivity and local circuitry, which are reflected in area-specific transcriptome signatures, but the principles governing area-specific transcription and their relation to brain development are still being studied. In adult rodents, areal transcriptome patterns agree with the embryonic origin of brain regions, but the processes and genes that preserve an embryonic signature in regional expression profiles were not quantified. Furthermore, it is not clear how embryonic-origin signatures of adult-brain expression interplay with changes in expression patterns during development. Here we first quantify which genes have regional expression-patterns related to the developmental origin of brain regions, using genome-wide mRNA expression from post-mortem adult human brains. We find that almost all human genes (92%) exhibit an expression pattern that agrees with developmental brain-region ontology, but that this agreement changes at multiple phases during development. Agreement is particularly strong in neuron-specific genes, but also in genes that are not spatially correlated with neuron-specific or glia-specific markers. Surprisingly, agreement is also stronger in early-evolved genes. We further find that pairs of similar genes having high agreement to developmental region ontology tend to be more strongly correlated or anti-correlated, and that the strength of spatial correlation changes more strongly in gene pairs with stronger embryonic signatures. These results suggest that transcription regulation of most genes in the adult human brain is spatially tuned in a way that changes through life, but in agreement with development-determined brain regions.

  10. Indices of Regional Brain Atrophy: Formulae and Nomenclature

    Science.gov (United States)

    Arias-Carrión, Oscar

    2015-01-01

    The pattern of brain atrophy helps to discriminate normal age-related changes from neurodegenerative diseases. Albeit indices of regional brain atrophy have proven to be a parameter useful in the early diagnosis and differential diagnosis of some neurodegenerative diseases, indices of absolute regional atrophy still have some important limitations. We propose using indices of relative atrophy for representing how the volume of a given region of interest (ROI) changes over time in comparison to changes in global brain measures over the same time. A second problem in morphometric studies is terminology. There is a lack of systematization naming indices and the same measure can be named with different terms by different research groups or imaging softwares. This limits the understanding and discussion of studies. In this technological report, we provide a general description on how to compute indices of absolute and relative regional brain atrophy and propose a standardized nomenclature. PMID:26261753

  11. Morphogenesis and regionalization of the medaka embryonic brain.

    Science.gov (United States)

    Kage, Takahiro; Takeda, Hiroyuki; Yasuda, Takako; Maruyama, Kouichi; Yamamoto, Naoyuki; Yoshimoto, Masami; Araki, Kazuo; Inohaya, Keiji; Okamoto, Hiroyuki; Yasumasu, Shigeki; Watanabe, Kaori; Ito, Hironobu; Ishikawa, Yuji

    2004-08-23

    We examined the morphogenesis and regionalization of the embryonic brain of an acanthopterygian teleost, medaka (Oryzias latipes), by in situ hybridization using 14 gene probes. We compared our results with previous studies in other vertebrates, particularly zebrafish, an ostariophysan teleost. During the early development of the medaka neural rod, three initial brain vesicles arose: the anterior brain vesicle, which later developed into the telencephalon and rostral diencephalon; the intermediate brain vesicle, which later developed into the caudal diencephalon, mesencephalon, and metencephalon; and the posterior brain vesicle, which later developed into the myelencephalon. In the late neural rod, the rostral brain bent ventrally and the axis of the brain had a marked curvature at the diencephalon. In the final stage of the neural rod, ventricles began to develop, transforming the neural rod into the neural tube. In situ hybridization revealed that the brain can be divided into three longitudinal zones (dorsal, intermediate, and ventral) and many transverse subdivisions, on the basis of molecular expression patterns. The telencephalon was subdivided into two transverse domains. Our results support the basic concept of neuromeric models, including the prosomeric model, which suggests the existence of a conserved organization of all vertebrate neural tubes. Our results also show that brain development in medaka differs from that reported in other vertebrates, including zebrafish, in gene-expression patterns in the telencephalon, in brain vesicle formation, and in developmental speed. Developmental and genetic programs for brain development may be somewhat different even among teleosts.

  12. Resolving brain regions using nanostructure initiator mass spectrometry imaging

    OpenAIRE

    Lee, Do Yup; Platt, Virginia; Bowen, Ben; Louie, Katherine; Canaria, Christie; McMurray, Cynthia T.; Northen, Trent

    2012-01-01

    Specific cell types are critically implicated in a variety of neuropathologies that exhibit region-specific susceptibility. Neuronal and glial function is impaired in a host of neurodegenerative diseases. Previous reports suggest that mass spectrometry imaging has the potential to resolve cell-specific enrichment in brain regions; however, individual ions cannot resolve glial and neuronal cells within the complex structure of brain tissue. Here, we utilized a matrix-free surface mass spectrom...

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

    Science.gov (United States)

    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

  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. 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/.

  16. 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.

  17. Defining the critical hypoxic threshold that promotes vascular remodeling in the brain.

    Science.gov (United States)

    Boroujerdi, Amin; Milner, Richard

    2015-01-01

    In animal models, hypoxic pre-conditioning confers protection against subsequent neurological insults, mediated in part through an extensive vascular remodeling response. In light of the therapeutic potential of this effect, the goal of this study was to establish the dose-response relationship between level of hypoxia and the extent of cerebrovascular modeling, and to define the mildest level of hypoxia that promotes remodeling. Mice were exposed to different levels of continuous hypoxia (8-21% O2) for seven days before several aspects of vascular remodeling were evaluated, including endothelial proliferation, total vascular area, arteriogenesis, and fibronectin/α5β1 integrin expression. For most events, the threshold level of hypoxia that stimulated remodeling was 12-13% O2. Interestingly, many parameters displayed a biphasic dose-response curve, with peak levels attained at 10% O2, but declined thereafter. Further analysis in the 12-13% O2 range revealed that vascular remodeling occurs by two separate mechanisms: (i) endothelial hyperplasia, triggered by a hypoxic threshold of 13% O2, which leads to increased capillary growth, and (ii) endothelial hypertrophy, triggered by a more severe hypoxic threshold of 12% O2, which leads to expansion of large vessels and arteriogenesis. Taken together, these results define the hypoxic thresholds for vascular remodeling in the brain, and point to two separate mechanisms mediating this process.

  18. 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

  19. 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... Semen § 98.38 Restrictions on the importation of swine semen from the APHIS-defined EU CSF region. In...-defined EU CSF region must meet the following conditions, except as noted in paragraph (h) of this...

  20. A new methodology to define homogeneous regions through an entropy based clustering method

    Science.gov (United States)

    Ridolfi, E.; Rianna, M.; Trani, G.; Alfonso, L.; Di Baldassarre, G.; Napolitano, F.; Russo, F.

    2016-10-01

    One of the most crucial steps in flow frequency studies is the definition of Homogenous Regions (HRs), i.e. areas with similar hydrological behavior. This is essential in ungauged catchments, as HR allows information to be transferred from a neighboring river basin. This study proposes a new, entropy-based approach to define HRs, in which regions are defined as homogeneous if their hydrometric stations capture redundant information. The problem is handled through the definition of the Information Transferred Index (ITI) as the ratio between redundant information and the total information provided by pairs of stations. The methodology is compared with a traditional, distance-based clustering method through a Monte Carlo experiment and a jack-knife procedure. Results indicate that the ITI-based method performs well, adding value to current methodologies to define HRs.

  1. 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

  2. Genetically and functionally defined NTS to PBN brain circuits mediating anorexia.

    Science.gov (United States)

    Roman, Carolyn W; Derkach, Victor A; Palmiter, Richard D

    2016-06-15

    The central nervous system controls food consumption to maintain metabolic homoeostasis. In response to a meal, visceral signals from the gut activate neurons in the nucleus of the solitary tract (NTS) via the vagus nerve. These NTS neurons then excite brain regions known to mediate feeding behaviour, such as the lateral parabrachial nucleus (PBN). We previously described a neural circuit for appetite suppression involving calcitonin gene-related protein (CGRP)-expressing PBN (CGRP(PBN)) neurons; however, the molecular identity of the inputs to these neurons was not established. Here we identify cholecystokinin (CCK) and noradrenergic, dopamine β-hydroxylase (DBH)-expressing NTS neurons as two separate populations that directly excite CGRP(PBN) neurons. When these NTS neurons are activated using optogenetic or chemogenetic methods, food intake decreases and with chronic stimulation mice lose body weight. Our optogenetic results reveal that CCK and DBH neurons in the NTS directly engage CGRP(PBN) neurons to promote anorexia.

  3. Genetically and functionally defined NTS to PBN brain circuits mediating anorexia

    Science.gov (United States)

    Roman, Carolyn W.; Derkach, Victor A.; Palmiter, Richard D.

    2016-01-01

    The central nervous system controls food consumption to maintain metabolic homoeostasis. In response to a meal, visceral signals from the gut activate neurons in the nucleus of the solitary tract (NTS) via the vagus nerve. These NTS neurons then excite brain regions known to mediate feeding behaviour, such as the lateral parabrachial nucleus (PBN). We previously described a neural circuit for appetite suppression involving calcitonin gene-related protein (CGRP)-expressing PBN (CGRPPBN) neurons; however, the molecular identity of the inputs to these neurons was not established. Here we identify cholecystokinin (CCK) and noradrenergic, dopamine β-hydroxylase (DBH)-expressing NTS neurons as two separate populations that directly excite CGRPPBN neurons. When these NTS neurons are activated using optogenetic or chemogenetic methods, food intake decreases and with chronic stimulation mice lose body weight. Our optogenetic results reveal that CCK and DBH neurons in the NTS directly engage CGRPPBN neurons to promote anorexia. PMID:27301688

  4. Regional manifold learning for deformable registration of brain MR images.

    Science.gov (United States)

    Ye, Dong Hye; Hamm, Jihun; Kwon, Dongjin; Davatzikos, Christos; Pohl, Kilian M

    2012-01-01

    We propose a method for deformable registration based on learning the manifolds of individual brain regions. Recent publications on registration of medical images advocate the use of manifold learning in order to confine the search space to anatomically plausible deformations. Existing methods construct manifolds based on a single metric over the entire image domain thus frequently miss regional brain variations. We address this issue by first learning manifolds for specific regions and then computing region-specific deformations from these manifolds. We then determine deformations for the entire image domain by learning the global manifold in such a way that it preserves the region-specific deformations. We evaluate the accuracy of our method by applying it to the LPBA40 dataset and measuring the overlap of the deformed segmentations. The result shows significant improvement in registration accuracy on cortex regions compared to other state of the art methods.

  5. Brain regionalization: of signaling centers and boundaries.

    Science.gov (United States)

    Cavodeassi, Florencia; Houart, Corinne

    2012-03-01

    Our knowledge of the general mechanisms controlling the formation of the vertebrate central nervous system has advanced tremendously in the last decade. Here, we discuss the impact of the combined use of cell manipulation, in vivo imaging and genetics in the zebrafish on recent progress in understanding how signaling processes progressively control regionalization of the central nervous system. We highlight the unresolved issues and speculate upon the fundamental role the zebrafish will continue having in answering them.

  6. 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 < 0.1cm-1). Image analysis was performed on the attenuation coefficient images to derive quantitative endpoints. We observed a statistically significant difference among the median attenuation coefficients of these five regions (one-way ANOVA, p<0.05). 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.

  7. Differential transcription in defined parts of the insect brain: comparative study utilizing Drosophila melanogaster and Schistocerca gregaria.

    Science.gov (United States)

    Roeder, Thomas; Schramm, Guido; Marquardt, Helge; Bussmeyer, Ingo; Franz, Oliver

    2004-10-01

    The brain of all higher organisms has a modular architecture. Processing of various tasks, such as learning, olfaction, or motor control is performed in specialized brain areas, characterized by morphological and molecular peculiarities. To identify those genes that are transcribed in only one region of the insect brain, we chose two different approaches, differential display PCR and DNA array hybridization, with two different insect species, the desert locust Schistocerca gregaria and the fruitfly Drosophila melanogaster. The optic lobes (centers of visual information processing), the midbrain (the region of the brain where almost all "higher" centers are localized), and the thoracic ganglia (regions required to control various peripheral organs) were compared in both types of experiments. Both, the differential display PCR screen of the different parts of the locust brain as well as the DNA array screen of the Drosophila brain revealed almost identical numbers of transcripts exclusively present in either of the three above-mentioned brain areas. Interestingly, the brain areas with the largest number of differential transcripts are the thoracic ganglia and not the midbrain.

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

    Science.gov (United States)

    Strangman, Gary E; O'Neil-Pirozzi, Therese M; Supelana, Christina; Goldstein, Richard; Katz, Douglas I; Glenn, Mel B

    2010-01-01

    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 1-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.

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

    Directory of Open Access Journals (Sweden)

    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.

  10. STUDY OF REGIONAL STABILITY OF ECD DISTRIBUTION IN NORMAL BRAIN

    Institute of Scientific and Technical Information of China (English)

    李培勇; 陈刚; 朱承谟

    2001-01-01

    Objective To evaluate in vivo stability of ethylenedylbis cysteine diethylester ( ECD ) brain SPECT. Methods Each of13 normal volunteers (31.2±11.8 years) has12 dynamic SPECT scans acquired in 60min 1h after an injection of 99mTc-ECD using a triple headed gamma camera equipped with ultra high resolution fan beam collimators. Average counts per pixel were measured from frontal, temporal, parietal, occipital regions, cerebellum, basal ganglia, thalamus and white matter. Regional ECD clearance rates, regional gray-to-white matter (G/W) ratios and the change of the G /W ratio were calculated. Results The average ECD clearance rate was 4.2%/h, ranged from 3.03%/h to 5.41%/h corresponding to white matter and occipital. There was no significant difference between regional ECD clearance rates. Regional G/W ratio was between 1.27 to 1.75. The G /W ratio of temporal lobe was lower than the occipital (P<0.05). The change of regional G /W ratio with time is slow. Cbnclusion Regional ECD distribution is stable in normal brain. ECD clearance from brain is slow and no significant regional difference.

  11. Specific regions of the brain are capable of fructose metabolism.

    Science.gov (United States)

    Oppelt, Sarah A; Zhang, Wanming; Tolan, Dean R

    2017-02-15

    High fructose consumption in the Western diet correlates with disease states such as obesity and metabolic syndrome complications, including type II diabetes, chronic kidney disease, and non-alcoholic fatty acid liver disease. Liver and kidneys are responsible for metabolism of 40-60% of ingested fructose, while the physiological fate of the remaining fructose remains poorly understood. The primary metabolic pathway for fructose includes the fructose-transporting solute-like carrier transport proteins 2a (SLC2a or GLUT), including GLUT5 and GLUT9, ketohexokinase (KHK), and aldolase. Bioinformatic analysis of gene expression encoding these proteins (glut5, glut9, khk, and aldoC, respectively) identifies other organs capable of this fructose metabolism. This analysis predicts brain, lymphoreticular tissue, placenta, and reproductive tissues as possible additional organs for fructose metabolism. While expression of these genes is highest in liver, the brain is predicted to have expression levels of these genes similar to kidney. RNA in situ hybridization of coronal slices of adult mouse brains validate the in silico expression of glut5, glut9, khk, and aldoC, and show expression across many regions of the brain, with the most notable expression in the cerebellum, hippocampus, cortex, and olfactory bulb. Dissected samples of these brain regions show KHK and aldolase enzyme activity 5-10 times the concentration of that in liver. Furthermore, rates of fructose oxidation in these brain regions are 15-150 times that of liver slices, confirming the bioinformatics prediction and in situ hybridization data. This suggests that previously unappreciated regions across the brain can use fructose, in addition to glucose, for energy production. Copyright © 2016 Elsevier B.V. All rights reserved.

  12. Reproducibility of regional brain metabolic responses to lorazepam

    Energy Technology Data Exchange (ETDEWEB)

    Wang, G.J.; Volkow, N.D.; Overall, J. [Brookhaven National Lab., Upton, NY (United States)]|[SUNY, Stony Brook, NY (United States)] [and others

    1996-10-01

    Changes in regional brain glucose metabolism in response to benzodiazepine agonists have been used as indicators of benzodiazepine-GABA receptor function. The purpose of this study was to assess the reproducibility of these responses. Sixteen healthy right-handed men underwent scanning with PET and [{sup 18}F]fluorodeoxyglucose (FDG) twice: before placebo and before lorazepam (30 {mu}g/kg). The same double FDG procedure was repeated 6-8 wk later on the men to assess test-retest reproducibility. The regional absolute brain metabolic values obtained during the second evaluation were significantly lower than those obtained from the first evaluation regardless of condition (p {le} 0.001). Lorazepam significantly and consistently decreased both whole-brain metabolism and the magnitude. The regional pattern of the changes were comparable for both studies (12.3% {plus_minus} 6.9% and 13.7% {plus_minus} 7.4%). Lorazepam effects were the largest in the thalamus (22.2% {plus_minus} 8.6% and 22.4% {plus_minus} 6.9%) and occipital cortex (19% {plus_minus} 8.9% and 21.8% {plus_minus} 8.9%). Relative metabolic measures were highly reproducible both for pharmacolgic and replication condition. This study measured the test-retest reproducibility in regional brain metabolic responses, and although the global and regional metabolic values were significantly lower for the repeated evaluation, the response to lorazepam was highly reproducible. 1613 refs., 3 figs., 3 tabs.

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

    Science.gov (United States)

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

    2012-02-01

    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.

  14. 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.

  15. Random Forest Segregation of Drug Responses May Define Regions of Biological Significance.

    Science.gov (United States)

    Bukhari, Qasim; Borsook, David; Rudin, Markus; Becerra, Lino

    2016-01-01

    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 a supervised 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.

  16. 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 meta

  17. 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 meta

  18. 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.…

  19. 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.…

  20. Cytopathological evaluations combined RNA and protein analyses on defined cell regions using single frozen tissue block.

    Science.gov (United States)

    Li, Hong; Chen, Xiao Yan; Kong, Qing You; Liu, Jia

    2002-06-01

    The co-existence of multiple cell components in tissue samples is the main obstacle for precise molecular evaluation on defined cell types. Based on morphological examination, we developed an efficient approach for paralleled RNA and protein isolations from an identical histological region in frozen tissue section. The RNA and protein samples prepared were sufficient for RT-PCR and Western blot analyses, and the results obtained were well coincident each other as well as with the corresponding parameters revealed from immunohistochemical examinations. By this way, the sampling problem caused by cell-cross contamination can be largely avoided, committing the experimental data more specific to a defined cell type. These novel methods thus allow us to use single tissue block for a comprehensive study by integration of conventional cytological evaluations with nucleic acid and protein analyses.

  1. Cytopathological evaluations combined RNA and protein analyses on defined cell regions using single frozen tissue block

    Institute of Scientific and Technical Information of China (English)

    2002-01-01

    The co-existence of multiple cell components in tissue samples is the main obstacle for precise molecular evaluation on defined cell types. Based on morphological examination, we developed an efficient approach for paralleled RNA and protein isolations from an identical histological region in frozen tissue section.The RNA and protein samples prepared were sufficient for RT-PCR and Western blot analyses, and the results obtained were well coincident each other as well as with the corresponding parameters revealed from immunohistochemical examinations. By this way, the sampling problem caused by cell-cross contamination can be largely avoided, committing the experimental data more specific to a defined cell type. These novel methods thus allow us to use single tissue block for a comprehensive study by integration of conventional cytological evaluations with nucleic acid and protein analyses.

  2. Regional brain stiffness changes across the Alzheimer's disease spectrum.

    Science.gov (United States)

    Murphy, Matthew C; Jones, David T; Jack, Clifford R; Glaser, Kevin J; Senjem, Matthew L; Manduca, Armando; Felmlee, Joel P; Carter, Rickey E; Ehman, Richard L; Huston, John

    2016-01-01

    Magnetic resonance elastography (MRE) is an MRI-based technique to noninvasively measure tissue stiffness. Currently well established for clinical use in the liver, MRE is increasingly being investigated to measure brain stiffness as a novel biomarker of a variety of neurological diseases. The purpose of this work was to apply a recently developed MRE pipeline to measure regional brain stiffness changes in human subjects across the Alzheimer's disease (AD) spectrum, and to gain insights into the biological processes underlying those stiffness changes by correlating stiffness with existing biomarkers of AD. The results indicate that stiffness changes occur mostly in the frontal, parietal and temporal lobes, in accordance with the known topography of AD pathology. Furthermore, stiffness in those areas correlates with existing imaging biomarkers of AD including hippocampal volumes and amyloid PET. Additional analysis revealed preliminary but significant evidence that the relationship between brain stiffness and AD severity is nonlinear and non-monotonic. Given that similar relationships have been observed in functional MRI experiments, we used task-free fMRI data to test the hypothesis that brain stiffness was sensitive to structural changes associated with altered functional connectivity. The analysis revealed that brain stiffness is significantly and positively correlated with default mode network connectivity. Therefore, brain stiffness as measured by MRE has potential to provide new and essential insights into the temporal dynamics of AD, as well as the relationship between functional and structural plasticity as it relates to AD pathophysiology.

  3. Regional brain axial and radial diffusivity changes during development.

    Science.gov (United States)

    Kumar, Rajesh; Nguyen, Haidang D; Macey, Paul M; Woo, Mary A; Harper, Ronald M

    2012-02-01

    The developing human brain shows rapid myelination and axonal changes during childhood, adolescence, and early adulthood, requiring successive evaluations to determine normative values for potential pathological assessment. Fiber characteristics can be examined by axial and radial diffusivity procedures, which measure water diffusion parallel and perpendicular to axons and show primarily axonal status and myelin changes, respectively. Such measures are lacking from widespread sites for the developing brain. Diffusion tensor imaging data were acquired from 30 healthy subjects (age 17.7 ± 4.6 years, range 8-24 years, body mass index 21.5 ± 4.5 kg/m(2), 18 males) using a 3.0-Tesla MRI scanner. Diffusion tensors were calculated, principal eigenvalues determined, and axial and radial diffusivity maps calculated and normalized to a common space. A set of regions of interest was outlined from widespread brain areas within rostral, thalamic, hypothalamic, cerebellar, and pontine regions, and average diffusivity values were calculated using normalized diffusivity maps and these regions of interest masks. Age-related changes were assessed with Pearson's correlations, and gender differences evaluated with Student's t-tests. Axial and radial diffusivity values declined with age in the majority of brain areas, except for midhippocampus, where axial diffusivity values correlated positively with age. Gender differences emerged within putamen, thalamic, hypothalamic, cerebellar, limbic, temporal, and other cortical sites. Documentation of normal axial and radial diffusivity values will help assess disease-related tissue changes. Axial and radial diffusivities change with age,with fiber structure and organization differing between sexes in several brain areas. The findings may underlie gender-based functional characteristics, and mandate partitioning age- and gender-related changes during developmental brain pathology evaluation.

  4. Thyroid hormone receptors bind to defined regions of the growth hormone and placental lactogen genes.

    Science.gov (United States)

    Barlow, J W; Voz, M L; Eliard, P H; Mathy-Harter, M; De Nayer, P; Economidis, I V; Belayew, A; Martial, J A; Rousseau, G G

    1986-12-01

    The intracellular receptor for thyroid hormone is a protein found in chromatin. Since thyroid hormone stimulates transcription of the growth hormone gene through an unknown mechanism, the hypothesis that the thyroid hormone-receptor complex interacts with defined regions of this gene has been investigated in a cell-free system. Nuclear extracts from human lymphoblastoid IM-9 cells containing thyroid hormone receptors were incubated with L-3,5,3'-tri[125I]iodothyronine and calf thymus DNA-cellulose. Restriction fragments of the human growth hormone gene were added to determine their ability to inhibit labeled receptor binding to DNA-cellulose. These fragments encompassed nucleotide sequences from about three kilobase pairs upstream to about four kilobase pairs downstream from the transcription initiation site. The thyroid hormone-receptor complex bound preferentially to the 5'-flanking sequences of the growth hormone gene in a region between nucleotide coordinates -290 and -129. The receptor also bound to an analogous promoter region in the human placental lactogen gene, which has 92% nucleotide sequence homology with the growth hormone gene. These binding regions appear to be distinct from those that are recognized by the receptor for glucocorticoids, which stimulate growth hormone gene expression synergistically with thyroid hormone. The presence of thyroid hormone was required for binding of its receptor to the growth hormone gene promoter, suggesting that thyroid hormone renders the receptor capable of recognizing specific gene regions.

  5. The transitional association between β-amyloid pathology and regional brain atrophy.

    Science.gov (United States)

    Insel, Philip S; Mattsson, Niklas; Donohue, Michael C; Mackin, R Scott; Aisen, Paul S; Jack, Clifford R; Shaw, Leslie M; Trojanowski, John Q; Weiner, Michael W

    2015-10-01

    Alzheimer's disease (AD) is characterized by the accumulation of β-amyloid (Aβ) associated with brain atrophy and cognitive decline. The functional form to model the association between Aβ and regional brain atrophy has not been well defined. To determine the relationship between Aβ and atrophy, we compared the performance of the usual dichotomization of cerebrospinal fluid (CSF) Aβ to identify subjects as Aβ+ and Aβ- with a trilinear spline model of CSF Aβ. One hundred and eighty-three subjects with mild cognitive impairment and 108 cognitively normal controls with baseline CSF Aβ and up to 4 years of longitudinal magnetic resonance imaging data from the Alzheimer's Disease Neuroimaging Initiative were analyzed using mixed-effects regression. Piecewise-linear splines were used to evaluate the nonlinear nature of the association between CSF Aβ and regional atrophy and to identify points of acceleration of atrophy with respect to Aβ. Several parameterizations of CSF Aβ were compared using likelihood ratio tests and the Akaike information criterion. Periods of acceleration of atrophy in which subjects transition from CSF Aβ negativity to CSF Aβ positivity were estimated from the spline models and tested for significance. Spline models resulted in better fits for many temporal and parietal regions compared with the dichotomous models. The trilinear model showed that periods of acceleration of atrophy varied greatly by region with early changes seen in the insula, amygdala, precuneus, hippocampus, and other temporal regions, occurring before the clinical threshold for CSF Aβ positivity. The use of piecewise-linear splines provides an improved model of the nonlinear association between CSF Aβ and regional atrophy in regions implicated in the progression of AD. The important biological finding of this work is that some brain regions show periods of accelerated volume loss well before the CSF Aβ42 threshold. This implies that signs of brain atrophy

  6. Distribution of Non-Persistent Endocrine Disruptors in Two Different Regions of the Human Brain.

    Science.gov (United States)

    van der Meer, Thomas P; Artacho-Cordón, Francisco; Swaab, Dick F; Struik, Dicky; Makris, Konstantinos C; Wolffenbuttel, Bruce H R; Frederiksen, Hanne; van Vliet-Ostaptchouk, Jana V

    2017-09-13

    Non-persistent endocrine disrupting chemicals (npEDCs) can affect multiple organs and systems in the body. Whether npEDCs can accumulate in the human brain is largely unknown. The major aim of this pilot study was to examine the presence of environmental phenols and parabens in two distinct brain regions: the hypothalamus and white-matter tissue. In addition, a potential association between these npEDCs concentrations and obesity was investigated. Post-mortem brain material was obtained from 24 individuals, made up of 12 obese and 12 normal-weight subjects (defined as body mass index (BMI) > 30 and BMI < 25 kg/m², respectively). Nine phenols and seven parabens were measured by isotope dilution TurboFlow-LC-MS/MS. In the hypothalamus, seven suspect npEDCs (bisphenol A, triclosan, triclocarban and methyl-, ethyl-, n-propyl-, and benzyl paraben) were detected, while five npEDCs (bisphenol A, benzophenone-3, triclocarban, methyl-, and n-propyl paraben) were found in the white-matter brain tissue. We observed higher levels of methylparaben (MeP) in the hypothalamic tissue of obese subjects as compared to controls (p = 0.008). Our findings indicate that some suspected npEDCs are able to cross the blood-brain barrier. Whether the presence of npEDCs can adversely affect brain function and to which extent the detected concentrations are physiologically relevant needs to be further investigated.

  7. 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...

  8. Sex differences in brain structure in auditory and cingulate regions

    OpenAIRE

    Brun, Caroline C.; Lepore, Natasha; Luders, Eileen; Chou, Yi-Yu; Madsen, Sarah K.; Toga, Arthur W; Thompson, Paul M.

    2009-01-01

    We applied a new method to visualize the three-dimensional profile of sex differences in brain structure based on MRI scans of 100 young adults. We compared 50 men with 50 women, matched for age and other relevant demographics. As predicted, left hemisphere auditory and language-related regions were proportionally expanded in women versus men, suggesting a possible structural basis for the widely replicated sex differences in language processing. In men, primary visual, and visuo-spatial asso...

  9. Aerobic exercise reduces neuronal responses in food reward brain regions.

    Science.gov (United States)

    Evero, Nero; Hackett, Laura C; Clark, Robert D; Phelan, Suzanne; Hagobian, Todd A

    2012-05-01

    Acute exercise suppresses ad libitum energy intake, but little is known about the effects of exercise on food reward brain regions. After an overnight fast, 30 (17 men, 13 women), healthy, habitually active (age = 22.2 ± 0.7 yr, body mass index = 23.6 ± 0.4 kg/m(2), Vo(2peak) = 44.2 ± 1.5 ml·kg(-1)·min(-1)) individuals completed 60 min of exercise on a cycle ergometer or 60 min of rest (no-exercise) in a counterbalanced, crossover fashion. After each condition, blood oxygen level-dependent responses to high-energy food, low-energy food, and control visual cues, were measured by functional magnetic resonance imaging. Exercise, compared with no-exercise, significantly (P Exercise alone significantly (P exercise alone significantly (P Exercise reduced neuronal responses in brain regions consistent with reduced pleasure of food, reduced incentive motivation to eat, and reduced anticipation and consumption of food. Reduced neuronal response in these food reward brain regions after exercise is in line with the paradigm that acute exercise suppresses subsequent energy intake.

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

    OpenAIRE

    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 meta-analysis of genome-wide association studies of white participants in 6 studies comprising the Cohorts for Heart and Aging Research in Genomic Epidemiology (CHARGE) consortium. Methods-Using 2.2 mi...

  11. Regional mechanical properties of human brain tissue for computational models of traumatic brain injury.

    Science.gov (United States)

    Finan, John D; Sundaresh, Sowmya N; Elkin, Benjamin S; McKhann, Guy M; Morrison, Barclay

    2017-06-01

    To determine viscoelastic shear moduli, stress relaxation indentation tests were performed on samples of human brain tissue resected in the course of epilepsy surgery. Through the use of a 500µm diameter indenter, regional mechanical properties were measured in cortical grey and white matter and subregions of the hippocampus. All regions were highly viscoelastic. Cortical grey matter was significantly more compliant than the white matter or hippocampus which were similar in modulus. Although shear modulus was not correlated with the age of the donor, cortex from male donors was significantly stiffer than from female donors. The presented material properties will help to populate finite element models of the brain as they become more anatomically detailed. We present the first mechanical characterization of fresh, post-operative human brain tissue using an indentation loading mode. Indentation generates highly localized data, allowing structure-specific mechanical properties to be determined from small tissue samples resected during surgery. It also avoids pitfalls of cadaveric tissue and allows data to be collected before degenerative processes alter mechanical properties. To correctly predict traumatic brain injury, finite element models must calculate intracranial deformation during head impact. The functional consequences of injury depend on the anatomical structures injured. Therefore, morbidity depends on the distribution of deformation across structures. Accurate prediction of structure-specific deformation requires structure-specific mechanical properties. This data will facilitate deeper understanding of the physical mechanisms that lead to traumatic brain injury. Copyright © 2017 Acta Materialia Inc. Published by Elsevier Ltd. All rights reserved.

  12. A new region of conservation is defined between human and mouse X chromosomes

    Energy Technology Data Exchange (ETDEWEB)

    Dinulos, M.B.; Disteche, C.M. [Univ. of Washington, Seattle, WA (United States); Bassi, M.T. [Univ. of Siena (Italy)] [and others

    1996-07-01

    Comparative mapping of the X chromosome in eutherian mammals have revealed distinct regions of conservation as well as evolutionary rearrangements between human and mouse. Recently, we and others mapped the murine homologue of CLCN4 (Chloride channel 4) to band F4 of the X chromosome in Mus spretus but to chromosome 7 in laboratory strains. We now report the mapping of the murine homologues of APXL (Apical protein Xenopus laevis-like) and OA1 (Ocular albinism type I), two genes that are located on the human X chromosome at band p22.3 and in close proximity to CLCN4. Interestingly, Oa1 and Apxl map to bands F2-F3 in both M. spretus and the laboratory strain C57BL/6J, defining a new rearrangement between human and mouse X chromosomes. 17 refs., 2 figs., 1 tab.

  13. Genome-wide Association Studies of MRI-defined Brain Infarcts: Meta-analysis from the CHARGE Consortium

    Science.gov (United States)

    Debette, Stephanie; Bis, Joshua C.; Fornage, Myriam; Schmidt, Helena; Ikram, M. Arfan; Sigurdsson, Sigurdur; Heiss, Gerardo; Struchalin, Maksim; Smith, Albert V.; van der Lugt, Aad; DeCarli, Charles; Lumley, Thomas; Knopman, David S.; Enzinger, Christian; Eiriksdottir, Gudny; Koudstaal, Peter J.; DeStefano, Anita L.; Psaty, Bruce M.; Dufouil, Carole; Catellier, Diane J.; Fazekas, Franz; Aspelund, Thor; Aulchenko, Yurii S.; Beiser, Alexa; Rotter, Jerome I.; Tzourio, Christophe; Shibata, Dean K.; Tscherner, Maria; Harris, Tamara B.; Rivadeneira, Fernando; Atwood, Larry D.; Rice, Kenneth; Gottesman, Rebecca F.; van Buchem, Mark A.; Uitterlinden, Andre G.; Kelly-Hayes, Margaret; Cushman, Mary; Zhu, Yicheng; Boerwinkle, Eric; Gudnason, Vilmundur; Hofman, Albert; Romero, Jose R.; Lopez, Oscar; van Duijn, Cornelia M.; Au, Rhoda; Heckbert, Susan R.; Wolf, Philip A.; Mosley, Thomas H.; Seshadri, Sudha; Breteler, Monique M.B.; Schmidt, Reinhold; Launer, Lenore J.; Longstreth, WT

    2010-01-01

    Background 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 meta-analysis of genome-wide association studies of white participants in 6 studies comprising the Cohorts for Heart and Aging Research in Genomic Epidemiology (CHARGE) consortium. Methods Using 2.2 million genotyped and imputed SNPs, each study performed cross-sectional genome-wide association analysis of MRI-infarct using age and sex-adjusted logistic regression models. Study-specific findings were combined in an inverse-variance weighted meta-analysis, including 9401 participants with mean age 69.7, 19.4% of whom had ≥1 MRI-infarct. Results The most significant association was found with rs2208454 (minor allele frequency: 20%), located in intron 3 of MACRO Domain Containing 2 gene and in the downstream region of Fibronectin Leucine Rich Transmembrane Protein 3 gene. Each copy of the minor allele was associated with lower risk of MRI-infarcts: odds ratio=0.76, 95% confidence interval=0.68–0.84, p=4.64×10−7. Highly suggestive associations (p0.64) with rs2208454. The association with rs2208454 did not replicate in independent samples of 1822 white and 644 African-American participants, although 4 SNPs within 200kb from rs2208454 were associated with MRI-infarcts in African-American sample. Conclusions This first community-based, genome-wide association study on covert MRI-infarcts uncovered novel associations. Although replication of the association with top SNP failed, possibly due to insufficient power, results in the African American sample are encouraging, and further efforts at replication are needed. PMID:20044523

  14. Abnormal regional brain function in Parkinson's disease: truth or fiction?

    Science.gov (United States)

    Ma, Yilong; Tang, Chengke; Moeller, James R; Eidelberg, David

    2009-04-01

    Normalization of regional measurements by the global mean is commonly employed to minimize inter-subject variability in functional imaging studies. This practice is based on the assumption that global values do not substantially differ between patient and control groups. In this issue of NeuroImage, Borghammer and colleagues challenge the validity of this assumption. They focus on Parkinson's disease (PD) and use computer simulations to show that lower global values can produce spurious increases in subcortical brain regions. The authors speculate that the increased signal observed in these areas in PD is artefactual and unrelated to localized changes in brain function. In this commentary, we summarize what is currently known of the relationship between regional and global metabolic activity in PD and experimental parkinsonism. We found that early stage PD patients exhibit global values that are virtually identical to those of age-matched healthy subjects. SPM analysis revealed increased normalized metabolic activity in a discrete set of biologically relevant subcortical brain regions. Because of their higher variability, the corresponding absolute regional measures did not differ across the two groups. Longitudinal imaging studies in this population showed that the subcortical elevations in normalized metabolism appeared earlier and progressed faster than did focal cortical or global metabolic reductions. The observed increases in subcortical activity, but not the global changes, correlated with independent clinical measures of disease progression. Multivariate analysis with SSM/PCA further confirmed that the abnormal spatial covariance structure of early PD is dominated by these subcortical increases as opposed to network-related reductions in cortical metabolic activity or global changes. Thus, increased subcortical activity in PD cannot be regarded as a simple artefact of global normalization. Moreover, stability of the normalized measurements, particularly at

  15. Automatic segmentation of brain images: selection of region extraction methods

    Science.gov (United States)

    Gong, Leiguang; Kulikowski, Casimir A.; Mezrich, Reuben S.

    1991-07-01

    In automatically analyzing brain structures from a MR image, the choice of low level region extraction methods depends on the characteristics of both the target object and the surrounding anatomical structures in the image. The authors have experimented with local thresholding, global thresholding, and other techniques, using various types of MR images for extracting the major brian landmarks and different types of lesions. This paper describes specifically a local- binary thresholding method and a new global-multiple thresholding technique developed for MR image segmentation and analysis. The initial testing results on their segmentation performance are presented, followed by a comparative analysis of the two methods and their ability to extract different types of normal and abnormal brain structures -- the brain matter itself, tumors, regions of edema surrounding lesions, multiple sclerosis lesions, and the ventricles of the brain. The analysis and experimental results show that the global multiple thresholding techniques are more than adequate for extracting regions that correspond to the major brian structures, while local binary thresholding is helpful for more accurate delineation of small lesions such as those produced by MS, and for the precise refinement of lesion boundaries. The detection of other landmarks, such as the interhemispheric fissure, may require other techniques, such as line-fitting. These experiments have led to the formulation of a set of generic computer-based rules for selecting the appropriate segmentation packages for particular types of problems, based on which further development of an innovative knowledge- based, goal directed biomedical image analysis framework is being made. The system will carry out the selection automatically for a given specific analysis task.

  16. Enhanced regional brain metabolic responses to benzodiazepines in cocaine abusers

    Energy Technology Data Exchange (ETDEWEB)

    Volkow, N.D.; Wang, G.J.; Fowler, J.S. [Brookhaven National Lab., Upton, NY (United States)] [and others

    1997-05-01

    While dopamine (DA) appears to be crucial for cocaine reinforcement, its involvement in cocaine addiction is much less clear. Using PET we have shown persistent reductions in striatal DA D2 receptors (which arc predominantly located on GABA cells) in cocaine abusers. This finding coupled to GABA`s role as an effector for DA led us to investigate if there were GABAergic abnormalities in cocaine abusers. In this study we measured regional brain metabolic responses to lorazepam, to indirectly assess GABA function (benzodiazepines facilitate GABAergic neurotransmission). Methods: The experimental subjects consisted of 12 active cocaine abusers and 32 age matched controls. Each subject underwent two PET FDG scans obtained within 1 week of each other. The first FDG scan was obtained after administration of placebo (3 cc of saline solution) given 40-50 minutes prior to FDG; and the second after administration of lorazepam (30 {mu}g/kg) given 40-50 minutes prior to FDG. The subjects were blind to the drugs received. Results: Lorazepam-induced sleepiness was significantly greater in abusers than in controls (p<0.001). Lorazepam-induced decreases in brain glucose metabolism were significantly larger in cocaine abusers than in controls. Whereas in controls whole brain metabolism decreased 13{+-}7 %, in cocaine abusers it decreased 21{+-}13 % (p < 0.05). Lorazepam-induced decrements in regional metabolism were significantly larger in striatum (p < 0.0 1), thalamus (p < 0.01) and cerebellum (p < 0.005) of cocaine abusers than of controls (ANOVA diagnosis by condition (placebo versus lorazepam) interaction effect). The only brain region for which the absolute metabolic changes-induced by lorazepam in cocaine abusers were equivalent to those in controls was the orbitofrontal cortex. These results document an accentuated sensitivity to benzodiazepines in cocaine abusers which is compatible with disrupted GABAergic function in these patients.

  17. 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.)

  18. Local awakening: regional reorganizations of brain oscillations after sleep.

    Science.gov (United States)

    Tsai, Pei-Jung; Chen, Sharon Chia-Ju; Hsu, Chun-Yao; Wu, Changwei W; Wu, Yu-Chin; Hung, Ching-Sui; Yang, Albert C; Liu, Po-Yu; Biswal, Bharat; Lin, Ching-Po

    2014-11-15

    Brain functions express rhythmic fluctuations accompanied by sleep and wakefulness each day, but how sleep regulates brain rhythms remains unclear. Following the dose-dependent local sleep concept, two succeeding questions emerge: (1) is the sleep regulation a network-specific process; and (2) is the awakening state dependent on the previous sleep stages? To answer the questions, we conducted simultaneous EEG and fMRI recordings over 22 healthy male participants, along pre-sleep, nocturnal sleep and awakening. Using paired comparisons between awakening and pre-sleep conditions, three scenarios of the regional specificity were demonstrated on awakening: (1) the default-mode and hippocampal networks maintained similar connectivity and spectral power; (2) the sensorimotor network presented reduced connectivity and spectral power; and (3) the thalamus demonstrated substantially enhanced connectivity to the neo-cortex with decreased spectral power. With regard to the stage effect, the deep sleep group had significant changes in both functional connectivity and spectral power on awakening, whereas the indices of light sleep group remained relatively quiescent after sleep. The phenomena implied that slow-wave sleep could be key to rebooting the BOLD fluctuations after sleep. In conclusion, the regional specificity and the stage effect were verified in support of the local awakening concept, indicating that sleep regulation leads to the reorganization of brain networks upon awakening.

  19. 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

    2014-12-01

    We examined regional changes in brain volume in healthy adults (N=167, age 19-79years 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 PhG, and individual differences in change were noted in all regions, except the OF. Pro-inflammatory genetic variants modified shrinkage in PhG and CbH. Carriers of two T alleles of interleukin-1β (IL-1β C-511T, rs16944) and a T allele of methylenetetrahydrofolate reductase (MTHFR C677T, 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.

  20. 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.

  1. 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

    2017-05-20

    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.

  2. Dynamic pupillary exchange engages brain regions encoding social salience.

    Science.gov (United States)

    Harrison, Neil A; Gray, Marcus A; Critchley, Hugo D

    2009-01-01

    Covert exchange of autonomic responses may shape social affective behavior, as observed in mirroring of pupillary responses during sadness processing. We examined how, independent of facial emotional expression, dynamic coherence between one's own and another's pupil size modulates regional brain activity. Fourteen subjects viewed pairs of eye stimuli while undergoing fMRI. Using continuous pupillometry biofeedback, the size of the observed pupils was varied, correlating positively or negatively with changes in participants' own pupils. Viewing both static and dynamic stimuli activated right fusiform gyrus. Observing dynamically changing pupils activated STS and amygdala, regions engaged by non-static and salient facial features. Discordance between observed and observer's pupillary changes enhanced activity within bilateral anterior insula, left amygdala and anterior cingulate. In contrast, processing positively correlated pupils enhanced activity within left frontal operculum. Our findings suggest pupillary signals are monitored continuously during social interactions and that incongruent changes activate brain regions involved in tracking motivational salience and attentionally meaningful information. Naturalistically, dynamic coherence in pupillary change follows fluctuations in ambient light. Correspondingly, in social contexts discordant pupil response is likely to reflect divergence of dispositional state. Our data provide empirical evidence for an autonomically mediated extension of forward models of motor control into social interaction.

  3. Using Profiles Based on Nucleotide Hydrophobicity to Define Essential Regions for Splicing

    Directory of Open Access Journals (Sweden)

    Galina Boldina, Anatoly Ivashchenko, Mireille Régnier

    2009-01-01

    Full Text Available The splice-site sequences of U2-type introns are highly degenerate, so many different sequences can function as U2-type splice sites. Using our new profiles based on hydrophobicity properties we pointed out specific properties for regions surrounding splice sites. We built a set T of flanking regions of genes with 1-3 introns from 21st and 22nd chromosomes extracted from GenBank to define positions having conserved properties, namely hydrophobicity, that are potentially essential for recognition by spliceosome. GT–AG introns exist in U2 and U12-types. Therefore, intron type cannot be simply determined by the dinucleotide termini. We attempted to distinguish U2 and U12-types introns with help of hydrophobicity profiles on sets of spice sites for U2 or U12-type introns extracted from SpliceRack database. The positions given by our method, which may be important for recognition by spliceosome, were compared to the nucleotide consensus provided by a classical method, Pictogram. We showed that there is a similarity of hydrophobicity profiles inside intron types. On one hand, GT–AG and GC–AG introns belonging to U2-type have resembling hydrophobicity profiles as well as AT–AC and GT–AG introns belonging to U12-type. On the other hand, hydrophobicity profiles of U2 and U12-types GT–AG introns are completely different. We suggest that hydrophobicity profiles facilitate definition of intron type, distinguishing U2 and U12 intron types and can be used to build programs to search splice site and to evaluate their strength. Therefore, our study proves that hydrophobicity profiles are informative method providing insights into mechanisms of splice sites recognition.

  4. Functional MRI preprocessing in lesioned brains: manual versus automated region of interest analysis

    Directory of Open Access Journals (Sweden)

    Kathleen A Garrison

    2015-09-01

    Full Text Available Functional magnetic resonance imaging has significant potential in the study and treatment of neurological disorders and stroke. Region of interest (ROI analysis in such studies allows for testing of strong a priori clinical hypotheses with improved statistical power. A commonly used automated approach to ROI analysis is to spatially normalize each participant’s structural brain image to a template brain image and define ROIs using an atlas. However, in studies of individuals with structural brain lesions such as stroke, the gold standard approach may be to manually hand-draw ROIs on each participant’s non-normalized structural brain image. Automated approaches to ROI analysis are faster and more standardized, yet are susceptible to preprocessing error (e.g., normalization error that can be greater in lesioned brains. The manual approach to ROI analysis has high demand for time and expertise but may provide a more accurate estimate of brain response. In this study, we directly compare commonly used automated and manual approaches to ROI analysis by reanalyzing data from a previously published hypothesis-driven cognitive fMRI study involving individuals with stroke. The ROI evaluated is the pars opercularis of the inferior frontal gyrus. We found a significant difference in task-related effect size and percent activated voxels in this ROI between the automated and manual approaches to ROI analysis. Task interactions, however, were consistent across ROI analysis approaches. These findings support the use of automated approaches to ROI analysis in studies of lesioned brains, provided they employ a task interaction design.

  5. Functional MRI Preprocessing in Lesioned Brains: Manual Versus Automated Region of Interest Analysis.

    Science.gov (United States)

    Garrison, Kathleen A; Rogalsky, Corianne; Sheng, Tong; Liu, Brent; Damasio, Hanna; Winstein, Carolee J; Aziz-Zadeh, Lisa S

    2015-01-01

    Functional magnetic resonance imaging (fMRI) has significant potential in the study and treatment of neurological disorders and stroke. Region of interest (ROI) analysis in such studies allows for testing of strong a priori clinical hypotheses with improved statistical power. A commonly used automated approach to ROI analysis is to spatially normalize each participant's structural brain image to a template brain image and define ROIs using an atlas. However, in studies of individuals with structural brain lesions, such as stroke, the gold standard approach may be to manually hand-draw ROIs on each participant's non-normalized structural brain image. Automated approaches to ROI analysis are faster and more standardized, yet are susceptible to preprocessing error (e.g., normalization error) that can be greater in lesioned brains. The manual approach to ROI analysis has high demand for time and expertise, but may provide a more accurate estimate of brain response. In this study, commonly used automated and manual approaches to ROI analysis were directly compared by reanalyzing data from a previously published hypothesis-driven cognitive fMRI study, involving individuals with stroke. The ROI evaluated is the pars opercularis of the inferior frontal gyrus. Significant differences were identified in task-related effect size and percent-activated voxels in this ROI between the automated and manual approaches to ROI analysis. Task interactions, however, were consistent across ROI analysis approaches. These findings support the use of automated approaches to ROI analysis in studies of lesioned brains, provided they employ a task interaction design.

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

    Science.gov (United States)

    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

  7. Ethical controversies at end of life after traumatic brain injury: defining death and organ donation.

    Science.gov (United States)

    Souter, Michael; Van Norman, Gail

    2010-09-01

    Death is more than a mere biological occurrence. It has important legal, medical, and social ramifications that make it imperative that those who are responsible for determination of death be accurate and above suspicion. The medical and legal definitions of death have evolved to include consideration of such concepts as loss of integration of the whole organism, loss of autonomy, and loss of personhood. Development of the concept of brain death coincided with advances in medical technology that facilitated artificial ventilation and organ transplantation. More recently, the process of "timed" death with subsequent organ donation (controlled donation after cardiac death transplantation) has raised controversial questions having to do with the limits of treatments that facilitate organ transplant but might hasten death, and the duration of cardiac arrest necessary for declaration of death and the commencement of organ procurement. In this review, we discuss the background and ethical ramifications of the concepts of brain death, and of controversies involved in controlled donation after cardiac death organ transplantation.

  8. Cortical hypoexcitation defines neuronal responses in the immediate aftermath of traumatic brain injury.

    Directory of Open Access Journals (Sweden)

    Victoria Philippa Anne Johnstone

    Full Text Available Traumatic brain injury (TBI from a blow to the head is often associated with complex patterns of brain abnormalities that accompany deficits in cognitive and motor function. Previously we reported that a long-term consequence of TBI, induced with a closed-head injury method modelling human car and sporting accidents, is neuronal hyper-excitation in the rat sensory barrel cortex that receives tactile input from the face whiskers. Hyper-excitation occurred only in supra-granular layers and was stronger to complex than simple stimuli. We now examine changes in the immediate aftermath of TBI induced with same injury method. At 24 hours post-trauma significant sensorimotor deficits were observed and characterisation of the cortical population neuronal responses at that time revealed a depth-dependent suppression of neuronal responses, with reduced responses from supragranular layers through to input layer IV, but not in infragranular layers. In addition, increased spontaneous firing rate was recorded in cortical layers IV and V. We postulate that this early post-injury suppression of cortical processing of sensory input accounts for immediate post-trauma sensory morbidity and sets into train events that resolve into long-term cortical hyper-excitability in upper sensory cortex layers that may account for long-term sensory hyper-sensitivity in humans with TBI.

  9. Brain size and visual environment predict species differences in paper wasp sensory processing brain regions (hymenoptera: vespidae, polistinae).

    Science.gov (United States)

    O'Donnell, Sean; Clifford, Marie R; DeLeon, Sara; Papa, Christopher; Zahedi, Nazaneen; Bulova, Susan J

    2013-01-01

    The mosaic brain evolution hypothesis predicts that the relative volumes of functionally distinct brain regions will vary independently and correlate with species' ecology. Paper wasp species (Hymenoptera: Vespidae, Polistinae) differ in light exposure: they construct open versus enclosed nests and one genus (Apoica) is nocturnal. We asked whether light environments were related to species differences in the size of antennal and optic processing brain tissues. Paper wasp brains have anatomically distinct peripheral and central regions that process antennal and optic sensory inputs. We measured the volumes of 4 sensory processing brain regions in paper wasp species from 13 Neotropical genera including open and enclosed nesters, and diurnal and nocturnal species. Species differed in sensory region volumes, but there was no evidence for trade-offs among sensory modalities. All sensory region volumes correlated with brain size. However, peripheral optic processing investment increased with brain size at a higher rate than peripheral antennal processing investment. Our data suggest that mosaic and concerted (size-constrained) brain evolution are not exclusive alternatives. When brain regions increase with brain size at different rates, these distinct allometries can allow for differential investment among sensory modalities. As predicted by mosaic evolution, species ecology was associated with some aspects of brain region investment. Nest architecture variation was not associated with brain investment differences, but the nocturnal genus Apoica had the largest antennal:optic volume ratio in its peripheral sensory lobes. Investment in central processing tissues was not related to nocturnality, a pattern also noted in mammals. The plasticity of neural connections in central regions may accommodate evolutionary shifts in input from the periphery with relatively minor changes in volume.

  10. 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.

  11. Acetamiprid Accumulates in Different Amounts in Murine Brain Regions

    Science.gov (United States)

    Terayama, Hayato; Endo, Hitoshi; Tsukamoto, Hideo; Matsumoto, Koichi; Umezu, Mai; Kanazawa, Teruhisa; Ito, Masatoshi; Sato, Tadayuki; Naito, Munekazu; Kawakami, Satoshi; Fujino, Yasuhiro; Tatemichi, Masayuki; Sakabe, Kou

    2016-01-01

    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. PMID:27669271

  12. Regional energy balance in rat brain after transient forebrain ischemia.

    Science.gov (United States)

    Pulsinelli, W A; Duffy, T E

    1983-05-01

    Phosphocreatine, ATP, and glucose were severely depleted, and the lactate levels were increased in the paramedian neocortex, dorsal-lateral striatum, and CA1 zone of hippocampus of rats exposed to 30 min of forebrain ischemia. Upon recirculation of the brain, phosphocreatine, ATP, and lactate concentrations recovered to control values in the paramedian neocortex and CA1 zone of hippocampus and to near-control values in the striatum. The phosphocreatine and ATP concentrations then fell and the lactate levels rose in the striatum after 6-24 h, and in the CA1 zone of hippocampus after 24-72 h. The initial recovery and subsequent delayed changes in the phosphocreatine, ATP, and lactate concentrations in the striatum and hippocampus coincided with the onset and progression of morphological injury in these brain regions. The results suggest that cells in these regions regain normal or near-normal mitochondrial function and are viable, in terms of energy production, for many hours before unknown mechanisms cause irreversible neuronal before unknown mechanisms cause irreversible neuronal injury.

  13. Interspecific allometry of the brain and brain regions in parrots (psittaciformes): comparisons with other birds and primates.

    Science.gov (United States)

    Iwaniuk, Andrew N; Dean, Karen M; Nelson, John E

    2005-01-01

    Despite significant progress in understanding the evolution of the mammalian brain, relatively little is known of the patterns of evolutionary change in the avian brain. In particular, statements regarding which avian taxa have relatively larger brains and brain regions are based on small sample sizes and statistical analyses are generally lacking. We tested whether psittaciforms (parrots, cockatoos and lorikeets) have larger brains and forebrains than other birds using both conventional and phylogenetically based methods. In addition, we compared the psittaciforms to primates to determine if cognitive similarities between the two groups were reflected by similarities in brain and telencephalic volumes. Overall, psittaciforms have relatively larger brains and telencephala than most other non-passerine orders. No significant difference in relative brain or telencephalic volume was detected between psittaciforms and passerines. Comparisons of other brain region sizes between psittaciforms and other birds, however, exhibited conflicting results depending upon whether body mass or a brain volume remainder (total brain volume - brain region volume) was used as a scaling variable. When compared to primates, psittaciforms possessed similar relative brain and telencephalic volumes. The only exception to this was that in some analyses psittaciforms had significantly larger telencephala than primates of similar brain volume. The results therefore provide empirical evidence for previous claims that psittaciforms possess relatively large brains and telencephala. Despite the variability in the results, it is clear that psittaciforms tend to possess large brains and telencephala relative to non-passerines and are similar to primates in this regard. Although it could be suggested that this reflects the advanced cognitive abilities of psittaciforms, similar studies performed in corvids and other avian taxa will be required before this claim can be made with any certainty.

  14. Real-time fMRI brain computer interfaces: self-regulation of single brain regions to networks.

    Science.gov (United States)

    Ruiz, Sergio; Buyukturkoglu, Korhan; Rana, Mohit; Birbaumer, Niels; Sitaram, Ranganatha

    2014-01-01

    With the advent of brain computer interfaces based on real-time fMRI (rtfMRI-BCI), the possibility of performing neurofeedback based on brain hemodynamics has become a reality. In the early stage of the development of this field, studies have focused on the volitional control of activity in circumscribed brain regions. However, based on the understanding that the brain functions by coordinated activity of spatially distributed regions, there have recently been further developments to incorporate real-time feedback of functional connectivity and spatio-temporal patterns of brain activity. The present article reviews the principles of rtfMRI neurofeedback, its applications, benefits and limitations. A special emphasis is given to the discussion of novel developments that have enabled the use of this methodology to achieve self-regulation of the functional connectivity between different brain areas and of distributed brain networks, anticipating new and exciting applications for cognitive neuroscience and for the potential alleviation of neuropsychiatric disorders.

  15. Defining the Optimal Planning Target Volume in Image-Guided Stereotactic Radiosurgery of Brain Metastases: Results of a Randomized Trial

    Energy Technology Data Exchange (ETDEWEB)

    Kirkpatrick, John P., E-mail: john.kirkpatrick@dm.duke.edu [Department of Radiation Oncology, Duke University, Durham, North Carolina (United States); Department of Surgery, Duke University, Durham, North Carolina (United States); Wang, Zhiheng [Department of Radiation Oncology, Duke University, Durham, North Carolina (United States); Sampson, John H. [Department of Radiation Oncology, Duke University, Durham, North Carolina (United States); Department of Surgery, Duke University, Durham, North Carolina (United States); McSherry, Frances; Herndon, James E. [Department of Biostatistics and Bioinformatics, Duke University, Durham, North Carolina (United States); Allen, Karen J.; Duffy, Eileen [Department of Radiation Oncology, Duke University, Durham, North Carolina (United States); Hoang, Jenny K. [Department of Radiology, Duke University, Durham, North Carolina (United States); Chang, Zheng; Yoo, David S.; Kelsey, Chris R.; Yin, Fang-Fang [Department of Radiation Oncology, Duke University, Durham, North Carolina (United States)

    2015-01-01

    Purpose: To identify an optimal margin about the gross target volume (GTV) for stereotactic radiosurgery (SRS) of brain metastases, minimizing toxicity and local recurrence. Methods and Materials: Adult patients with 1 to 3 brain metastases less than 4 cm in greatest dimension, no previous brain radiation therapy, and Karnofsky performance status (KPS) above 70 were eligible for this institutional review board–approved trial. Individual lesions were randomized to 1- or 3- mm uniform expansion of the GTV defined on contrast-enhanced magnetic resonance imaging (MRI). The resulting planning target volume (PTV) was treated to 24, 18, or 15 Gy marginal dose for maximum PTV diameters less than 2, 2 to 2.9, and 3 to 3.9 cm, respectively, using a linear accelerator–based image-guided system. The primary endpoint was local recurrence (LR). Secondary endpoints included neurocognition Mini-Mental State Examination, Trail Making Test Parts A and B, quality of life (Functional Assessment of Cancer Therapy-Brain), radionecrosis (RN), need for salvage radiation therapy, distant failure (DF) in the brain, and overall survival (OS). Results: Between February 2010 and November 2012, 49 patients with 80 brain metastases were treated. The median age was 61 years, the median KPS was 90, and the predominant histologies were non–small cell lung cancer (25 patients) and melanoma (8). Fifty-five, 19, and 6 lesions were treated to 24, 18, and 15 Gy, respectively. The PTV/GTV ratio, volume receiving 12 Gy or more, and minimum dose to PTV were significantly higher in the 3-mm group (all P<.01), and GTV was similar (P=.76). At a median follow-up time of 32.2 months, 11 patients were alive, with median OS 10.6 months. LR was observed in only 3 lesions (2 in the 1 mm group, P=.51), with 6.7% LR 12 months after SRS. Biopsy-proven RN alone was observed in 6 lesions (5 in the 3-mm group, P=.10). The 12-month DF rate was 45.7%. Three months after SRS, no significant change in

  16. Phylogenetic origins of early alterations in brain region proportions.

    Science.gov (United States)

    Charvet, Christine J; Sandoval, Alexis L; Striedter, Georg F

    2010-01-01

    Adult galliform birds (e.g. chickens) exhibit a relatively small telencephalon and a proportionately large optic tectum compared with parrots and songbirds. We previously examined the embryonic origins of these adult species differences and found that the optic tectum is larger in quail than in parakeets and songbirds at early stages of development, prior to tectal neurogenesis onset. The aim of this study was to determine whether a proportionately large presumptive tectum is a primitive condition within birds or a derived feature of quail and other galliform birds. To this end, we examined embryonic brains of several avian species (emus, parrots, songbirds, waterfowl, galliform birds), reptiles (3 lizard species, alligators, turtles) and a monotreme (platypuses). Brain region volumes were estimated from serial Nissl-stained sections. We found that the embryos of galliform birds and lizards exhibit a proportionally larger presumptive tectum than all the other examined species. The presumptive tectum of the platypus is unusually small. The most parsimonious interpretation of these data is that the expanded embryonic tectum of lizards and galliform birds is a derived feature in both of these taxonomic groups.

  17. Copper pathology in vulnerable brain regions in Parkinson's disease.

    Science.gov (United States)

    Davies, Katherine M; Bohic, Sylvain; Carmona, Asunción; Ortega, Richard; Cottam, Veronica; Hare, Dominic J; Finberg, John P M; Reyes, Stefanie; Halliday, Glenda M; Mercer, Julian F B; Double, Kay L

    2014-04-01

    Synchrotron-based x-ray fluorescence microscopy, immunofluorescence, and Western blotting were used to investigate changes in copper (Cu) and Cu-associated pathways in the vulnerable substantia nigra (SN) and locus coeruleus (LC) and in nondegenerating brain regions in cases of Parkinson's disease (PD) and appropriate healthy and disease controls. In PD and incidental Lewy body disease, levels of Cu and Cu transporter protein 1, were significantly reduced in surviving neurons in the SN and LC. Specific activity of the cuproprotein superoxide dismutase 1 was unchanged in the SN in PD but was enhanced in the parkinsonian anterior cingulate cortex, a region with α-synuclein pathology, normal Cu, and limited cell loss. These data suggest that regions affected by α-synuclein pathology may display enhanced vulnerability and cell loss if Cu-dependent protective mechanisms are compromised. Additional investigation of copper pathology in PD may identify novel targets for the development of protective therapies for this disorder. Copyright © 2014 Elsevier Inc. All rights reserved.

  18. Defining regions of interest using cross-frequency coupling in extratemporal lobe epilepsy patients

    Science.gov (United States)

    Guirgis, Mirna; Chinvarun, Yotin; del Campo, Martin; Carlen, Peter L.; Bardakjian, Berj L.

    2015-04-01

    Objective. Clinicians identify seizure onset zones (SOZs) for resection in an attempt to localize the epileptogenic zone (EZ), which is the cortical tissue that is indispensible for seizure generation. An automated system is proposed to objectively localize this EZ by identifying regions of interest (ROIs). Methods. Intracranial electroencephalogram recordings were obtained from seven patients presenting with extratemporal lobe epilepsy and the interaction between neuronal rhythms in the form of phase-amplitude coupling was investigated. Modulation of the amplitude of high frequency oscillations (HFOs) by the phase of low frequency oscillations was measured by computing the modulation index (MI). Delta- (0.5-4 Hz) and theta- (4-8 Hz) modulation of HFOs (30-450 Hz) were examined across the channels of a 64-electrode subdural grid. Surrogate analysis was performed and false discovery rates were computed to determine the significance of the modulation observed. Mean MI values were subjected to eigenvalue decomposition (EVD) and channels defining the ROIs were selected based on the components of the eigenvector corresponding to the largest eigenvalue. ROIs were compared to the SOZs identified by two independent neurologists. Global coherence values were also computed. Main results. MI was found to capture the seizure in time for six of seven patients and identified ROIs in all seven. Patients were found to have a poorer post-surgical outcome when the number of EVD-selected channels that were not resected increased. Moreover, in patients who experienced a seizure-free outcome (i.e., Engel Class I) all EVD-selected channels were found to be within the resected tissue or immediately adjacent to it. In these Engel Class I patients, delta-modulated HFOs were found to identify more of the channels in the resected tissue compared to theta-modulated HFOs. However, for the Engel Class IV patient, the delta-modulated HFOs did not identify any of the channels in the resected

  19. 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.

  20. Defining the spatial scale in modern regional analysis new challenges from data at local level

    CERN Document Server

    Fernández Vázquez, Esteban

    2014-01-01

    This book discusses the concept of region, including techniques of ecological inference applied to estimating disaggregated data from observable aggregates. The final part presents applications in line with the functional areas definition in regional analysis.

  1. Regional protein synthesis in rat brain following acute hemispheric ischemia.

    Science.gov (United States)

    Dienel, G A; Pulsinelli, W A; Duffy, T E

    1980-11-01

    Regional protein synthesis was measured in rat brain at intervals up to 48 h following occlusion of the four major arteries to the brain for either 10 or 30 min. Four-vessel occlusions produces ischemia in the cerebral hemispheres and oligemia in the midbrain-diencephalon and brainstem. During the hour following 10 min of ischemia, protein synthesis, measured by incorporation of [14C]valine into protein, was inhibited in the cerebral cortex by 67%. Normal rates of protein synthesis were attained within 4 h of recirculation. In rats subjected to 30 min of ischemia, protein synthesis was inhibited by 83% during the first hour of recirculation in the cortex, caudate-putamen, and hippocampus. Recovery of protein synthesis in these regions was slow (25-48 h). The midbrain-diencephalon showed less inhibition, 67%, and faster recovery (by 12 h). Protein synthesis was unaffected in the brainstem. [14C]Autoradiography revealed that the pyramidal neurons of the hippocampus and areas of the caudate and cortex failed to recover normal rates of protein synthesis even after 48 h. The accumulation of TCA-soluble [14C]valine was enhanced (55-65%) in the cortex, caudate, and hippocampus after 30 min of ischemia; the increase persisted for 12 h. A smaller rise in [14C]valine content (30%) and more rapid normalization of valine accumulation (by 7 h) were observed in the midbrain-diencephalon; no changes were found in the brainstem. In the cortex, recovery was more rapid when the duration of ischemia was reduced. Thus, the degree of inhibition of protein synthesis, the accumulation of valine in the tissue, and the length of time required to reestablish normal values for these processes were dependent on both the severity and the duration of the ischemic insult. Restoration of normal rates of protein synthesis after ischemia was slow compared with the normalization of cerebral energy metabolites.

  2. Regional brain responses in nulliparous women to emotional infant stimuli.

    Directory of Open Access Journals (Sweden)

    Jessica L Montoya

    Full Text Available Infant cries and facial expressions influence social interactions and elicit caretaking behaviors from adults. Recent neuroimaging studies suggest that neural responses to infant stimuli involve brain regions that process rewards. However, these studies have yet to investigate individual differences in tendencies to engage or withdraw from motivationally relevant stimuli. To investigate this, we used event-related fMRI to scan 17 nulliparous women. Participants were presented with novel infant cries of two distress levels (low and high and unknown infant faces of varying affect (happy, sad, and neutral in a randomized, counter-balanced order. Brain activation was subsequently correlated with scores on the Behavioral Inhibition System/Behavioral Activation System scale. Infant cries activated bilateral superior and middle temporal gyri (STG and MTG and precentral and postcentral gyri. Activation was greater in bilateral temporal cortices for low- relative to high-distress cries. Happy relative to neutral faces activated the ventral striatum, caudate, ventromedial prefrontal, and orbitofrontal cortices. Sad versus neutral faces activated the precuneus, cuneus, and posterior cingulate cortex, and behavioral activation drive correlated with occipital cortical activations in this contrast. Behavioral inhibition correlated with activation in the right STG for high- and low-distress cries relative to pink noise. Behavioral drive correlated inversely with putamen, caudate, and thalamic activations for the comparison of high-distress cries to pink noise. Reward-responsiveness correlated with activation in the left precentral gyrus during the perception of low-distress cries relative to pink noise. Our findings indicate that infant cry stimuli elicit activations in areas implicated in auditory processing and social cognition. Happy infant faces may be encoded as rewarding, whereas sad faces activate regions associated with empathic processing. Differences

  3. 10 CFR 72.100 - Defining potential effects of the ISFSI or MRS on the region.

    Science.gov (United States)

    2010-01-01

    ... in the region resulting from the release of radioactive materials under normal and accident... unusual regional and site characteristics shall be taken into account. (b) Each site must be evaluated with respect to the effects on the regional environment resulting from construction, operation, and...

  4. 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.

  5. 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

  6. 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...

  7. A candidate region for Nevoid Basal Cell Carcinoma Syndrome defined by genetic and physical mapping

    Energy Technology Data Exchange (ETDEWEB)

    Wainwright, B.; Negus, K.; Berkman, J. [Univ. of Queensland, Brisbane (Australia)] [and others

    1994-09-01

    Nevoid Basal Cell Carcinoma Syndrome (NBCCS, or Gorlin`s syndrome) is a cancer predisposition syndrome charcterized by multiple basal cell carcinomas (BCCs) and diverse developmental defects. The gene responsible for NBCCS, which is most likely to be a tumor suppressor gene, has previously been mapped to 9q22.3-q31 in a 12 cM interval between the microsatellite marker loci D9S12 and D9S109. Combined multipoint and haplotype analyses of Australian pedigrees has further refined the localization to a 2 cM interval between markers D9S196 and D9S180. Our loss of heterozygosity (LOH) studies from sporadic (n= 58) and familial (n=41) BCCs indicate that 50% have deletions within the NBCCS candidate region. All LOH is consistent with the genetic mapping of the NBCCS locus. Additionally, one sporadic tumor indicates that the smallest region of overlap in the deletions is within the interval D9S287 (proximal) and D9S180 (distal). A series of YAC clones from within this region has been mapped by FISH to examine chimerism. These clones, which have been mapped with respect to one another, form a contig which encompasses the candidate region from D9S196 to D9S180.

  8. 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.)

  9. 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...

  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.

  11. 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.

  12. 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.

  13. 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.

  14. Geothermal GIS coverage of the Great Basin, USA: Defining regional controls and favorable exploration terrains

    Science.gov (United States)

    Coolbaugh, M.F.; Sawatzky, D.L.; Oppliger, G.L.; Minor, T.B.; Raines, G.L.; Shevenell, L.; Blewitt, G.; Louie, J.N.

    2003-01-01

    A geographic information system (GIS) of geothermal resources, built last year for the state of Nevada, is being expanded to cover the Great Basin, USA. Data from that GIS is being made available to industry, other researchers, and the public via a web site at the Great Basin Center for Geothermal Energy, Reno, Nevada. That web site features a search engine, supports ArcExplorer?? for on-line map construction, and provides downloadable data layers in several formats. Though data collection continues, preliminary analysis has begun. Contour maps of geothermal temperatures, constructed using geothermometer temperatures calculated from a Great Basin geochemical database compiled by the Geo-Heat Center, reveal distinctive trends and patterns. As expected, magmatic-type and extensional-type geothermal systems have profoundly different associations, with magmatic-type systems following major tectonic boundaries, and extensional-type systems associating with regionally high heat flow, thin crust, active faulting, and high extensional strain rates. As described by earlier researchers, including Rowen and Wetlaufer (1981) and Koenig and McNitt (1983), high-temperature (> 100??C) geothermal systems appear to follow regional northeast trends, most conspicuously including the Humboldt structural zone in Nevada, the "Black Rock-Alvord Desert" trend in Oregon and Nevada, and the "Newcastle-Roosevelt" trend in Utah and Nevada. Weights-of-evidence analyses confirm a preference of high-temperature geothermal systems for young northeast-trending faults, but the distribution of geothermal systems correlates even better with high rates of crustal extension, as measured from global positioning system (GPS) stations in Nevada. A predictive map of geothermal potential based only on areas of high extensional strain rates and high heat flux does an excellent job of regionally predicting the location of most known geothermal systems in Nevada, and may prove useful in identifying blind

  15. CAGE-defined promoter regions of the genes implicated in Rett Syndrome

    DEFF Research Database (Denmark)

    Vitezic, Morana; Bertin, Nicolas; Andersson, Robin;

    2014-01-01

    BACKGROUND: Mutations in three functionally diverse genes cause Rett Syndrome. Although the functions of Forkhead box G1 (FOXG1), Methyl CpG binding protein 2 (MECP2) and Cyclin-dependent kinase-like 5 (CDKL5) have been studied individually, not much is known about their relation to each other...... for each gene and the common transcription factors likely to regulate the three genes. Our data imply Polycomb Repressive Complex 2 (PRC2) mediated silencing of Foxg1 in cerebellum CONCLUSIONS: Our analyses provide a comprehensive picture of the regulatory regions of the three genes involved in Rett...... Syndrome....

  16. The Characterization Of The Kinetics Of Chlamydia Muridarum Infection In Defined Regions Of The Murine Genital Tract

    Science.gov (United States)

    2008-08-01

    pathological sequelae including pelvic inflammatory disease and infertility . The continued increase in incidence rates of genital chlamydial infection over...bacterial numbers from vaginal swab material to assess the kinetics of infection. Given the differences in tissue anatomy, hormonal regulation, and immune...provide in-depth insight into the kinetics of genital Chlamydia muridarum infection in defined regions of the murine female reproductive tract. vi

  17. Defining a Canadian approach to municipal consolidation in major city-regions

    Directory of Open Access Journals (Sweden)

    Jim Lightbody

    2009-05-01

    Full Text Available Where there is a central government with an exclusive mandate over municipalities, along with a state executive structure using the Westminster model, then the consolidation of squabbling municipalities within metropolitan boundaries becomes a distinct possibility A general model of municipal restructuring for the Canadian metropolis is more widespread than the superficially unique circumstances of each case might suggest. The thinking here is informed by Clarence Stone’s urban regime model, which helps to clarify what influences constituted the political tipping point for central government action. The paper focuses primarily on the Toronto and Montreal city-regional municipal consolidations at the end of the last century. It is argued that the decisive element in setting the stage for significant change lay in the pervasive influence of corporate Canada in generally shaping provincial political discourse. What has not previously been of much interest for investigators is the matter of direct consequences for the low politics of city-regional governance. As will be seen, they were both tangible and considerable.

  18. 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.

  19. Multicolor fluorescent in situ hybridization to define abutting and overlapping gene expression in the embryonic zebrafish brain

    Directory of Open Access Journals (Sweden)

    Hauptmann Giselbert

    2011-04-01

    Full Text Available Abstract Background In recent years, mapping of overlapping and abutting regulatory gene expression domains by chromogenic two-color in situ hybridization has helped define molecular subdivisions of the developing vertebrate brain and shed light on its basic organization. Despite the benefits of this technique, visualization of overlapping transcript distributions by differently colored precipitates remains difficult because of masking of lighter signals by darker color precipitates and lack of three-dimensional visualization properties. Fluorescent detection of transcript distributions may be able to solve these issues. However, despite the use of signal amplification systems for increasing sensitivity, fluorescent detection in whole-mounts suffers from rapid quenching of peroxidase (POD activity compared to alkaline phosphatase chromogenic reactions. Thus, less strongly expressed genes cannot be efficiently detected. Results We developed an optimized procedure for fluorescent detection of transcript distribution in whole-mount zebrafish embryos using tyramide signal amplification (TSA. Conditions for hybridization and POD-TSA reaction were optimized by the application of the viscosity-increasing polymer dextran sulfate and the use of the substituted phenol compounds 4-iodophenol and vanillin as enhancers of POD activity. In combination with highly effective bench-made tyramide substrates, these improvements resulted in dramatically increased signal-to-noise ratios. The strongly enhanced signal intensities permitted fluorescent visualization of less abundant transcripts of tissue-specific regulatory genes. When performing multicolor fluorescent in situ hybridization (FISH experiments, the highly sensitive POD reaction conditions required effective POD inactivation after each detection cycle by glycine-hydrochloric acid treatment. This optimized FISH procedure permitted the simultaneous fluorescent visualization of up to three unique transcripts

  20. 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.

  1. A novel approach for locating mice brain regions of Cryptococcus neoformans CNS invasion

    Directory of Open Access Journals (Sweden)

    Chunting He

    2016-04-01

    Full Text Available Aim of this study was to locate the brain regions where Cryptococcus interact with brain cells and invade into brain. After 7 days of intratracheal inocula-tion of GFP-tagged Cryptococcus neoformans strains H99, serial cryosections (10 μm from 3 C57 BL/6 J mice brains were imaged with immunofluorescence microscopy. GFP-tagged H99 were found in some brain regions such as primary motor cortex-secondary motor cortex, caudate putamen, stratum lucidum of hippocampus, field CA1 of hippocampus, dorsal lateral geniculate nucleus, lateral posterior thalamic nucleus, laterorostral part, lateral posterior thalamic nucleus, mediorostral part, retrosplenial agranular cortex, lateral area of secondary visual cortex, and lacunosum molecular layer of the hippocampus. The results will be very useful for further exploring the mechanism of C. neoformans infection of brain.

  2. The robo-pigeon based on the multiple brain regions synchronization implanted microelectrodes.

    Science.gov (United States)

    Huai, Rui-Tuo; Yang, Jun-Qing; Wang, Hui

    2016-07-03

    Almost all multichannel microelectrodes are only applied to the same nucleus. The multiple brain regions synchronization implanted microelectrodes can be implanted in the several brain regions at the same time, when used in the robo-animal, which can reduce the operation process, shorten animals operation time. Due to electrode position relatively fixed, errors caused by each separately implanted electrode were reduced and the animal control effect was greatly increased compared to the original electrodes. The electrode fixed time was also extended. This microelectrode provided beneficial reference function for the study of the free state of small animals in different brain regions.

  3. Regional and cellular gene expression changes in human Huntington's disease brain

    OpenAIRE

    2006-01-01

    Huntington's disease (HD) pathology is well understood at a histological level but a comprehensive molecular analysis of the effect of the disease in the human brain has not previously been available. To elucidate the molecular phenotype of HD on a genome-wide scale, we compared mRNA profiles from 44 human HD brains with those from 36 unaffected controls using microarray analysis. Four brain regions were analyzed: caudate nucleus, cerebellum, prefrontal association cortex [Brodmann's area 9 (...

  4. Spatial analyses of benthic habitats to define coral reef ecosystem regions and potential biogeographic boundaries along a latitudinal gradient.

    Directory of Open Access Journals (Sweden)

    Brian K Walker

    Full Text Available Marine organism diversity typically attenuates latitudinally from tropical to colder climate regimes. Since the distribution of many marine species relates to certain habitats and depth regimes, mapping data provide valuable information in the absence of detailed ecological data that can be used to identify and spatially quantify smaller scale (10 s km coral reef ecosystem regions and potential physical biogeographic barriers. This study focused on the southeast Florida coast due to a recognized, but understudied, tropical to subtropical biogeographic gradient. GIS spatial analyses were conducted on recent, accurate, shallow-water (0-30 m benthic habitat maps to identify and quantify specific regions along the coast that were statistically distinct in the number and amount of major benthic habitat types. Habitat type and width were measured for 209 evenly-spaced cross-shelf transects. Evaluation of groupings from a cluster analysis at 75% similarity yielded five distinct regions. The number of benthic habitats and their area, width, distance from shore, distance from each other, and LIDAR depths were calculated in GIS and examined to determine regional statistical differences. The number of benthic habitats decreased with increasing latitude from 9 in the south to 4 in the north and many of the habitat metrics statistically differed between regions. Three potential biogeographic barriers were found at the Boca, Hillsboro, and Biscayne boundaries, where specific shallow-water habitats were absent further north; Middle Reef, Inner Reef, and oceanic seagrass beds respectively. The Bahamas Fault Zone boundary was also noted where changes in coastal morphologies occurred that could relate to subtle ecological changes. The analyses defined regions on a smaller scale more appropriate to regional management decisions, hence strengthening marine conservation planning with an objective, scientific foundation for decision making. They provide a framework

  5. Regional characterization of longitudinal DT-MRI to study white matter maturation of the early developing brain.

    Science.gov (United States)

    Sadeghi, Neda; Prastawa, Marcel; Fletcher, P Thomas; Wolff, Jason; Gilmore, John H; Gerig, Guido

    2013-03-01

    The human brain undergoes rapid and dynamic development early in life. Assessment of brain growth patterns relevant to neurological disorders and disease requires a normative population model of growth and variability in order to evaluate deviation from typical development. In this paper, we focus on maturation of brain white matter as shown in diffusion tensor MRI (DT-MRI), measured by fractional anisotropy (FA), mean diffusivity (MD), as well as axial and radial diffusivities (AD, RD). We present a novel methodology to model temporal changes of white matter diffusion from longitudinal DT-MRI data taken at discrete time points. Our proposed framework combines nonlinear modeling of trajectories of individual subjects, population analysis, and testing for regional differences in growth pattern. We first perform deformable mapping of longitudinal DT-MRI of healthy infants imaged at birth, 1 year, and 2 years of age, into a common unbiased atlas. An existing template of labeled white matter regions is registered to this atlas to define anatomical regions of interest. Diffusivity properties of these regions, presented over time, serve as input to the longitudinal characterization of changes. We use non-linear mixed effect (NLME) modeling where temporal change is described by the Gompertz function. The Gompertz growth function uses intuitive parameters related to delay, rate of change, and expected asymptotic value; all descriptive measures which can answer clinical questions related to quantitative analysis of growth patterns. Results suggest that our proposed framework provides descriptive and quantitative information on growth trajectories that can be interpreted by clinicians using natural language terms that describe growth. Statistical analysis of regional differences between anatomical regions which are known to mature differently demonstrates the potential of the proposed method for quantitative assessment of brain growth and differences thereof. This will

  6. Regional selection of the brain size regulating gene CASC5 provides new insight into human brain evolution.

    Science.gov (United States)

    Shi, Lei; Hu, Enzhi; Wang, Zhenbo; Liu, Jiewei; Li, Jin; Li, Ming; Chen, Hua; Yu, Chunshui; Jiang, Tianzi; Su, Bing

    2017-02-01

    Human evolution is marked by a continued enlargement of the brain. Previous studies on human brain evolution focused on identifying sequence divergences of brain size regulating genes between humans and nonhuman primates. However, the evolutionary pattern of the brain size regulating genes during recent human evolution is largely unknown. We conducted a comprehensive analysis of the brain size regulating gene CASC5 and found that in recent human evolution, CASC5 has accumulated many modern human specific amino acid changes, including two fixed changes and six polymorphic changes. Among human populations, 4 of the 6 amino acid polymorphic sites have high frequencies of derived alleles in East Asians, but are rare in Europeans and Africans. We proved that this between-population allelic divergence was caused by regional Darwinian positive selection in East Asians. Further analysis of brain image data of Han Chinese showed significant associations of the amino acid polymorphic sites with gray matter volume. Hence, CASC5 may contribute to the morphological and structural changes of the human brain during recent evolution. The observed between-population divergence of CASC5 variants was driven by natural selection that tends to favor a larger gray matter volume in East Asians.

  7. Differential expression of inflammatory mediators in rat microglia cultured from different brain regions

    NARCIS (Netherlands)

    Ren, LQ; Lubrich, B; Biber, K; Gebicke-Haerter, PJ

    1999-01-01

    Microglial cells show a rather uniform distribution of cell numbers throughout the brain with only minor prevalences in some brain regions. Their in situ morphologies, however, may vary markedly from elongated forms observed in apposition with neuronal fibers to spherical cell bodies with sometimes

  8. Acute, regional inflammatory response after traumatic brain injury: Implications for cellular therapy

    OpenAIRE

    Harting, Matthew T.; jimenez, fernando; Adams, Sasha D.; Mercer, David W.; Cox, Charles S.

    2008-01-01

    While cellular therapy has shown promise in the management of traumatic brain injury (TBI), microenvironment interactions between the intracerebral milieu and therapeutic stem cells are poorly understood. We sought to characterize the acute, regional inflammatory response after TBI.

  9. DCE-MRI defined subvolumes of a brain metastatic lesion by principle component analysis and fuzzy-c-means clustering for response assessment of radiation therapy

    Energy Technology Data Exchange (ETDEWEB)

    Farjam, Reza; Tsien, Christina I.; Lawrence, Theodore S. [Department of Radiation Oncology, University of Michigan, 1500 East Medical Center Drive, SPC 5010, Ann Arbor, Michigan 48109-5010 (United States); Cao, Yue, E-mail: yuecao@umich.edu [Department of Radiation Oncology, University of Michigan, 1500 East Medical Center Drive, SPC 5010, Ann Arbor, Michigan 48109-5010 (United States); Department of Radiology, University of Michigan, 1500 East Medical Center Drive, Med Inn Building C478, Ann Arbor, Michigan 48109-5842 (United States); Department of Biomedical Engineering, University of Michigan, 2200 Bonisteel Boulevard, Ann Arbor, Michigan 48109-2099 (United States)

    2014-01-15

    Purpose: To develop a pharmacokinetic modelfree framework to analyze the dynamic contrast enhanced magnetic resonance imaging (DCE-MRI) data for assessment of response of brain metastases to radiation therapy. Methods: Twenty patients with 45 analyzable brain metastases had MRI scans prior to whole brain radiation therapy (WBRT) and at the end of the 2-week therapy. The volumetric DCE images covering the whole brain were acquired on a 3T scanner with approximately 5 s temporal resolution and a total scan time of about 3 min. DCE curves from all voxels of the 45 brain metastases were normalized and then temporally aligned. A DCE matrix that is constructed from the aligned DCE curves of all voxels of the 45 lesions obtained prior to WBRT is processed by principal component analysis to generate the principal components (PCs). Then, the projection coefficient maps prior to and at the end of WBRT are created for each lesion. Next, a pattern recognition technique, based upon fuzzy-c-means clustering, is used to delineate the tumor subvolumes relating to the value of the significant projection coefficients. The relationship between changes in different tumor subvolumes and treatment response was evaluated to differentiate responsive from stable and progressive tumors. Performance of the PC-defined tumor subvolume was also evaluated by receiver operating characteristic (ROC) analysis in prediction of nonresponsive lesions and compared with physiological-defined tumor subvolumes. Results: The projection coefficient maps of the first three PCs contain almost all response-related information in DCE curves of brain metastases. The first projection coefficient, related to the area under DCE curves, is the major component to determine response while the third one has a complimentary role. In ROC analysis, the area under curve of 0.88 ± 0.05 and 0.86 ± 0.06 were achieved for the PC-defined and physiological-defined tumor subvolume in response assessment. Conclusions: The PC-defined

  10. Gene expression in the rodent brain is associated with its regional connectivity.

    Directory of Open Access Journals (Sweden)

    Lior Wolf

    2011-05-01

    Full Text Available The putative link between gene expression of brain regions and their neural connectivity patterns is a fundamental question in neuroscience. Here this question is addressed in the first large scale study of a prototypical mammalian rodent brain, using a combination of rat brain regional connectivity data with gene expression of the mouse brain. Remarkably, even though this study uses data from two different rodent species (due to the data limitations, we still find that the connectivity of the majority of brain regions is highly predictable from their gene expression levels-the outgoing (incoming connectivity is successfully predicted for 73% (56% of brain regions, with an overall fairly marked accuracy level of 0.79 (0.83. Many genes are found to play a part in predicting both the incoming and outgoing connectivity (241 out of the 500 top selected genes, p-value<1e-5. Reassuringly, the genes previously known from the literature to be involved in axon guidance do carry significant information about regional brain connectivity. Surveying the genes known to be associated with the pathogenesis of several brain disorders, we find that those associated with schizophrenia, autism and attention deficit disorder are the most highly enriched in the connectivity-related genes identified here. Finally, we find that the profile of functional annotation groups that are associated with regional connectivity in the rodent is significantly correlated with the annotation profile of genes previously found to determine neural connectivity in C. elegans (Pearson correlation of 0.24, p<1e-6 for the outgoing connections and 0.27, p<1e-5 for the incoming. Overall, the association between connectivity and gene expression in a specific extant rodent species' brain is likely to be even stronger than found here, given the limitations of current data.

  11. Effects of physical exercise on central nervous system functions: a review of brain region specific adaptations.

    Science.gov (United States)

    Morgan, Julie A; Corrigan, Frances; Baune, Bernhard T

    2015-01-01

    Pathologies of central nervous system (CNS) functions are involved in prevalent conditions such as Alzheimer's disease, depression, and Parkinson's disease. Notable pathologies include dysfunctions of circadian rhythm, central metabolism, cardiovascular function, central stress responses, and movement mediated by the basal ganglia. Although evidence suggests exercise may benefit these conditions, the neurobiological mechanisms of exercise in specific brain regions involved in these important CNS functions have yet to be clarified. Here we review murine evidence about the effects of exercise on discrete brain regions involved in important CNS functions. Exercise effects on circadian rhythm, central metabolism, cardiovascular function, stress responses in the brain stem and hypothalamic pituitary axis, and movement are examined. The databases Pubmed, Web of Science, and Embase were searched for articles investigating regional brain adaptations to exercise. Brain regions examined included the brain stem, hypothalamus, and basal ganglia. We found evidence of multiple regional adaptations to both forced and voluntary exercise. Exercise can induce molecular adaptations in neuronal function in many instances. Taken together, these findings suggest that the regional physiological adaptations that occur with exercise could constitute a promising field for elucidating molecular and cellular mechanisms of recovery in psychiatric and neurological health conditions.

  12. Neurofilament protein defines regional patterns of cortical organization in the macaque monkey visual system: a quantitative immunohistochemical analysis

    Science.gov (United States)

    Hof, P. R.; Morrison, J. H.; Bloom, F. E. (Principal Investigator)

    1995-01-01

    Visual function in monkeys is subserved at the cortical level by a large number of areas defined by their specific physiological properties and connectivity patterns. For most of these cortical fields, a precise index of their degree of anatomical specialization has not yet been defined, although many regional patterns have been described using Nissl or myelin stains. In the present study, an attempt has been made to elucidate the regional characteristics, and to varying degrees boundaries, of several visual cortical areas in the macaque monkey using an antibody to neurofilament protein (SMI32). This antibody labels a subset of pyramidal neurons with highly specific regional and laminar distribution patterns in the cerebral cortex. Based on the staining patterns and regional quantitative analysis, as many as 28 cortical fields were reliably identified. Each field had a homogeneous distribution of labeled neurons, except area V1, where increases in layer IVB cell and in Meynert cell counts paralleled the increase in the degree of eccentricity in the visual field representation. Within the occipitotemporal pathway, areas V3 and V4 and fields in the inferior temporal cortex were characterized by a distinct population of neurofilament-rich neurons in layers II-IIIa, whereas areas located in the parietal cortex and part of the occipitoparietal pathway had a consistent population of large labeled neurons in layer Va. The mediotemporal areas MT and MST displayed a distinct population of densely labeled neurons in layer VI. Quantitative analysis of the laminar distribution of the labeled neurons demonstrated that the visual cortical areas could be grouped in four hierarchical levels based on the ratio of neuron counts between infragranular and supragranular layers, with the first (areas V1, V2, V3, and V3A) and third (temporal and parietal regions) levels characterized by low ratios and the second (areas MT, MST, and V4) and fourth (frontal regions) levels characterized by

  13. Neurofilament protein defines regional patterns of cortical organization in the macaque monkey visual system: a quantitative immunohistochemical analysis

    Science.gov (United States)

    Hof, P. R.; Morrison, J. H.; Bloom, F. E. (Principal Investigator)

    1995-01-01

    Visual function in monkeys is subserved at the cortical level by a large number of areas defined by their specific physiological properties and connectivity patterns. For most of these cortical fields, a precise index of their degree of anatomical specialization has not yet been defined, although many regional patterns have been described using Nissl or myelin stains. In the present study, an attempt has been made to elucidate the regional characteristics, and to varying degrees boundaries, of several visual cortical areas in the macaque monkey using an antibody to neurofilament protein (SMI32). This antibody labels a subset of pyramidal neurons with highly specific regional and laminar distribution patterns in the cerebral cortex. Based on the staining patterns and regional quantitative analysis, as many as 28 cortical fields were reliably identified. Each field had a homogeneous distribution of labeled neurons, except area V1, where increases in layer IVB cell and in Meynert cell counts paralleled the increase in the degree of eccentricity in the visual field representation. Within the occipitotemporal pathway, areas V3 and V4 and fields in the inferior temporal cortex were characterized by a distinct population of neurofilament-rich neurons in layers II-IIIa, whereas areas located in the parietal cortex and part of the occipitoparietal pathway had a consistent population of large labeled neurons in layer Va. The mediotemporal areas MT and MST displayed a distinct population of densely labeled neurons in layer VI. Quantitative analysis of the laminar distribution of the labeled neurons demonstrated that the visual cortical areas could be grouped in four hierarchical levels based on the ratio of neuron counts between infragranular and supragranular layers, with the first (areas V1, V2, V3, and V3A) and third (temporal and parietal regions) levels characterized by low ratios and the second (areas MT, MST, and V4) and fourth (frontal regions) levels characterized by

  14. Defining environmental flows requirements at regional scale by using meso-scale habitat models and catchments classification

    Science.gov (United States)

    Vezza, Paolo; Comoglio, Claudio; Rosso, Maurizio

    2010-05-01

    The alterations of the natural flow regime and in-stream channel modification due to abstraction from watercourses act on biota through an hydraulic template, which is mediated by channel morphology. Modeling channel hydro-morphology is needed in order to evaluate how much habitat is available for selected fauna under specific environmental conditions, and consequently to assist decision makers in planning options for regulated river management. Meso-scale habitat modeling methods (e.g., MesoHABSIM) offer advantages over the traditional physical habitat evaluation, involving a larger range of habitat variables, allowing longer length of surveyed rivers and enabling understanding of fish behavior at larger spatial scale. In this study we defined a bottom-up method for the ecological discharge evaluation at regional scale, focusing on catchments smaller than 50 km2, most of them located within mountainous areas of Apennines and Alps mountain range in Piedmont (NW Italy). Within the regional study domain we identified 30 representative catchments not affected by water abstractions in order to build up the habitat-flow relationship, to be used as reference when evaluating regulated watercourses or new projects. For each stream we chose a representative reach and obtained fish data by sampling every single functional habitat (i.e. meso-habitat) within the site, keeping separated each area by using nets. The target species were brown trout (Salmo trutta), marble trout (Salmo trutta marmoratus), bullhead (Cottus gobius), chub (Leuciscus cephalus), barbel (Barbus barbus), vairone (Leuciscus souffia) and other rheophilic Cyprinids. The fish habitat suitability criteria was obtained from the observation of habitat use by a selected organism described with a multivariate relationship between habitat characteristics and fish presence. Habitat type, mean slope, cover, biotic choriotop and substrate, stream depth and velocity, water pH, temperature and percentage of dissolved

  15. Gene expression in the rodent brain is associated with its regional connectivity.

    Science.gov (United States)

    Wolf, Lior; Goldberg, Chen; Manor, Nathan; Sharan, Roded; Ruppin, Eytan

    2011-05-01

    The putative link between gene expression of brain regions and their neural connectivity patterns is a fundamental question in neuroscience. Here this question is addressed in the first large scale study of a prototypical mammalian rodent brain, using a combination of rat brain regional connectivity data with gene expression of the mouse brain. Remarkably, even though this study uses data from two different rodent species (due to the data limitations), we still find that the connectivity of the majority of brain regions is highly predictable from their gene expression levels-the outgoing (incoming) connectivity is successfully predicted for 73% (56%) of brain regions, with an overall fairly marked accuracy level of 0.79 (0.83). Many genes are found to play a part in predicting both the incoming and outgoing connectivity (241 out of the 500 top selected genes, p-valueregional connectivity in the rodent is significantly correlated with the annotation profile of genes previously found to determine neural connectivity in C. elegans (Pearson correlation of 0.24, p<1e-6 for the outgoing connections and 0.27, p<1e-5 for the incoming). Overall, the association between connectivity and gene expression in a specific extant rodent species' brain is likely to be even stronger than found here, given the limitations of current data.

  16. Directional connectivity between frontal and posterior brain regions is altered with increasing concentrations of propofol.

    Science.gov (United States)

    Maksimow, Anu; Silfverhuth, Minna; Långsjö, Jaakko; Kaskinoro, Kimmo; Georgiadis, Stefanos; Jääskeläinen, Satu; Scheinin, Harry

    2014-01-01

    Recent studies using electroencephalography (EEG) suggest that alteration of coherent activity between the anterior and posterior brain regions might be used as a neurophysiologic correlate of anesthetic-induced unconsciousness. One way to assess causal relationships between brain regions is given by renormalized partial directed coherence (rPDC). Importantly, directional connectivity is evaluated in the frequency domain by taking into account the whole multichannel EEG, as opposed to time domain or two channel approaches. rPDC was applied here in order to investigate propofol induced changes in causal connectivity between four states of consciousness: awake (AWA), deep sedation (SED), loss (LOC) and return of consciousness (ROC) by gathering full 10/20 system human EEG data in ten healthy male subjects. The target-controlled drug infusion was started at low rate with subsequent gradual stepwise increases at 10 min intervals in order to carefully approach LOC (defined as loss of motor responsiveness to a verbal stimulus). The direction of the causal EEG-network connections clearly changed from AWA to SED and LOC. Propofol induced a decrease (p = 0.002-0.004) in occipital-to-frontal rPDC of 8-16 Hz EEG activity and an increase (p = 0.001-0.040) in frontal-to-occipital rPDC of 10-20 Hz activity on both sides of the brain during SED and LOC. In addition, frontal-to-parietal rPDC within 1-12 Hz increased in the left hemisphere at LOC compared to AWA (p = 0.003). However, no significant changes were detected between the SED and the LOC states. The observed decrease in back-to-front EEG connectivity appears compatible with impaired information flow from the posterior sensory and association cortices to the executive prefrontal areas, possibly related to decreased ability to perceive the surrounding world during sedation. The observed increase in the opposite (front-to-back) connectivity suggests a propofol concentration dependent association and is not directly related

  17. Directional connectivity between frontal and posterior brain regions is altered with increasing concentrations of propofol.

    Directory of Open Access Journals (Sweden)

    Anu Maksimow

    Full Text Available Recent studies using electroencephalography (EEG suggest that alteration of coherent activity between the anterior and posterior brain regions might be used as a neurophysiologic correlate of anesthetic-induced unconsciousness. One way to assess causal relationships between brain regions is given by renormalized partial directed coherence (rPDC. Importantly, directional connectivity is evaluated in the frequency domain by taking into account the whole multichannel EEG, as opposed to time domain or two channel approaches. rPDC was applied here in order to investigate propofol induced changes in causal connectivity between four states of consciousness: awake (AWA, deep sedation (SED, loss (LOC and return of consciousness (ROC by gathering full 10/20 system human EEG data in ten healthy male subjects. The target-controlled drug infusion was started at low rate with subsequent gradual stepwise increases at 10 min intervals in order to carefully approach LOC (defined as loss of motor responsiveness to a verbal stimulus. The direction of the causal EEG-network connections clearly changed from AWA to SED and LOC. Propofol induced a decrease (p = 0.002-0.004 in occipital-to-frontal rPDC of 8-16 Hz EEG activity and an increase (p = 0.001-0.040 in frontal-to-occipital rPDC of 10-20 Hz activity on both sides of the brain during SED and LOC. In addition, frontal-to-parietal rPDC within 1-12 Hz increased in the left hemisphere at LOC compared to AWA (p = 0.003. However, no significant changes were detected between the SED and the LOC states. The observed decrease in back-to-front EEG connectivity appears compatible with impaired information flow from the posterior sensory and association cortices to the executive prefrontal areas, possibly related to decreased ability to perceive the surrounding world during sedation. The observed increase in the opposite (front-to-back connectivity suggests a propofol concentration dependent association and is not directly

  18. The role of cancer stem cells and miRNAs in defining the complexities of brain metastasis

    OpenAIRE

    2013-01-01

    Researchers and clinicians have been challenged with the development of therapies for the treatment of cancer patients whose tumors metastasized to the brain. Among the most lethal weapons known today, current management of brain metastases involves multiple therapeutic modalities that provide little, if any, for improving the quality of life and overall survival. Recently the role of cancer stem cells (CSCs) in the development of cancer has been studied extensively, and thus its role in the ...

  19. Hormone replacement therapy and age-related brain shrinkage: regional effects.

    Science.gov (United States)

    Raz, Naftali; Rodrigue, Karen M; Kennedy, Kristen M; Acker, James D

    2004-11-15

    Neuroprotective properties of estrogen have been established in animal models, but clinical trials of hormone replacement therapy (HRT) produced contradictory results. We examined the impact of HRT on age-related regional changes in human brain volume. Six brain regions were measured twice, five years apart, in 12 healthy women who took HRT and in matched controls who did not. The controls showed a typical pattern of differential brain shrinkage in the association cortices and the hippocampus with no change in the primary visual cortex. In contrast, women who took HRT showed comparable shrinkage of the hippocampus but no significant shrinkage of the neocortex. Future large scale studies may benefit from applying regional rather than global measures in assessment of brain integrity.

  20. Response of regional brain glutamate transaminases of rat to aluminum in protein malnutrition

    Science.gov (United States)

    Nayak, Prasunpriya; Chatterjee, Ajay K

    2002-01-01

    Background The mechanism of aluminum-induced neurotoxicity is not clear. The involvement of glutamate in the aluminium-induced neurocomplications has been suggested. Brain glutamate levels also found to be altered in protein malnutrition. Alterations in glutamate levels as well as glutamate-α-decarboxylase in different regions of rat brain has been reported in response to aluminum exposure. Thus the study of glutamate metabolising enzymes in different brain regions of rats maintained on either normal or restricted protein diet may be of importance for understanding the neurotoxicity properties of aluminium. Results Dietary protein restrictions does not have an significant impact on regional aluminum content of the brain. The interaction of aluminum intoxication and protein restriction is significant in the thalamic area and the midbrain-hippocampal region in cases of glutamate oxaloacetate transaminase. In the case of gluatmate pyruvate transaminase, this interaction is significant only in thalamic area. Conclusion The metabolism of amino acids, as indicated by activities of specific transaminases, of brain is altered in response to aluminum exposure. These alterations are region specific and are dependent on dietary protein intake or manipulation of the brain amino acid homeostasis. PMID:12197946

  1. Response of regional brain glutamate transaminases of rat to aluminum in protein malnutrition

    Directory of Open Access Journals (Sweden)

    Chatterjee Ajay K

    2002-08-01

    Full Text Available Abstract Background The mechanism of aluminum-induced neurotoxicity is not clear. The involvement of glutamate in the aluminium-induced neurocomplications has been suggested. Brain glutamate levels also found to be altered in protein malnutrition. Alterations in glutamate levels as well as glutamate-α-decarboxylase in different regions of rat brain has been reported in response to aluminum exposure. Thus the study of glutamate metabolising enzymes in different brain regions of rats maintained on either normal or restricted protein diet may be of importance for understanding the neurotoxicity properties of aluminium. Results Dietary protein restrictions does not have an significant impact on regional aluminum content of the brain. The interaction of aluminum intoxication and protein restriction is significant in the thalamic area and the midbrain-hippocampal region in cases of glutamate oxaloacetate transaminase. In the case of gluatmate pyruvate transaminase, this interaction is significant only in thalamic area. Conclusion The metabolism of amino acids, as indicated by activities of specific transaminases, of brain is altered in response to aluminum exposure. These alterations are region specific and are dependent on dietary protein intake or manipulation of the brain amino acid homeostasis.

  2. 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

    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...... 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...

  3. Development of regional cerebral oedema after lateral fluid-percussion brain injury in the rat.

    Science.gov (United States)

    McIntosh, T K; Soares, H; Thomas, M; Cloherty, K

    1990-01-01

    Most studies attempting to characterize post-traumatic oedema formation have focused on the acute postinjury period. We have recently developed a new model of lateral (parasagittal) fluidpercussion (FP) brain injury in the rat. The purpose of the present study was to characterize the temporal course of oedema formation and resolution in this experimental model of brain injury. Male Sprague-Dawley rats (n = 67) were anaesthetized and subjected to FP brain injury of moderate severity. Animals were sacrified at 1 hour, 6 hours, 24 hours, 2 days, 3 days, 5 days and 7 days after brain injury, brains removed and assayed for water content using either specific gravitimetric or wet weight/dry weight techniques. In the injured left parietal cortex, a significant increase in water content was observed by 6 hours postinjury (p less than 0.05) that persisted up to 5 days postinjury. A prolonged and significant increase in water content was also observed in the left (ipsilateral) hippocampus which began at 1 hour postinjury (p less than 0.05) and continued up to 3 days. Other regions examined showed no significant regional oedema after brain injury. These results suggest that lateral FP brain injury produces an early focus oedema that persists for a prolonged period after trauma. This model may be useful in the evaluation of novel pharmacological therapies designed to reduce cerebral oedema after brain injury.

  4. 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.

  5. The DNA methylome and transcriptome of different brain regions in schizophrenia and bipolar disorder.

    Directory of Open Access Journals (Sweden)

    Yun Xiao

    Full Text Available Extensive changes in DNA methylation have been observed in schizophrenia (SC and bipolar disorder (BP, and may contribute to the pathogenesis of these disorders. Here, we performed genome-scale DNA methylation profiling using methylated DNA immunoprecipitation followed by sequencing (MeDIP-seq on two brain regions (including frontal cortex and anterior cingulate in 5 SC, 7 BP and 6 normal subjects. Comparing with normal controls, we identified substantial differentially methylated regions (DMRs in these two brain regions of SC and BP. To our surprise, different brain regions show completely distinct distributions of DMRs across the genomes. In frontal cortex of both SC and BP subjects, we observed widespread hypomethylation as compared to normal controls, preferentially targeting the terminal ends of the chromosomes. In contrast, in anterior cingulate, both SC and BP subjects displayed extensive gain of methylation. Notably, in these two brain regions of SC and BP, only a few DMRs overlapped with promoters, whereas a greater proportion occurs in introns and intergenic regions. Functional enrichment analysis indicated that important psychiatric disorder-related biological processes such as neuron development, differentiation and projection may be altered by epigenetic changes located in the intronic regions. Transcriptome analysis revealed consistent dysfunctional processes with those determined by DMRs. Furthermore, DMRs in the same brain regions from SC and BP could successfully distinguish BP and/or SC from normal controls while differentially expressed genes could not. Overall, our results support a major role for brain-region-dependent aberrant DNA methylation in the pathogenesis of these two disorders.

  6. Distinct α-intercalated cell morphology and its modification by acidosis define regions of the collecting duct

    Science.gov (United States)

    Purkerson, Jeffrey M.; Schwaderer, Andrew L.; Nakamori, Aya

    2015-01-01

    During metabolic acidosis, the cortical collecting duct (CCD) of the rabbit reverses the polarity of bicarbonate flux from net secretion to net absorption, and this is accomplished by increasing the proton secretory rate by α-intercalated cells (ICs) and decreasing bicarbonate secretion by β-ICs. To better characterize dynamic changes in H+-secreting α-ICs, we examined their morphology in collecting ducts microdissected from kidneys of normal, acidotic, and recovering rabbits. α-ICs in defined axial regions varied in number and basolateral anion exchanger (AE)1 morphology, which likely reflects their relative activity and function along the collecting duct. Upon transition from CCD to outer medullary collecting duct from the outer stripe to the inner stripe, the number of α-ICs increases from 11.0 ± 1.2 to 15.4 ± 1.11 and to 32.0 ± 1.3 cells/200 μm, respectively. In the CCD, the basolateral structure defined by AE1 typically exhibited a pyramidal or conical shape, whereas in the medulla the morphology was elongated and shallow, resulting in a more rectangular shape. Furthermore, acidosis reversibly induced α-ICs in the CCD to acquire a more rectangular morphology concomitant with a transition from diffusely cytoplasmic to increased basolateral surface distribution of AE1 and apical polarization of B1-V-ATPase. The latter results are consistent with the supposition that morphological adaptation from the pyramidal to rectangular shape reflects a transition toward a more “active” configuration. In addition, α-ICs in the outer medullary collecting duct from the outer stripe exhibited cellular morphology strikingly similar to dendritic cells that may reflect a newly defined ancillary function in immune defense of the kidney. PMID:26084929

  7. 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.

  8. Test-retest reproducibility for regional brain metabolic responses to lorazepam

    Energy Technology Data Exchange (ETDEWEB)

    Wang, G.J.; Volkow, N.D.; Overall, J. [Brookhaven National Lab., Upton, NY (United States)]|[SUNY, Stony Brook, NY (United States)]|[Univ. of Texas, Houston, TX (United States)]|[VAMC, Northport, NY (United States)] [and others

    1996-05-01

    Changes in regional brain glucose metabolism as assessed with PET and FDG in response to acute administration of benzodiazepine agonists have been used as indicators of benzodiazepine-GABA receptor function. The purpose of this study was to assess the reproducibility of these responses. Sixteen healthy right-handed men were scanned with positron emission tomography (PET) and [F-18] fluorodeoxyglucose (FDG) twice: prior to placebo and prior to lorazepam (30 {mu}g/kg). The same double FDG procedure was repeated 6-8 weeks later to assess test-retest reproducibility. The regional absolute brain metabolic values obtained during the second evaluation were significantly lower than those obtained for the first evaluation regardless of condition (p {le} 0.001). Lorazepam significantly and consistently decreased whole brain metabolism and the magnitude as well as the regional pattern of the changes was comparable for both studies (12.3 {plus_minus} 6.9% and 13.7 {plus_minus} 7.4%). Lorazepam effects were largest in thalamus (22.2 {plus_minus} 8.9%). Relative metabolic measures ROI/global were highly reproducible both for drug as well as replication condition. This is the first study to measure test-retest reproducibility in regional brain metabolic response to a pharmacological challenge. While the global and regional absolute metabolic values were significantly lower for the repeated evaluation, the regional brain metabolic response to lorazepam was highly reproducible.

  9. Brain region-specificity of palmitic acid-induced abnormalities associated with Alzheimer's disease

    Directory of Open Access Journals (Sweden)

    Melrose Joseph

    2008-06-01

    Full Text Available Abstract Background Alzheimer's disease (AD is a progressive, neurodegenerative disease mostly affecting the basal forebrain, cortex and hippocampus whereas the cerebellum is relatively spared. The reason behind this region-specific brain damage in AD is not well understood. Here, we report our data suggesting "differential free fatty acid metabolism in the different brain areas" as a potentially important factor in causing the region-specific damage observed in AD brain. Findings The astroglia from two different rat brain regions, cortex (region affected in AD and cerebellum (unaffected region, were treated with 0.2 mM of palmitic acid. The conditioned media were then transferred to the cortical neurons to study the possible effects on the two main, AD-associated protein abnormalities, viz. BACE1 upregulation and hyperphosphorylation of tau. The conditioned media from palmitic-acid treated cortical astroglia, but not the cerebellar astroglia, significantly elevated levels of phosphorylated tau and BACE1 in cortical neurons as compared to controls (47 ± 7% and 45 ± 4%, respectively. Conclusion The present data provide an experimental explanation for the region-specific damage observed in AD brain; higher fatty acid-metabolizing capacity of cortical astroglia as compared to cerebellar astroglia, may play a causal role in increasing vulnerability of cortex in AD, while sparing cerebellum.

  10. Dual role of cerebral blood flow in regional brain temperature control in the healthy newborn infant.

    Science.gov (United States)

    Iwata, Sachiko; Tachtsidis, Ilias; Takashima, Sachio; Matsuishi, Toyojiro; Robertson, Nicola J; Iwata, Osuke

    2014-10-01

    Small shifts in brain temperature after hypoxia-ischaemia affect cell viability. The main determinants of brain temperature are cerebral metabolism, which contributes to local heat production, and brain perfusion, which removes heat. However, few studies have addressed the effect of cerebral metabolism and perfusion on regional brain temperature in human neonates because of the lack of non-invasive cot-side monitors. This study aimed (i) to determine non-invasive monitoring tools of cerebral metabolism and perfusion by combining near-infrared spectroscopy and echocardiography, and (ii) to investigate the dependence of brain temperature on cerebral metabolism and perfusion in unsedated newborn infants. Thirty-two healthy newborn infants were recruited. They were studied with cerebral near-infrared spectroscopy, echocardiography, and a zero-heat flux tissue thermometer. A surrogate of cerebral blood flow (CBF) was measured using superior vena cava flow adjusted for cerebral volume (rSVC flow). The tissue oxygenation index, fractional oxygen extraction (FOE), and the cerebral metabolic rate of oxygen relative to rSVC flow (CMRO₂ index) were also estimated. A greater rSVC flow was positively associated with higher brain temperatures, particularly for superficial structures. The CMRO₂ index and rSVC flow were positively coupled. However, brain temperature was independent of FOE and the CMRO₂ index. A cooler ambient temperature was associated with a greater temperature gradient between the scalp surface and the body core. Cerebral oxygen metabolism and perfusion were monitored in newborn infants without using tracers. In these healthy newborn infants, cerebral perfusion and ambient temperature were significant independent variables of brain temperature. CBF has primarily been associated with heat removal from the brain. However, our results suggest that CBF is likely to deliver heat specifically to the superficial brain. Further studies are required to assess the

  11. Decreased Functional Connectivity of Homotopic Brain Regions in Chronic Stroke Patients: A Resting State fMRI Study

    Science.gov (United States)

    Chen, Chuang; Zheng, Xiaohui; Sun, Fenfen; Zhang, Xiaoli; Tian, Jing; Fan, Mingxia; Wu, Yi; Jia, Jie

    2016-01-01

    The recovery of motor functions is accompanied by brain reorganization, and identifying the inter-hemispheric interaction post stroke will conduce to more targeted treatments. However, the alterations of bi-hemispheric coordination pattern between homologous areas in the whole brain for chronic stroke patients were still unclear. The present study focuses on the functional connectivity (FC) of mirror regions of the whole brain to investigate the inter-hemispheric interaction using a new fMRI method named voxel-mirrored homotopic connectivity (VMHC). Thirty left subcortical chronic stroke patients with pure motor deficits and 37 well-matched healthy controls (HCs) underwent resting-state fMRI scans. We employed a VMHC analysis to determine the brain areas showed significant differences between groups in FC between homologous regions, and we explored the relationships between the mean VMHC of each survived area and clinical tests within patient group using Pearson correlation. In addition, the brain areas showed significant correlations between the mean VMHC and clinical tests were defined as the seed regions for whole brain FC analysis. Relative to HCs, patients group displayed lower VMHC in the precentral gyrus, postcentral gyrus, inferior frontal gyrus, middle temporal gyrus, calcarine gyrus, thalamus, cerebellum anterior lobe, and cerebellum posterior lobe (CPL). Moreover, the VMHC of CPL was positively correlated with the Fugl–Meyer Score of hand (FMA-H), while a negative correlation between illness duration and the VMHC of this region was also detected. Furthermore, we found that when compared with HCs, the right CPL exhibited reduced FC with the left precentral gyrus, inferior frontal gyrus, inferior parietal lobule, middle temporal gyrus, thalamus and hippocampus. Our results suggest that the functional coordination across hemispheres is impaired in chronic stroke patients, and increased VMHC of the CPL is significantly associated with higher FMA-H scores

  12. 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

  13. Investment in higher order central processing regions is not constrained by brain size in social insects.

    Science.gov (United States)

    Muscedere, Mario L; Gronenberg, Wulfila; Moreau, Corrie S; Traniello, James F A

    2014-06-07

    The extent to which size constrains the evolution of brain organization and the genesis of complex behaviour is a central, unanswered question in evolutionary neuroscience. Advanced cognition has long been linked to the expansion of specific brain compartments, such as the neocortex in vertebrates and the mushroom bodies in insects. Scaling constraints that limit the size of these brain regions in small animals may therefore be particularly significant to behavioural evolution. Recent findings from studies of paper wasps suggest miniaturization constrains the size of central sensory processing brain centres (mushroom body calyces) in favour of peripheral, sensory input centres (antennal and optic lobes). We tested the generality of this hypothesis in diverse eusocial hymenopteran species (ants, bees and wasps) exhibiting striking variation in body size and thus brain size. Combining multiple neuroanatomical datasets from these three taxa, we found no universal size constraint on brain organization within or among species. In fact, small-bodied ants with miniscule brains had mushroom body calyces proportionally as large as or larger than those of wasps and bees with brains orders of magnitude larger. Our comparative analyses suggest that brain organization in ants is shaped more by natural selection imposed by visual demands than intrinsic design limitations.

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

    Directory of Open Access Journals (Sweden)

    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.

  15. Macro-to-micro cortical vascular imaging underlies regional differences in ischemic brain.

    Science.gov (United States)

    Dziennis, Suzan; Qin, Jia; Shi, Lei; Wang, Ruikang K

    2015-05-05

    The ability to non-invasively monitor and quantify hemodynamic responses down to the capillary level is important for improved diagnosis, treatment and management of neurovascular disorders, including stroke. We developed an integrated multi-functional imaging system, in which synchronized dual wavelength laser speckle contrast imaging (DWLS) was used as a guiding tool for optical microangiography (OMAG) to test whether detailed vascular responses to experimental stroke in male mice can be evaluated with wide range sensitivity from arteries and veins down to the capillary level. DWLS enabled rapid identification of cerebral blood flow (CBF), prediction of infarct area and hemoglobin oxygenation over the whole mouse brain and was used to guide the OMAG system to hone in on depth information regarding blood volume, blood flow velocity and direction, vascular architecture, vessel diameter and capillary density pertaining to defined regions of CBF in response to ischemia. OMAG-DWLS is a novel imaging platform technology to simultaneously evaluate multiple vascular responses to ischemic injury, which can be useful in improving our understanding of vascular responses under pathologic and physiological conditions, and ultimately facilitating clinical diagnosis, monitoring and therapeutic interventions of neurovascular diseases.

  16. Macro-to-micro cortical vascular imaging underlies regional differences in ischemic brain

    Science.gov (United States)

    Dziennis, Suzan; Qin, Jia; Shi, Lei; Wang, Ruikang K.

    2015-05-01

    The ability to non-invasively monitor and quantify hemodynamic responses down to the capillary level is important for improved diagnosis, treatment and management of neurovascular disorders, including stroke. We developed an integrated multi-functional imaging system, in which synchronized dual wavelength laser speckle contrast imaging (DWLS) was used as a guiding tool for optical microangiography (OMAG) to test whether detailed vascular responses to experimental stroke in male mice can be evaluated with wide range sensitivity from arteries and veins down to the capillary level. DWLS enabled rapid identification of cerebral blood flow (CBF), prediction of infarct area and hemoglobin oxygenation over the whole mouse brain and was used to guide the OMAG system to hone in on depth information regarding blood volume, blood flow velocity and direction, vascular architecture, vessel diameter and capillary density pertaining to defined regions of CBF in response to ischemia. OMAG-DWLS is a novel imaging platform technology to simultaneously evaluate multiple vascular responses to ischemic injury, which can be useful in improving our understanding of vascular responses under pathologic and physiological conditions, and ultimately facilitating clinical diagnosis, monitoring and therapeutic interventions of neurovascular diseases.

  17. Deletions of a differentially methylated CpG island at SNRPN define a putative imprinting control region

    Energy Technology Data Exchange (ETDEWEB)

    Sutcliffe, J.S.,; Nakao, M.; Beaudet, A.L. [Baylor College of Medicine, Houston, TX (United States)] [and others

    1994-09-01

    Prader-Willi syndrome (PWS) and Angelman syndrome (AS) are associated with paternal and maternal deficiencies, respectively, of gene expression within human chromosome 15q11-q13, and are caused by deletion, uniparental disomy, or other mutations. Four transcripts designated PAR-5, PAR-7, PAR-1 and PAR-4 were isolated and localized to a region within 300 kb telomeric to the gene encoding small nuclear ribonucleoprotein-associated polypeptide N (SNRPN). Analysis of the transcripts in cultured fibroblasts and lymphoblasts from deletion patients demonstrated that SNRPN, PAR-5 and PAR-1 are expressed exclusively from the paternal chromosome, defining an imprinted domain that spans at least 200 kb. All three imprinted transcripts were absent in cells from three PWS patients (one pair of sibs and one sporadic case) with small deletions that involve a differentially methylated CpG island containing a previously undescribed 5{prime} untranslated exon ({alpha}) of SNRPN. Methylation of the CpG island is specific for the maternal chromosome consistent with paternal expression of the imprinted domain. One deletion, which is benign when maternally transmitted, extends upstream <30 kb from the CpG island, and is associated with altered methylation centromeric to SNRPN, and loss of transcription telomeric to SNRPN, implying the presence of an imprinting control region around the CpG island containing exon {alpha}.

  18. Brain regions associated with visual cues are important for bird migration.

    Science.gov (United States)

    Vincze, Orsolya; Vágási, Csongor I; Pap, Péter L; Osváth, Gergely; Møller, Anders Pape

    2015-11-01

    Long-distance migratory birds have relatively smaller brains than short-distance migrants or residents. Here, we test whether reduction in brain size with migration distance can be generalized across the different brain regions suggested to play key roles in orientation during migration. Based on 152 bird species, belonging to 61 avian families from six continents, we show that the sizes of both the telencephalon and the whole brain decrease, and the relative size of the optic lobe increases, while cerebellum size does not change with increasing migration distance. Body mass, whole brain size, optic lobe size and wing aspect ratio together account for a remarkable 46% of interspecific variation in average migration distance across bird species. These results indicate that visual acuity might be a primary neural adaptation to the ecological challenge of migration. © 2015 The Author(s).

  19. Efficient regeneration by activation of neurogenesis in homeostatically quiescent regions of the adult vertebrate brain.

    Science.gov (United States)

    Berg, Daniel A; Kirkham, Matthew; Beljajeva, Anna; Knapp, Dunja; Habermann, Bianca; Ryge, Jesper; Tanaka, Elly M; Simon, András

    2010-12-01

    In contrast to mammals, salamanders and teleost fishes can efficiently repair the adult brain. It has been hypothesised that constitutively active neurogenic niches are a prerequisite for extensive neuronal regeneration capacity. Here, we show that the highly regenerative salamander, the red spotted newt, displays an unexpectedly similar distribution of active germinal niches with mammals under normal physiological conditions. Proliferation zones in the adult newt brain are restricted to the forebrain, whereas all other regions are essentially quiescent. However, ablation of midbrain dopamine neurons in newts induced ependymoglia cells in the normally quiescent midbrain to proliferate and to undertake full dopamine neuron regeneration. Using oligonucleotide microarrays, we have catalogued a set of differentially expressed genes in these activated ependymoglia cells. This strategy identified hedgehog signalling as a key component of adult dopamine neuron regeneration. These data show that brain regeneration can occur by activation of neurogenesis in quiescent brain regions.

  20. Brain Region and Cell Type Transcripts for Informative Diagnostics

    Science.gov (United States)

    2010-09-01

    to 8, the caudoputamen (CP), Globus pallidus internal and external segment (GPi, GPe), inner cerebral cortex (CTX), piriform cortex (PIR), corpus...Hippocampus Formation), PIR ( piriform cortex), and TH (Thalamus). More specifically, the VS region is usually increased with age and enlarged in a number of

  1. Defining Face Perception Areas in the Human Brain: A Large-Scale Factorial fMRI Face Localizer Analysis

    Science.gov (United States)

    Rossion, Bruno; Hanseeuw, Bernard; Dricot, Laurence

    2012-01-01

    A number of human brain areas showing a larger response to faces than to objects from different categories, or to scrambled faces, have been identified in neuroimaging studies. Depending on the statistical criteria used, the set of areas can be overextended or minimized, both at the local (size of areas) and global (number of areas) levels. Here…

  2. Defining Face Perception Areas in the Human Brain: A Large-Scale Factorial fMRI Face Localizer Analysis

    Science.gov (United States)

    Rossion, Bruno; Hanseeuw, Bernard; Dricot, Laurence

    2012-01-01

    A number of human brain areas showing a larger response to faces than to objects from different categories, or to scrambled faces, have been identified in neuroimaging studies. Depending on the statistical criteria used, the set of areas can be overextended or minimized, both at the local (size of areas) and global (number of areas) levels. Here…

  3. Global and regional cortical connectivity maturation index (CCMI) of developmental human brain with quantification of short-range association tracts

    Science.gov (United States)

    Ouyang, Minhui; Jeon, Tina; Mishra, Virendra; Du, Haixiao; Wang, Yu; Peng, Yun; Huang, Hao

    2016-03-01

    From early childhood to adulthood, synaptogenesis and synaptic pruning continuously reshape the structural architecture and neural connection in developmental human brains. Disturbance of the precisely balanced strengthening of certain axons and pruning of others may cause mental disorders such as autism and schizophrenia. To characterize this balance, we proposed a novel measurement based on cortical parcellation and diffusion MRI (dMRI) tractography, a cortical connectivity maturation index (CCMI). To evaluate the spatiotemporal sensitivity of CCMI as a potential biomarker, dMRI and T1 weighted datasets of 21 healthy subjects 2-25 years were acquired. Brain cortex was parcellated into 68 gyral labels using T1 weighted images, then transformed into dMRI space to serve as the seed region of interest for dMRI-based tractography. Cortico-cortical association fibers initiated from each gyrus were categorized into long- and short-range ones, based on the other end of fiber terminating in non-adjacent or adjacent gyri of the seed gyrus, respectively. The regional CCMI was defined as the ratio between number of short-range association tracts and that of all association tracts traced from one of 68 parcellated gyri. The developmental trajectory of the whole brain CCMI follows a quadratic model with initial decreases from 2 to 16 years followed by later increases after 16 years. Regional CCMI is heterogeneous among different cortical gyri with CCMI dropping to the lowest value earlier in primary somatosensory cortex and visual cortex while later in the prefrontal cortex. The proposed CCMI may serve as sensitive biomarker for brain development under normal or pathological conditions.

  4. Data for behavioral results and brain regions showing a time effect during pair-association retrieval

    Directory of Open Access Journals (Sweden)

    Koji Jimura

    2016-09-01

    Full Text Available The current data article provides behavioral and neuroimaging data for the research article "Relatedness-dependent rapid development of brain activity in anterior temporal cortex during pair-association retrieval” (Jimura et al., 2016 [1]. Behavioral performance is provided in a table. Fig. 2 of the article is based on this table. Brain regions showing time effect are provided in a table. A statistical activation map for the time effect is shown in Fig. 3C of the article.

  5. Brain regional differences in CB1 receptor adaptation and regulation of transcription

    OpenAIRE

    Lazenka, M.F.; Selley, D.E.; Sim-Selley, L J

    2012-01-01

    Cannabinoid CB1 receptors (CB1Rs) are expressed throughout the brain and mediate the central effects of cannabinoids, including Δ9-tetrahydrocannabinol (THC), the main psychoactive constituent of marijuana. Repeated THC administration produces tolerance to cannabinoid-mediated effects, although the magnitude of tolerance varies by effect. Consistent with this observation, CB1R desensitization and downregulation, as well induction of immediate early genes (IEGs), varies by brain region. Zif268...

  6. Effect of whole-brain irradiation on the specific brain regions in a rat model: Metabolic and histopathological changes.

    Science.gov (United States)

    Bálentová, Soňa; Hnilicová, Petra; Kalenská, Dagmar; Murín, Peter; Hajtmanová, Eva; Lehotský, Ján; Adamkov, Marian

    2017-05-01

    Effect of ionizing radiation on the brain affects neuronal, glial, and endothelial cell population and lead to significant morphological, metabolic, and functional deficits. In the present study we investigated a dose- and time-dependent correlation between radiation-induced metabolic and histopathological changes. Adult male Wistar rats received a total dose of 35Gy delivered in 7 fractions (dose 5Gy per fraction) once per week in the same weekday during 7 consecutive weeks. Proton magnetic resonance spectroscopy ((1)H MRS), histochemistry, immunohistochemistry and confocal microscopy were used to determine whether radiation-induced alteration of the brain metabolites correlates with appropriate histopathological changes of neurogenesis and glial cell response in 2 neurogenic regions: the hippocampal dentate gyrus (DG) and the subventricular zone-olfactory bulb axis (SVZ-OB axis). Evaluation of the brain metabolites 18-19 weeks after irradiation performed by (1)H MRS revealed a significant decrease in the total N-acetylaspartate to total creatine (tNAA/tCr) ratio in the striatum and OB. A significant decline of gamma-aminobutyric acid to tCr (GABA/tCr) ratio was seen in the OB and hippocampus. MR revealed absence of gross inflammatory or necrotic lesions in these regions. Image analysis of the brain sections 18-21 weeks after the exposure showed a radiation-induced increase of neurodegeneration, inhibition of neurogenesis and strong resemblance to the reactive astrogliosis. Results showed that fractionated whole-brain irradiation led to the changes in neurotransmission and to the loss of neuronal viability in vivo. Metabolic changes were closely associated with histopathological findings, i.e. initiation of neuronal cell death, inhibition of neurogenesis and strong response of astrocytes indicated development of late radiation-induced changes. Copyright © 2017 Elsevier B.V. All rights reserved.

  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. 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.

  9. 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.)

  10. Differential production of reactive oxygen species in distinct brain regions of hypoglycemic mice.

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    Amador-Alvarado, Leticia; Montiel, Teresa; Massieu, Lourdes

    2014-09-01

    Hypoglycemia is a serious complication of insulin therapy in patients suffering from type 1 Diabetes Mellitus. Severe hypoglycemia leading to coma (isoelectricity) induces massive neuronal death in vulnerable brain regions such as the hippocampus, the striatum and the cerebral cortex. It has been suggested that the production of reactive oxygen species (ROS) and oxidative stress is involved in hypoglycemic brain damage, and that ROS generation is stimulated by glucose reintroduction (GR) after the hypoglycemic coma. However, the distribution of ROS in discrete brain regions has not been studied in detail. Using the oxidation sensitive marker dihydroethidium (DHE) we have investigated the distribution of ROS in different regions of the mouse brain during prolonged severe hypoglycemia without isoelectricity, as well as the effect of GR on ROS levels. Results show that ROS generation increases in the hippocampus, the cerebral cortex and the striatum after prolonged severe hypoglycemia before the coma. The hippocampus showed the largest increases in ROS levels. GR further stimulated ROS production in the hippocampus and the striatum while in the cerebral cortex, only the somatosensory and parietal areas were significantly affected by GR. Results suggest that ROS are differentially produced during the hypoglycemic insult and that a different response to GR is present among distinct brain regions.

  11. 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.

  12. 60 YEARS OF NEUROENDOCRINOLOGY: Celebrating the brain's other output-input system and the monograph that defined neuroendocrinology.

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    Coen, Clive W

    2015-08-01

    The brain's unimaginably complex operations are expressed in just two types of output: muscle activity and hormone release. These are the means by which the brain acts beyond its bony casing. Muscle-mediated actions (such as speaking, writing, pupillary reflexes) send signals to the outside world that may convey thoughts, emotions or evidence of neurological disorder. The outputs of the brain as a hormone secreting gland are usually less evident. Their discovery required several paradigm shifts in our understanding of anatomy. The first occurred in 1655. Exactly 300 years later, Geoffrey Harris' monograph Neural control of the pituitary gland launched the scientific discipline that is now known as neuroendocrinology. His hypotheses have stood the test of time to a remarkable degree. A key part of his vision concerned the two-way 'interplay between the central nervous system and endocrine glands'. Over the past 60 years, the importance of this reciprocity and the degree to which cerebral functions are influenced by the endocrine environment have become increasingly clear. © 2015 Society for Endocrinology.

  13. MRI patterns of atrophy and hypoperfusion associations across brain regions in frontotemporal dementia.

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    Tosun, Duygu; Rosen, Howard; Miller, Bruce L; Weiner, Michael W; Schuff, Norbert

    2012-02-01

    Magnetic Resonance Imaging (MRI) provides various imaging modes to study the brain. We tested the benefits of a joint analysis of multimodality MRI data in combination with a large-scale analysis that involved simultaneously all image voxels using joint independent components analysis (jICA) and compared the outcome to results using conventional voxel-by-voxel unimodality tests. Specifically, we designed a jICA to decompose multimodality MRI data into independent components that explain joint variations between the image modalities as well as variations across brain regions. We tested the jICA design on structural and perfusion-weighted MRI data from 12 patients diagnosed with behavioral variant frontotemporal dementia (bvFTD) and 12 cognitively normal elderly individuals. While unimodality analyses showed widespread brain atrophy and hypoperfusion in the patients, jICA further revealed two significant joint components of variations between atrophy and hypoperfusion across brain regions. The 1st joint component revealed associated brain atrophy and hypoperfusion predominantly in the right brain hemisphere in behavioral variant frontotemporal dementia, and the 2nd joint component revealed greater atrophy relative to hypoperfusion affecting predominantly the left hemisphere in behavioral variant frontotemporal dementia. The patterns are consistent with the clinical symptoms of behavioral variant frontotemporal dementia that relate to asymmetric compromises of the left and right brain hemispheres. The joint components also revealed that that structural alterations can be associated with physiological alterations in spatially separated but potentially connected brain regions. Finally, jICA outperformed voxel-by-voxel unimodal tests significantly in terms of an effect size, separating the behavioral variant frontotemporal dementia patients from the controls. Taken together, the results demonstrate the benefit of multimodality MRI in conjunction with jICA for mapping

  14. 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

  15. Simian virus 40 regulatory region structural diversity and the association of viral archetypal regulatory regions with human brain tumors.

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    Lednicky, J A; Butel, J S

    2001-02-01

    The regulatory region (RR) of simian virus 40 (SV40) contains enhancer/promoter elements and an origin of DNA replication. Natural SV40 isolates from simian brain or kidney tissues typically have an archetypal RR arrangement with a single 72-basepair enhancer element. A rare simpler, shorter SV40 RR exists that lacks a duplicated sequence in the G/C-rich region and is termed protoarchetypal. Occasionally, SV40 strain variants arise de novo that have complex RRs, which typically contain sequence reiterations, rearrangements, and/or deletions. These variants replicate faster and to higher titers in tissue culture; we speculate that such faster-growing variants were selected when laboratory strains of SV40 were initially recovered. SV40 strains with archetypal RRs have been found in some human brain tumors. The possible implications of these findings and a brief review of the SV40 RR structure are presented.

  16. Aberrant Global and Regional Topological Organization of the Fractional Anisotropy-weighted Brain Structural Networks in Major Depressive Disorder

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    Jian-Huai Chen

    2016-01-01

    Conclusions: All these resulted in a less optimal topological organization of networks underlying MDD patients, including an impaired capability of local information processing, reduced centrality of some brain regions and limited capacity to integrate information across different regions. Thus, these global network and regional node-level aberrations might contribute to understanding the pathogenesis of MDD from the view of the brain network.

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

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    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

  18. 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 volumes

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

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    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.

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

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    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.

  1. Analysis of spatial-temporal gene expression patterns reveals dynamics and regionalization in developing mouse brain.

    Science.gov (United States)

    Chou, Shen-Ju; Wang, Chindi; Sintupisut, Nardnisa; Niou, Zhen-Xian; Lin, Chih-Hsu; Li, Ker-Chau; Yeang, Chen-Hsiang

    2016-01-20

    Allen Brain Atlas (ABA) provides a valuable resource of spatial/temporal gene expressions in mammalian brains. Despite rich information extracted from this database, current analyses suffer from several limitations. First, most studies are either gene-centric or region-centric, thus are inadequate to capture the superposition of multiple spatial-temporal patterns. Second, standard tools of expression analysis such as matrix factorization can capture those patterns but do not explicitly incorporate spatial dependency. To overcome those limitations, we proposed a computational method to detect recurrent patterns in the spatial-temporal gene expression data of developing mouse brains. We demonstrated that regional distinction in brain development could be revealed by localized gene expression patterns. The patterns expressed in the forebrain, medullary and pontomedullary, and basal ganglia are enriched with genes involved in forebrain development, locomotory behavior, and dopamine metabolism respectively. In addition, the timing of global gene expression patterns reflects the general trends of molecular events in mouse brain development. Furthermore, we validated functional implications of the inferred patterns by showing genes sharing similar spatial-temporal expression patterns with Lhx2 exhibited differential expression in the embryonic forebrains of Lhx2 mutant mice. These analysis outcomes confirm the utility of recurrent expression patterns in studying brain development.

  2. 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.

  3. Evaluation of region selective bilirubin-induced brain damage as a basis for a pharmacological treatment

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    Dal Ben, Matteo; Bottin, Cristina; Zanconati, Fabrizio; Tiribelli, Claudio; Gazzin, Silvia

    2017-01-01

    The neurologic manifestations of neonatal hyperbilirubinemia in the central nervous system (CNS) exhibit high variations in the severity and appearance of motor, auditory and cognitive symptoms, which is suggestive of a still unexplained selective topography of bilirubin-induced damage. By applying the organotypic brain culture (OBC: preserving in vitro the cellular complexity, connection and architecture of the in vivo brain) technique to study hyperbilirubinemia, we mapped the regional target of bilirubin-induced damage, demonstrated a multifactorial toxic action of bilirubin, and used this information to evaluate the efficacy of drugs applicable to newborns to protect the brain. OBCs from 8-day-old rat pups showed a 2–13 fold higher sensitivity to bilirubin damage than 2-day-old preparations. The hippocampus, inferior colliculus and cerebral cortex were the only brain regions affected, presenting a mixed inflammatory-oxidative mechanism. Glutamate excitotoxicity was appreciable in only the hippocampus and inferior colliculus. Single drug treatment (indomethacin, curcumin, MgCl2) significantly improved cell viability in all regions, while the combined (cocktail) administration of the three drugs almost completely prevented damage in the most affected area (hippocampus). Our data may supports an innovative (complementary to phototherapy) approach for directly protecting the newborn brain from bilirubin neurotoxicity. PMID:28102362

  4. A Brain-Region-Specific Neural Pathway Regulating Germinal Matrix Angiogenesis.

    Science.gov (United States)

    Ma, Shang; Santhosh, Devi; Kumar T, Peeyush; Huang, Zhen

    2017-05-22

    Intimate communication between neural and vascular cells is critical for normal brain development and function. Germinal matrix (GM), a key primordium for the brain reward circuitry, is unique among brain regions for its distinct pace of angiogenesis and selective vulnerability to hemorrhage during development. A major neonatal condition, GM hemorrhage can lead to cerebral palsy, hydrocephalus, and mental retardation. Here we identify a brain-region-specific neural progenitor-based signaling pathway dedicated to regulating GM vessel development. This pathway consists of cell-surface sphingosine-1-phosphate receptors, an intracellular cascade including Gα co-factor Ric8a and p38 MAPK, and target gene integrin β8, which in turn regulates vascular TGF-β signaling. These findings provide insights into region-specific specialization of neurovascular communication, with special implications for deciphering potent early-life endocrine, as well as potential gut microbiota impacts on brain reward circuitry. They also identify tissue-specific molecular targets for GM hemorrhage intervention. Copyright © 2017 Elsevier Inc. All rights reserved.

  5. Brain regions responsible for tinnitus distress and loudness: a resting-state FMRI study.

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    Takashi Ueyama

    Full Text Available Subjective tinnitus is characterized by the perception of phantom sound without an external auditory stimulus. We hypothesized that abnormal functionally connected regions in the central nervous system might underlie the pathophysiology of chronic subjective tinnitus. Statistical significance of functional connectivity (FC strength is affected by the regional autocorrelation coefficient (AC. In this study, we used resting-state functional MRI (fMRI and measured regional mean FC strength (mean cross-correlation coefficient between a region and all other regions without taking into account the effect of AC (rGC and with taking into account the effect of AC (rGCa to elucidate brain regions related to tinnitus symptoms such as distress, depression and loudness. Consistent with previous studies, tinnitus loudness was not related to tinnitus-related distress and depressive state. Although both rGC and rGCa revealed similar brain regions where the values showed a statistically significant relationship with tinnitus-related symptoms, the regions for rGCa were more localized and more clearly delineated the regions related specifically to each symptom. The rGCa values in the bilateral rectus gyri were positively correlated and those in the bilateral anterior and middle cingulate gyri were negatively correlated with distress and depressive state. The rGCa values in the bilateral thalamus, the bilateral hippocampus, and the left caudate were positively correlated and those in the left medial superior frontal gyrus and the left posterior cingulate gyrus were negatively correlated with tinnitus loudness. These results suggest that distinct brain regions are responsible for tinnitus symptoms. The regions for distress and depressive state are known to be related to depression, while the regions for tinnitus loudness are known to be related to the default mode network and integration of multi-sensory information.

  6. Brain regions responsible for tinnitus distress and loudness: a resting-state FMRI study.

    Science.gov (United States)

    Ueyama, Takashi; Donishi, Tomohiro; Ukai, Satoshi; Ikeda, Yorihiko; Hotomi, Muneki; Yamanaka, Noboru; Shinosaki, Kazuhiro; Terada, Masaki; Kaneoke, Yoshiki

    2013-01-01

    Subjective tinnitus is characterized by the perception of phantom sound without an external auditory stimulus. We hypothesized that abnormal functionally connected regions in the central nervous system might underlie the pathophysiology of chronic subjective tinnitus. Statistical significance of functional connectivity (FC) strength is affected by the regional autocorrelation coefficient (AC). In this study, we used resting-state functional MRI (fMRI) and measured regional mean FC strength (mean cross-correlation coefficient between a region and all other regions without taking into account the effect of AC (rGC) and with taking into account the effect of AC (rGCa) to elucidate brain regions related to tinnitus symptoms such as distress, depression and loudness. Consistent with previous studies, tinnitus loudness was not related to tinnitus-related distress and depressive state. Although both rGC and rGCa revealed similar brain regions where the values showed a statistically significant relationship with tinnitus-related symptoms, the regions for rGCa were more localized and more clearly delineated the regions related specifically to each symptom. The rGCa values in the bilateral rectus gyri were positively correlated and those in the bilateral anterior and middle cingulate gyri were negatively correlated with distress and depressive state. The rGCa values in the bilateral thalamus, the bilateral hippocampus, and the left caudate were positively correlated and those in the left medial superior frontal gyrus and the left posterior cingulate gyrus were negatively correlated with tinnitus loudness. These results suggest that distinct brain regions are responsible for tinnitus symptoms. The regions for distress and depressive state are known to be related to depression, while the regions for tinnitus loudness are known to be related to the default mode network and integration of multi-sensory information.

  7. Brain-derived neurotrophic factor (BDNF) and its precursor (proBDNF) in genetically defined fear-induced aggression.

    Science.gov (United States)

    Ilchibaeva, Tatiana V; Kondaurova, Elena M; Tsybko, Anton S; Kozhemyakina, Rimma V; Popova, Nina K; Naumenko, Vladimir S

    2015-09-01

    The brain-derived neurotrophic factor (BDNF), its precursor (proBDNF) and BDNF mRNA levels were studied in the brain of wild rats selectively bred for more than 70 generations for either high level or for the lack of affective aggressiveness towards man. Significant increase of BDNF mRNA level in the frontal cortex and increase of BDNF level in the hippocampus of aggressive rats was revealed. In the midbrain and hippocampus of aggressive rats proBDNF level was increased, whereas BDNF/proBDNF ratio was reduced suggesting the prevalence and increased influence of proBDNF in highly aggressive rats. In the frontal cortex, proBDNF level in aggressive rats was decreased. Thus, considerable structure-specific differences in BDNF and proBDNF levels as well as in BDNF gene expression between highly aggressive and nonaggressive rats were shown. The data suggested the implication of BDNF and its precursor proBDNF in the mechanism of aggressiveness and in the creation of either aggressive or nonaggressive phenotype.

  8. Brain Regions and Neuropsychological Deficits in Obsessive-Compulsive Disorder

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    Murat Erdem

    2013-09-01

    Full Text Available Neurobiological factors had been shown to play an important role in the emergence of obsessive-compulsive disorder by the information obtained from the methods developed over the years. According to the neuropsychological perspective, the defects had been detected mainly in executive functions, in attention, memory, visual-spatial functions; and abnormalities had been described in the frontal lobe, cingulate cortex, basal ganglia, and thalamus regions of the patients with obsessive-compulsive disorder. The main and the most repeated abnormalities in patients with obsessive-compulsive disorder are dysfunctions in executive function and visual memory. Dysfunctions of the inhibitory processes associated with the dominant frontal area lead to an insufficiency on the inhibition of verbal functions. Excessive activation of the orbitofrontal cortex that mediate the behavioral response suppression function in obsessive-compulsive disorder demonstrated by functional imaging techniques. Repeated-resistant behaviors (eg: compulsions are composed by the deteriorations of the inhibitions of motor or cognitive programs in basal ganglions provided through cycles of frontal lobe. The findings of clinical observations in patients with obsessive-compulsive disorder could be considered as a reflection of excessive work in 'error detection system' which is the cause of the thoughts that something goes wrong and efforts to achieve perfection. As neurobiological, this finding is observed as excessive activity in orbitofrontal cortex and anterior cingulate cortex representing the ability of humans to provide and detect errors. It is is expected to develop the vehicles that are more sensitive to the characteristics of cognitive deficits in obsessive-compulsive disorder. In addition to the neuropsychological tests, using electrophysiological and advanced functional imaging techniques will put forward a better underlying the physiopathology of this disorder in order to

  9. Sonographic evaluation of overall and regional vascularization of fetal brain: a preliminary methodological study

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    M. Oberto

    2011-01-01

    Full Text Available The aim of this preliminary study is to develop a methodology to evaluate the vascularization of fetal brain in normal and abnormal canditions by three-dimensional sonography associated to Power Doppler (3DPD, with application of Virtual Organ Computer-aided Analysis (VOCAL that allows to derive vascularization and flow indexes. In this connction, we propose a new method of standardization of the setting and the acquisition mode, choosing in different fetuses and at different gestational ages the same anatomical volumes, corresponding to five spherical regions of interest. In particular, tu study the overall vascularization of the fetal brain, we use a sphere with a diameter corresponding to the bi-parietal distance. To evaluate the regional vascularization, we identify four sampling spherical sites, two in each hemisphere. This standard technical approach according to correct morphological criteria allows to exclude from the analysis vascular territories external to the brain.

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

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    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.

  11. Development of T2-relaxation values in regional brain sites during adolescence.

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    Kumar, Rajesh; Delshad, Sean; Macey, Paul M; Woo, Mary A; Harper, Ronald M

    2011-02-01

    Brain tissue changes accompany multiple neurodegenerative and developmental conditions in adolescents. Complex processes that occur in the developing brain with disease can be evaluated accurately only against normal aging processes. Normal developmental changes in different brain areas alter tissue water content, which can be assessed by magnetic resonance (MR) T2 relaxometry. We acquired proton-density (PD) and T2-weighted images from 31 subjects (mean age±S.D., 17.4±4.9 years; 18 male), using a 3.0-T MR imaging scanner. Voxel-by-voxel T2-relaxation values were calculated, and whole-brain T2-relaxation maps constructed and normalized to a common space template. We created a set of regions of interest (ROIs) over cortical gray and white matter, basal ganglia, amygdala, thalamic, hypothalamic, pontine and cerebellar sites, with sizes of ROIs varying from 12 to 243 mm(3); regional T2-relaxation values were determined from these ROIs and normalized T2-relaxation maps. Correlations between R2 (1/T2) values in these sites and age were assessed with Pearson's correlation procedures, and gender differences in regional T2-relaxation values were evaluated with independent-samples t tests. Several brain regions, but not all, showed principally positive correlations between R2 values and age; negative correlations emerged in the cerebellar peduncles. No significant differences in T2-relaxation values emerged between males and females for those areas, except for the mid pons and left occipital white matter; males showed higher T2-relaxation values over females. The findings indicate that T2-relaxation values vary with development between brain structures, and emphasize the need to correct for such age-related effects during any determination of potential changes from control values.

  12. 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.

  13. Adaptive integration of local region information to detect fine-scale brain activity patterns

    Institute of Scientific and Technical Information of China (English)

    2008-01-01

    With the rapid development of functional magnetic resonance imaging (fMRI) technology, the spatial resolution of fMRI data is continuously growing. This pro- vides us the possibility to detect the fine-scale patterns of brain activities. The es- tablished univariate and multivariate methods to analyze fMRI data mostly focus on detecting the activation blobs without considering the distributed fine-scale pat- terns within the blobs. To improve the sensitivity of the activation detection, in this paper, multivariate statistical method and univariate statistical method are com- bined to discover the fine-grained activity patterns. For one voxel in the brain, a local homogenous region is constructed. Then, time courses from the local ho- mogenous region are integrated with multivariate statistical method. Univariate statistical method is finally used to construct the interests of statistic for that voxel. The approach has explicitly taken into account the structures of both activity pat- terns and existing noise of local brain regions. Therefore, it could highlight the fine-scale activity patterns of the local regions. Experiments with simulated and real fMRI data demonstrate that the proposed method dramatically increases the sensitivity of detection of fine-scale brain activity patterns which contain the subtle information about experimental conditions.

  14. 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), cereb...

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

    Directory of Open Access Journals (Sweden)

    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.

  16. 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.

  17. 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.

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

    Science.gov (United States)

    Scott, Gregory D; Karns, Christina M; Dow, Mark W; Stevens, Courtney; Neville, Helen J

    2014-01-01

    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 vs. 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 vs. 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 (PPC), 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 congenitally deaf adults.

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

    Directory of Open Access Journals (Sweden)

    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

  20. The prefrontal cortex in the Göttingen minipig brain defined by neural projection criteria and cytoarchitecture

    DEFF Research Database (Denmark)

    Jelsing, J; Hay-Schmidt, Anders; Dyrby, Tim

    2006-01-01

    In an attempt to delineate the prefrontal cortex (PFC) in the Gottingen minipig brain the distribution of reciprocal thalamocortical projections was investigated using anterograde and retrograde tracing techniques and evaluated in relation to the specific cytoarchitectonic organization. Tracers...... were visualized using standard immunohistochemistry or evaluated in vivo using manganese (Mn2+) as an MRI paramagnetic tracer. The in vivo tract tracing turned out to be very sensitive with a high correspondence to the histological labelling. Tracers injected into the mediodorsal thalamus labelled...... connections to different parts of the MD nucleus. Although the granular layer IV, characteristic of primate PFC could not be identified, both cytoarchitectonic and connectional data suggests that the Gottingen minipig has a structurally divided prefrontal cortex. Stereological estimates of PFC volume showed...

  1. Defining seascapes for marine unconsolidated shelf sediments in an eastern boundary upwelling region: The southern Benguela as a case study

    Science.gov (United States)

    Karenyi, Natasha; Sink, Kerry; Nel, Ronel

    2016-02-01

    Marine unconsolidated sediment habitats, the largest benthic ecosystem, are considered physically controlled ecosystems driven by a number of local physical processes. Depth and sediment type are recognised key drivers of these ecosystems. Seascape (i.e., marine landscape) habitat classifications are based solely on consistent geophysical features and provide an opportunity to define unconsolidated sediment habitats based on processes which may vary in distribution through space and time. This paper aimed to classify unconsolidated sediment seascapes and explore their diversity in an eastern boundary upwelling region at the macro-scale, using the South African west coast as a case study. Physical variables such as sediment grain size, depth and upwelling-related variables (i.e., maximum chlorophyll concentration, austral summer bottom oxygen concentration and sediment organic carbon content) were included in the analyses. These variables were directly measured through sampling, or collated from existing databases and the literature. These data were analysed using multivariate Cluster, Principal Components Ordination and SIMPER analyses (in PRIMER 6 + with PERMANOVA add-in package). There were four main findings; (i) eight seascapes were identified for the South African west coast based on depth, slope, sediment grain size and upwelling-related variables, (ii) three depth zones were distinguished (inner, middle and outer shelf), (iii) seascape diversity in the inner and middle shelves was greater than the outer shelf, and (iv) upwelling-related variables were responsible for the habitat diversity in both inner and middle shelves. This research demonstrates that the inclusion of productivity and its related variables, such as hypoxia and sedimentary organic carbon, in seascape classifications will enhance the ability to distinguish seascapes on continental shelves, where productivity is most variable.

  2. Genomic androgen receptor-occupied regions with different functions, defined by histone acetylation, coregulators and transcriptional capacity.

    Directory of Open Access Journals (Sweden)

    Li Jia

    Full Text Available BACKGROUND: The androgen receptor (AR is a steroid-activated transcription factor that binds at specific DNA locations and plays a key role in the etiology of prostate cancer. While numerous studies have identified a clear connection between AR binding and expression of target genes for a limited number of loci, high-throughput elucidation of these sites allows for a deeper understanding of the complexities of this process. METHODOLOGY/PRINCIPAL FINDINGS: We have mapped 189 AR occupied regions (ARORs and 1,388 histone H3 acetylation (AcH3 loci to a 3% continuous stretch of human genomic DNA using chromatin immunoprecipitation (ChIP microarray analysis. Of 62 highly reproducible ARORs, 32 (52% were also marked by AcH3. While the number of ARORs detected in prostate cancer cells exceeded the number of nearby DHT-responsive genes, the AcH3 mark defined a subclass of ARORs much more highly associated with such genes -- 12% of the genes flanking AcH3+ARORs were DHT-responsive, compared to only 1% of genes flanking AcH3-ARORs. Most ARORs contained enhancer activities as detected in luciferase reporter assays. Analysis of the AROR sequences, followed by site-directed ChIP, identified binding sites for AR transcriptional coregulators FoxA1, CEBPbeta, NFI and GATA2, which had diverse effects on endogenous AR target gene expression levels in siRNA knockout experiments. CONCLUSIONS/SIGNIFICANCE: We suggest that only some ARORs function under the given physiological conditions, utilizing diverse mechanisms. This diversity points to differential regulation of gene expression by the same transcription factor related to the chromatin structure.

  3. Germline mutations of STR-alleles include multi-step mutations as defined by sequencing of repeat and flanking regions.

    Science.gov (United States)

    Dauber, Eva-Maria; Kratzer, Adelgunde; Neuhuber, Franz; Parson, Walther; Klintschar, Michael; Bär, Walter; Mayr, Wolfgang R

    2012-05-01

    Well defined estimates of mutation rates are a prerequisite for the use of short tandem repeat (STR-) loci in relationship testing. We investigated 65 isolated genetic inconsistencies, which were observed within 50,796 allelic transfers at 23 STR-loci (ACTBP2 (SE33), CD4, CSF1PO, F13A1, F13B, FES, FGA, vWA, TH01, TPOX, D2S1338, D3S1358, D5S818, D7S820, D8S1132, D8S1179, D12S391, D13S317, D16S539, D17S976, D18S51, D19S433, D21S11) in Caucasoid families residing in Austria and Switzerland. Sequencing data of repeat and flanking regions and the median of all theoretically possible mutational steps showed valuable information to characterise the mutational events with regard to parental origin, change of repeat number (mutational step size) and direction of mutation (losses and gains of repeats). Apart from predominant single-step mutations including one case with a double genetic inconsistency, two double-step and two apparent four-step mutations could be identified. More losses than gains of repeats and more mutations originating from the paternal than the maternal lineage were observed (31 losses, 22 gains, 12 losses or gains and 47 paternal, 11 maternal mutations and 7 unclear of parental origin). The mutation in the paternal germline was 3.3 times higher than in the maternal germline. The results of our study show, that apart from the vast majority of single-step mutations rare multi-step mutations can be observed. Therefore, the interpretation of mutational events should not rigidly be restricted to the shortest possible mutational step, because rare but true multi-step mutations can easily be overlooked, if haplotype analysis is not possible.

  4. 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.)

  5. Regional distribution of potassium, calcium, and six trace elements in normal human brain

    Energy Technology Data Exchange (ETDEWEB)

    Duflou, H.; Maenhaut, W.; De Reuck, J. (Institute for Nuclear Sciences, Gent (Belgium))

    1989-11-01

    Eight elements (i.e. K, Ca, Mn, Fe, Cu, Zn, Se, and Rb) were measured in 50 different regions of 12 normal human brains by particle-induced X-ray emission (PIXE) analysis. The dry weight concentrations of K, Fe, Cu, Zn, Se, and Rb were consistently higher for gray than for white matter areas. The K, Zn and Se concentrations for the regions of mixed composition and, to some extent, also the Rb concentrations, were intermediate between the gray and white matter values, and they tended to decrease with decreasing neuron density. The mean dry weight concentrations of K, Ca, Zn, Se, and Rb in the various brain regions were highly correlated with the mean wet-to-dry weight ratios of these regions. For Mn, Fe, and Cu, however, such a correlation was not observed, and these elements exhibited elevated levels in several structures of the basal ganglia. For K, Fe, and Se the concentrations seemed to change with age. A hierarchical cluster analysis indicated that the structures clustered into two large groups, one comprising gray and mixed matter regions, the other white and mixed matter areas. Brain structures involved in the same physiological function or morphologically similar regions often conglomerated in a single subcluster.

  6. Common and specific brain regions in high- versus low-confidence recognition memory

    Science.gov (United States)

    Kim, Hongkeun; Cabeza, Roberto

    2009-01-01

    The goal of the present functional magnetic resonance imaging (fMRI) study was to investigate whether and to what extent brain regions involved in high-confidence recognition (HCR) versus low-confidence recognition (LCR) overlap or separate from each other. To this end, we performed conjunction analyses involving activations elicited during high-confidence hit, low-confidence hit, and high-confidence correct-rejection responses. The analyses yielded 3 main findings. First, sensory/perceptual and associated posterior regions were common to HCR and LCR, indicating contribution of these regions to both HCR and LCR activity. This finding may help explain why these regions are among the most common in functional neuroimaging studies of episodic retrieval. Second, medial temporal lobe (MTL) and associated midline regions were associated with HCR, possibly reflecting recollection-related processes, whereas specific prefrontal cortex (PFC) regions were associated with LCR, possibly reflecting executive control processes. This finding is consistent with the notion that the MTL and PFC networks play complementary roles during episodic retrieval. Finally, within posterior parietal cortex, a dorsal region was associated with LCR, possibly reflecting top-down attentional processes, whereas a ventral region was associated with HCR, possibly reflecting bottom-up attentional processes. This finding may help explain why functional neuroimaging studies have found diverse parietal effects during episodic retrieval. Taken together, our findings provide strong evidence that HCR versus LCR, and by implication, recollection versus familiarity processes, are represented in common as well as specific brain regions. PMID:19501072

  7. Serotonin regulates brain-derived neurotrophic factor expression in select brain regions during acute psychological stress

    Institute of Scientific and Technical Information of China (English)

    De-guo Jiang; Shi-li Jin; Gong-ying Li; Qing-qing Li; Zhi-ruo Li; Hong-xia Ma; Chuan-jun Zhuo; Rong-huan Jiang; Min-jie Ye

    2016-01-01

    Previous studies suggest that serotonin (5-HT) might interact with brain-derived neurotrophic factor (BDNF) during the stress response. However, the relationship between 5-HT and BDNF expression under purely psychological stress is unclear. In this study, one hour before psychological stress exposure, the 5-HT1A receptor agonist 8-OH-DPAT or antagonist MDL73005, or the 5-HT2A receptor agonist DOI or antagonist ketanserin were administered to rats exposed to psychological stress. Immunohistochemistry andin situ hybridization revealed that after psychological stress, with the exception of the ventral tegmental area, BDNF protein and mRNA expression levels were higher in the 5-HT1A and the 5-HT2A receptor agonist groups compared with the solvent control no-stress or psychological stress group in the CA1 and CA3 of the hippocampus, prefrontal cortex, central amygdaloid nucleus, dorsomedial hypothalamic nucleus, dentate gyrus, shell of the nucleus accumbens and the midbrain periaqueductal gray. There was no signiifcant difference between the two agonist groups. In contrast, after stress exposure, BDNF protein and mRNA expression levels were lower in the 5-HT1A and 5-HT2A receptor antagonist groups than in the solvent control non-stress group, with the exception of the ventral tegmental area. Our ifndings suggest that 5-HT regulates BDNF expression in a rat model of acute psychological stress.

  8. Serotonin regulates brain-derived neurotrophic factor expression in select brain regions during acute psychological stress

    Directory of Open Access Journals (Sweden)

    De-guo Jiang

    2016-01-01

    Full Text Available Previous studies suggest that serotonin (5-HT might interact with brain-derived neurotrophic factor (BDNF during the stress response. However, the relationship between 5-HT and BDNF expression under purely psychological stress is unclear. In this study, one hour before psychological stress exposure, the 5-HT1A receptor agonist 8-OH-DPAT or antagonist MDL73005, or the 5-HT2A receptor agonist DOI or antagonist ketanserin were administered to rats exposed to psychological stress. Immunohistochemistry and in situ hybridization revealed that after psychological stress, with the exception of the ventral tegmental area, BDNF protein and mRNA expression levels were higher in the 5-HT1A and the 5-HT2A receptor agonist groups compared with the solvent control no-stress or psychological stress group in the CA1 and CA3 of the hippocampus, prefrontal cortex, central amygdaloid nucleus, dorsomedial hypothalamic nucleus, dentate gyrus, shell of the nucleus accumbens and the midbrain periaqueductal gray. There was no significant difference between the two agonist groups. In contrast, after stress exposure, BDNF protein and mRNA expression levels were lower in the 5-HT1A and 5-HT2A receptor antagonist groups than in the solvent control non-stress group, with the exception of the ventral tegmental area. Our findings suggest that 5-HT regulates BDNF expression in a rat model of acute psychological stress.

  9. Serotonin regulates brain-derived neurotrophic factor expression in select brain regions during acute psychological stress.

    Science.gov (United States)

    Jiang, De-Guo; Jin, Shi-Li; Li, Gong-Ying; Li, Qing-Qing; Li, Zhi-Ruo; Ma, Hong-Xia; Zhuo, Chuan-Jun; Jiang, Rong-Huan; Ye, Min-Jie

    2016-09-01

    Previous studies suggest that serotonin (5-HT) might interact with brain-derived neurotrophic factor (BDNF) during the stress response. However, the relationship between 5-HT and BDNF expression under purely psychological stress is unclear. In this study, one hour before psychological stress exposure, the 5-HT1A receptor agonist 8-OH-DPAT or antagonist MDL73005, or the 5-HT2A receptor agonist DOI or antagonist ketanserin were administered to rats exposed to psychological stress. Immunohistochemistry and in situ hybridization revealed that after psychological stress, with the exception of the ventral tegmental area, BDNF protein and mRNA expression levels were higher in the 5-HT1A and the 5-HT2A receptor agonist groups compared with the solvent control no-stress or psychological stress group in the CA1 and CA3 of the hippocampus, prefrontal cortex, central amygdaloid nucleus, dorsomedial hypothalamic nucleus, dentate gyrus, shell of the nucleus accumbens and the midbrain periaqueductal gray. There was no significant difference between the two agonist groups. In contrast, after stress exposure, BDNF protein and mRNA expression levels were lower in the 5-HT1A and 5-HT2A receptor antagonist groups than in the solvent control non-stress group, with the exception of the ventral tegmental area. Our findings suggest that 5-HT regulates BDNF expression in a rat model of acute psychological stress.

  10. Altered regional connectivity reflecting effects of different anaesthesia protocols in the mouse brain.

    Science.gov (United States)

    Wu, Tong; Grandjean, Joanes; Bosshard, Simone C; Rudin, Markus; Reutens, David; Jiang, Tianzi

    2017-02-01

    Studies in mice using resting-state functional magnetic resonance imaging (rs-fMRI) have provided opportunities to investigate the effects of pharmacological manipulations on brain function and map the phenotypes of mouse models of human brain disorders. Mouse rs-fMRI is typically performed under anaesthesia, which induces both regional suppression of brain activity and disruption of large-scale neural networks. Previous comparative studies using rodents investigating various drug effects on long-distance functional connectivity (FC) have reported agent-specific FC patterns, however, effects of regional suppression are sparsely explored. Here we examined changes in regional connectivity under six different anaesthesia conditions using mouse rs-fMRI with the goal of refining the framework of understanding the brain activation under anaesthesia at a local level. Regional homogeneity (ReHo) was used to map local synchronization in the brain, followed by analysis of several brain areas based on ReHo maps. The results revealed high local coherence in most brain areas. The primary somatosensory cortex and caudate-putamen showed agent-specific properties. Lower local coherence in the cingulate cortex was observed under medetomidine, particularly when compared to the combination of medetomidine and isoflurane. The thalamus was associated with retained local coherence across anaesthetic levels and multiple nuclei. These results show that anaesthesia induced by the investigated anaesthetics through different molecular targets promote agent-specific regional connectivity. In addition, ReHo is a data-driven method with minimum user interaction, easy to use and fast to compute. Given that examination of the brain at a local level is widely applied in human rs-fMRI studies, our results show its sensitivity to extract information on varied neuronal activity under six different regimens relevant to mouse functional imaging. These results, therefore, will inform future rs

  11. Motion sickness increases functional connectivity between visual motion and nausea-associated brain regions.

    Science.gov (United States)

    Toschi, Nicola; Kim, Jieun; Sclocco, Roberta; Duggento, Andrea; Barbieri, Riccardo; Kuo, Braden; Napadow, Vitaly

    2017-01-01

    The brain networks supporting nausea not yet understood. We previously found that while visual stimulation activated primary (V1) and extrastriate visual cortices (MT+/V5, coding for visual motion), increasing nausea was associated with increasing sustained activation in several brain areas, with significant co-activation for anterior insula (aIns) and mid-cingulate (MCC) cortices. Here, we hypothesized that motion sickness also alters functional connectivity between visual motion and previously identified nausea-processing brain regions. Subjects prone to motion sickness and controls completed a motion sickness provocation task during fMRI/ECG acquisition. We studied changes in connectivity between visual processing areas activated by the stimulus (MT+/V5, V1), right aIns and MCC when comparing rest (BASELINE) to peak nausea state (NAUSEA). Compared to BASELINE, NAUSEA reduced connectivity between right and left V1 and increased connectivity between right MT+/V5 and aIns and between left MT+/V5 and MCC. Additionally, the change in MT+/V5 to insula connectivity was significantly associated with a change in sympathovagal balance, assessed by heart rate variability analysis. No state-related connectivity changes were noted for the control group. Increased connectivity between a visual motion processing region and nausea/salience brain regions may reflect increased transfer of visual/vestibular mismatch information to brain regions supporting nausea perception and autonomic processing. We conclude that vection-induced nausea increases connectivity between nausea-processing regions and those activated by the nauseogenic stimulus. This enhanced low-frequency coupling may support continual, slowly evolving nausea perception and shifts toward sympathetic dominance. Disengaging this coupling may be a target for biobehavioral interventions aimed at reducing motion sickness severity. Copyright © 2016 Elsevier B.V. All rights reserved.

  12. Blood-brain barrier to peptides: (/sup 3/H)gonadotropin-releasing hormone accumulation by eighteen regions of the rat brain and by anterior pituitary

    Energy Technology Data Exchange (ETDEWEB)

    Ermisch, A.; Ruehle, H.J. (Karl-Marx-Universitaet, Leipzig (German Democratic Republic). Sektion Biowissenschaften); Klauschenz, E.; Kretzschmar, R. (Akademie der Wissenschaften der DDR, Berlin. Inst. fuer Wirkstofforschung)

    1984-01-01

    After intracarotid injection of (/sup 3/H)gonadotropin-releasing hormone ((/sup 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/sup -1/ of the injected tracer dose. This indicates a low but measurable brain uptake of the peptide. The brain uptake of (/sup 3/H)GnRH in blood-brain barrier (BBB)-protected regions is 5% of that of separately investigated (/sup 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 (/sup 3/H)GnRH among regions with BBB varies less than among regions with leaky endothelia. The data presented for (/sup 3/H)GnRH are similar to those for other peptides so far investigated.

  13. 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.

  14. Attention Performance Measured by Attention Network Test is Correlated with Global and Regional Efficiency of Structural Human Brain Networks

    Directory of Open Access Journals (Sweden)

    Min Xiao

    2016-10-01

    Full Text Available Functional neuroimaging studies have indicated the involvement of separate brain areas in three distinct attention systems: alerting, orienting and executive control (EC. However, the structural correlates underlying attention remains unexplored. Here, we utilized graph theory to examine the neuroanatomical substrates of the three attention systems measured by attention network test (ANT in 65 healthy subjects. White matter connectivity, assessed with DTI deterministic tractography was modeled as a structural network comprising 90 nodes defined by the Automated Anatomical Labeling (AAL template. Linear regression analyses were conducted to explore the relationship between topological parameters and the three attentional effects. We found a significant positive correlation between EC function and global efficiency of the whole brain network. At the regional level, node-specific correlations were discovered between regional efficiency and all three ANT components, including dorsolateral superior frontal gyrus, thalamus and parahippocampal gyrus for EC, thalamus and inferior parietal gyrus for alerting, and paracentral lobule and inferior occipital gyrus for orienting. Our findings highlight the fundamental architecture of interregional structural connectivity involved in attention and could provide new insights into the anatomical basis underlying human behavior.

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

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    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

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

    Science.gov (United States)

    Egorova, Natalia; Gollub, Randy L; Kong, Jian

    2015-01-01

    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.

  17. Early development of arterial spin labeling to measure regional brain blood flow by MRI.

    Science.gov (United States)

    Koretsky, Alan P

    2012-08-15

    Two major avenues of work converged in the late 1980's and early 1990's to give rise to brain perfusion MRI. The development of anatomical brain MRI quickly had as a major goal the generation of angiograms using tricks to label flowing blood in macroscopic vessels. These ideas were aimed at getting information about microcirculatory flow as well. Over the same time course the development of in vivo magnetic resonance spectroscopy had as its primary goal the assessment of tissue function and in particular, tissue energetics. For this the measurement of the delivery of water to tissue was critical for assessing tissue oxygenation and viability. The measurement of the washin/washout of "freely" diffusible tracers by spectroscopic based techniques pointed the way for quantitative approaches to measure regional blood flow by MRI. These two avenues came together in the development of arterial spin labeling (ASL) MRI techniques to measure regional cerebral blood flow. The early use of ASL to measure brain activation to help verify BOLD fMRI led to a rapid development of ASL based perfusion MRI. Today development and applications of regional brain blood flow measurements with ASL continues to be a major area of activity.

  18. 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.

  19. Propofol Affects Different Human Brain Regions Depending on Depth of Sedation

    Institute of Scientific and Technical Information of China (English)

    Xiang Quan; Tie-hu Ye; Si-fang Lin; Liang Zou; Shou-yuan Tian

    2015-01-01

    Objective To investigate the effect of propofol on brain regions at different sedation levels and the association between changes in brain region activity and loss of consciousness using blood oxygen level-dependent functional magnetic resonance imaging (BOLD-fMRI) and bispectral index (BIS) monitoring. Methods Forty-eight participants were enrolled at Peking Union Medical College Hospital from October 2011 to March 2012 and randomly assigned to a mild or a deep sedation group using computer- generated random numbers. Preliminary tests were performed a week prior to scanning to determine target effect site concentrations based on BIS and concomitant Observer's Assessment of Alertness/Sedation scores while under propofol. Within one week of the preliminary tests where propofol dose-response was established, BOLD-fMRI was conducted to examine brain activation with the subject awake, and with propofol infusion at the sedation level. Results Mild propofol sedation inhibited left inferior parietal lobe activation. Deep sedation inhibited activation of the left insula, left superior temporal gyrus, and right middle temporal gyrus. Compared with mild sedation, deep propofol sedation inhibited activation of the left thalamus, precentral gyrus, anterior cingulate, and right basal nuclei. Conclusion Mild and deep propofol sedation are associated with inhibition of different brain regions, possibly explaining differences in the respective loss of consciousness processes.

  20. 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......, and we were unable to identify a spectral signature at 1.30 ppm previously suggested to reflect neurogenesis induced by ECT. None of the brain imaging measures correlated to the clinical response. Conclusion: Our findings show that ECT causes a remodeling of brain structures involved in affective...

  1. 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…

  2. Aberrant Global and Regional Topological Organization of the Fractional Anisotropy-weighted Brain Structural Networks in Major Depressive Disorder

    Institute of Scientific and Technical Information of China (English)

    Jian-Huai Chen; Zhi-Jian Yao; Jiao-Long Qin; Rui Yan; Ling-Ling Hua; Qing Lu

    2016-01-01

    Background:Most previous neuroimaging studies have focused on the structural and functional abnormalities of local brain regions in major depressive disorder (MDD).Moreover,the exactly topological organization of networks underlying MDD remains unclear.This study examined the aberrant global and regional topological patterns of the brain white matter networks in MDD patients.Methods:The diffusion tensor imaging data were obtained from 27 patients with MDD and 40 healthy controls.The brain fractional anisotropy-weighted structural networks were constructed,and the global network and regional nodal metrics of the networks were explored by the complex network theory.Results:Compared with the healthy controls,the brain structural network of MDD patients showed an intact small-world topology,but significantly abnormal global network topological organization and regional nodal characteristic of the network in MDD were found.Our findings also indicated that the brain structural networks in MDD patients become a less strongly integrated network with a reduced central role of some key brain regions.Conclusions:All these resulted in a less optimal topological organization of networks underlying MDD patients,including an impaired capability of local information processing,reduced centrality of some brain regions and limited capacity to integrate information across different regions.Thus,these global network and regional node-level aberrations might contribute to understanding the pathogenesis of MDD from the view of the brain network.

  3. 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…

  4. Distribution of ionic currents in the soma and growing region of an identified peptidergic neuron in defined culture.

    Science.gov (United States)

    Meyers, D E

    1993-02-01

    1. Somata and lamellipodia of a distinct type of crustacean peptidergic neuron were isolated by severing the connecting neurite. The whole-cell variation of the patch-clamp technique was then used to study the electrical activity and ionic currents of each part. Neurons were enzymatically isolated from the X-organ of Cardisoma carnifex and cultured in defined medium. The neurons studied were recognizable by their large ovoid somata (approximately 35 microns minor diam) and broad, flat lamellipodium regrown from the remaining neurite. These cells are immunopositive against crustacean hyperglycemic hormone (CHH) antisera. Recordings were made 18-30 h after plating. 2. In current-clamp recordings, 10 of 12 lamellipodia fired overshooting action potentials (mean half width = 8.2 +/- 2.9 ms, mean +/- SD), whereas only two of seven somata did so. Spontaneous activity in isolated somata and lamellipodia was rarely encountered. The action potential in isolated lamellipodia has both Na+ and Ca2+ components, whereas the regenerative activity recorded in isolated somata was predominantly Ca(2+)-based. 3. The inward currents examined under voltage clamp consisted of Na current (INa) and Ca current (ICa). Both currents could be resolved in isolated somata and lamellipodia. INa was completely blocked by tetrodotoxin [TTX (1 microM)]. The INa density in lamellipodia was approximately 4-19 times greater than that of the somata from which they had been separated. In contrast, ICa density in lamellipodia was two to five times smaller than that of somata. The properties of ICa were similar in both somata and lamellipodia, with the exception that ICa in lamellipodia did not recover after large depolarizing prepulses. 4. Two types of outward current were readily identified under voltage clamp. These were the transient 4-aminopyridine-sensitive current and the delayed outward current that was partially sensitive to tetraethylammonium ions. The peak potassium current-density ratio for

  5. Gene expression profiles in rat brain disclose CNS signature genes and regional patterns of functional specialisation

    Directory of Open Access Journals (Sweden)

    Breilid Harald

    2007-04-01

    Full Text Available Abstract Background The mammalian brain is divided into distinct regions with structural and neurophysiological differences. As a result, gene expression is likely to vary between regions in relation to their cellular composition and neuronal function. In order to improve our knowledge and understanding of regional patterns of gene expression in the CNS, we have generated a global map of gene expression in selected regions of the adult rat brain (frontomedial-, temporal- and occipital cortex, hippocampus, striatum and cerebellum; both right and left sides as well as in three major non-neural tissues (spleen, liver and kidney using the Applied Biosystems Rat Genome Survey Microarray. Results By unsupervised hierarchical clustering, we found that the transcriptome within a region was highly conserved among individual rats and that there were no systematic differences between the two hemispheres (right versus left side. Further, we identified distinct sets of genes showing significant regional enrichment. Functional annotation of each of these gene sets clearly reflected several important physiological features of the region in question, including synaptic transmission within the cortex, neurogenesis in hippocampus and G-protein-mediated signalling in striatum. In addition, we were able to reveal potentially new regional features, such as mRNA transcription- and neurogenesis-annotated activities in cerebellum and differential use of glutamate signalling between regions. Finally, we determined a set of 'CNS-signature' genes that uncover characteristics of several common neuronal processes in the CNS, with marked over-representation of specific features of synaptic transmission, ion transport and cell communication, as well as numerous novel unclassified genes. Conclusion We have generated a global map of gene expression in the rat brain and used this to determine functional processes and pathways that have a regional preference or ubiquitous

  6. Modeling Causal Relationship Between Brain Regions Within the Drug-Cue Processing Network in Chronic Cocaine Smokers.

    Science.gov (United States)

    Ray, Suchismita; Haney, Margaret; Hanson, Catherine; Biswal, Bharat; Hanson, Stephen José

    2015-12-01

    The cues associated with drugs of abuse have an essential role in perpetuating problematic use, yet effective connectivity or the causal interaction between brain regions mediating the processing of drug cues has not been defined. The aim of this fMRI study was to model the causal interaction between brain regions within the drug-cue processing network in chronic cocaine smokers and matched control participants during a cocaine-cue exposure task. Specifically, cocaine-smoking (15M; 5F) and healthy control (13M; 4F) participants viewed cocaine and neutral cues while in the scanner (a Siemens 3 T magnet). We examined whole brain activation, including activation related to drug-cue processing. Time series data extracted from ROIs determined through our General Linear Model (GLM) analysis and prior publications were used as input to IMaGES, a computationally powerful Bayesian search algorithm. During cocaine-cue exposure, cocaine users showed a particular feed-forward effective connectivity pattern between the ROIs of the drug-cue processing network (amygdala → hippocampus → dorsal striatum → insula → medial frontal cortex, dorsolateral prefrontal cortex, anterior cingulate cortex) that was not present when the controls viewed the cocaine cues. Cocaine craving ratings positively correlated with the strength of the causal influence of the insula on the dorsolateral prefrontal cortex in cocaine users. This study is the first demonstration of a causal interaction between ROIs within the drug-cue processing network in cocaine users. This study provides insight into the mechanism underlying continued substance use and has implications for monitoring treatment response.

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

    DEFF Research Database (Denmark)

    Kerbl, Alexandra; Martín-Durán, José M.; Worsaae, Katrine;

    2016-01-01

    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...

  8. Brain volumes and regional cortical thickness in young females with anorexia nervosa.

    Science.gov (United States)

    Fuglset, Tone Seim; Endestad, Tor; Hilland, Eva; Bang, Lasse; Tamnes, Christian Krog; Landrø, Nils Inge; Rø, Øyvind

    2016-11-16

    Anorexia nervosa (AN) is a severe mental illness, with an unknown etiology. Magnetic resonance imaging studies show reduced brain volumes and cortical thickness in patients compared to healthy controls. However, findings are inconsistent, especially concerning the anatomical location and extent of the differences. The purpose of this study was to estimate and compare brain volumes and regional cortical thickness in young females with AN and healthy controls. Magnetic resonance imaging data was acquired from young females with anorexia nervosa (n = 23) and healthy controls (n = 28). Two different scanner sites were used. BMI varied from 13.5 to 20.7 within the patient group, and 11 patients had a BMI > 17.5. FreeSurfer was used to estimate brain volumes and regional cortical thickness. There were no differences between groups in total cerebral cortex volume, white matter volume, or lateral ventricle volume. There were also no volume differences in subcortical grey matter structures. However the results showed reduced cortical thickness bilaterally in the superior parietal gyrus, and in the right inferior parietal and superior frontal gyri. The functional significance of the findings is undetermined as the majority of the included patients was already partially weight-restored. We discuss whether these regions could be related to predisposing factors of the illness, or whether they are regions that are more vulnerable to starvation, malnutrition or associated processes in AN.

  9. Trajectories of brain aging in middle-aged and older adults: regional and individual differences.

    Science.gov (United States)

    Raz, Naftali; Ghisletta, Paolo; Rodrigue, Karen M; Kennedy, Kristen M; Lindenberger, Ulman

    2010-06-01

    The human brain changes with age. However, the rate and the trajectories of change vary among the brain regions and among individuals, and the reasons for these differences are unclear. In a sample of healthy middle-aged and older adults, we examined mean volume change and individual differences in the rate of change in 12 regional brain volumes over approximately 30 months. In addition to the baseline assessment, there were two follow-ups, 15 months apart. We observed significant average shrinkage of the hippocampus, entorhinal cortex, orbital-frontal cortex, and cerebellum in each of the intervals. Shrinkage of the hippocampus accelerated with time, whereas shrinkage of the caudate nucleus, prefrontal subcortical white matter, and corpus callosum emerged only at the second follow-up. Throughout both assessment intervals, the mean volumes of the lateral prefrontal and primary visual cortices, putamen, and pons did not change. Significant individual differences in shrinkage rates were observed in the lateral prefrontal cortex, the cerebellum, and all the white matter regions throughout the study, whereas additional regions (medial-temporal structures, the insula, and the basal ganglia) showed significant individual variation in change during the second follow-up. No individual variability was noted in the change of orbital frontal and visual cortices. In two white matter regions, we were able to identify factors associated with individual differences in brain shrinkage. In corpus callosum, shrinkage rate was greater in persons with hypertension, and in the pons, women and carriers of the ApoEepsilon4 allele exhibited declines not noted in the whole sample.

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

    Directory of Open Access Journals (Sweden)

    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

  11. 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

  12. A regional consensus recommendation on brain atrophy as an outcome measure in multiple sclerosis.

    Science.gov (United States)

    Alroughani, Raed; Deleu, Dirk; El Salem, Khalid; Al-Hashel, Jasem; Alexander, K John; Abdelrazek, Mohamed Assem; Aljishi, Adel; Alkhaboori, Jaber; Al Azri, Faisal; Al Zadjali, Nahida; Hbahbih, Majed; Sokrab, Tag Eldin; Said, Mohamed; Rovira, Àlex

    2016-11-24

    Multiple sclerosis (MS) is a chronic autoimmune disease characterized by inflammatory and neurodegenerative processes leading to irreversible neurological impairment. Brain atrophy occurs early in the course of the disease at a rate greater than the general population. Brain volume loss (BVL) is associated with disability progression and cognitive impairment in patients with MS; hence its value as a potential target in monitoring and treating MS is discussed. A group of MS neurologists and neuro-radiologists reviewed the current literature on brain atrophy and discussed the challenges in assessing and implementing brain atrophy measurements in clinical practice. The panel used a voting system to reach a consensus and the votes were counted for the proposed set of questions for cognitive and brain atrophy assessments. The panel of experts was able to identify recent studies, which demonstrated the correlation between BVL and future worsening of disability and cognition. The current evidence revealed that reduction of BVL could be achieved with different disease-modifying therapies (DMTs). BVL provided a better treatment and monitoring strategy when it is combined to the composite measures of "no evidence of disease activity" (NEDA). The panel recommended a set of cognitive assessment tools and MRI methods and software applications that may help in capturing and measuring the underlying MS pathology with high degree of specificity. BVL was considered to be a useful measurement to longitudinally assess disease progression and cognitive function in patients with MS. Brain atrophy measurement was recommended to be incorporated into the concept of NEDA. Consequently, a consensus recommendation was reached in anticipation for implementation of the use of cognitive assessment and brain atrophy measurements on a regional level.

  13. Enhanced Performance of Brain Tumor Classification via Tumor Region Augmentation and Partition.

    Directory of Open Access Journals (Sweden)

    Jun Cheng

    Full Text Available Automatic classification of tissue types of region of interest (ROI plays an important role in computer-aided diagnosis. In the current study, we focus on the classification of three types of brain tumors (i.e., meningioma, glioma, and pituitary tumor in T1-weighted contrast-enhanced MRI (CE-MRI images. Spatial pyramid matching (SPM, which splits the image into increasingly fine rectangular subregions and computes histograms of local features from each subregion, exhibits excellent results for natural scene classification. However, this approach is not applicable for brain tumors, because of the great variations in tumor shape and size. In this paper, we propose a method to enhance the classification performance. First, the augmented tumor region via image dilation is used as the ROI instead of the original tumor region because tumor surrounding tissues can also offer important clues for tumor types. Second, the augmented tumor region is split into increasingly fine ring-form subregions. We evaluate the efficacy of the proposed method on a large dataset with three feature extraction methods, namely, intensity histogram, gray level co-occurrence matrix (GLCM, and bag-of-words (BoW model. Compared with using tumor region as ROI, using augmented tumor region as ROI improves the accuracies to 82.31% from 71.39%, 84.75% from 78.18%, and 88.19% from 83.54% for intensity histogram, GLCM, and BoW model, respectively. In addition to region augmentation, ring-form partition can further improve the accuracies up to 87.54%, 89.72%, and 91.28%. These experimental results demonstrate that the proposed method is feasible and effective for the classification of brain tumors in T1-weighted CE-MRI.

  14. Regional brain differences in cortical thickness, surface area and subcortical volume in individuals with Williams syndrome.

    Science.gov (United States)

    Meda, Shashwath A; Pryweller, Jennifer R; Thornton-Wells, Tricia A

    2012-01-01

    Williams syndrome (WS) is a rare genetic neurodevelopmental disorder characterized by increased non-social anxiety, sensitivity to sounds and hypersociability. Previous studies have reported contradictory findings with regard to regional brain variation in WS, relying on only one type of morphological measure (usually volume) in each study. The present study aims to contribute to this body of literature and perhaps elucidate some of these discrepancies by examining concurrent measures of cortical thickness, surface area and subcortical volume between WS subjects and typically-developing (TD) controls. High resolution MRI scans were obtained on 31 WS subjects and 50 typically developing control subjects. We derived quantitative regional estimates of cortical thickness, cortical surface area, and subcortical volume using FreeSurfer software. We evaluated between-group ROI differences while controlling for total intracranial volume. In post-hoc exploratory analyses within the WS group, we tested for correlations between regional brain variation and Beck Anxiety Inventory scores. Consistent with our hypothesis, we detected complex patterns of between-group cortical variation, which included lower surface area in combination with greater thickness in the following cortical regions: post central gyrus, cuneus, lateral orbitofrontal cortex and lingual gyrus. Additional cortical regions showed between-group differences in one (but not both) morphological measures. Subcortical volume was lower in the basal ganglia and the hippocampus in WS versus TD controls. Exploratory correlations revealed that anxiety scores were negatively correlated with gray matter surface area in insula, OFC, rostral middle frontal, superior temporal and lingual gyrus. Our results were consistent with previous reports showing structural alterations in regions supporting the socio-affective and visuospatial impairments in WS. However, we also were able to effectively capture novel and complex

  15. Enhanced Performance of Brain Tumor Classification via Tumor Region Augmentation and Partition.

    Science.gov (United States)

    Cheng, Jun; Huang, Wei; Cao, Shuangliang; Yang, Ru; Yang, Wei; Yun, Zhaoqiang; Wang, Zhijian; Feng, Qianjin

    2015-01-01

    Automatic classification of tissue types of region of interest (ROI) plays an important role in computer-aided diagnosis. In the current study, we focus on the classification of three types of brain tumors (i.e., meningioma, glioma, and pituitary tumor) in T1-weighted contrast-enhanced MRI (CE-MRI) images. Spatial pyramid matching (SPM), which splits the image into increasingly fine rectangular subregions and computes histograms of local features from each subregion, exhibits excellent results for natural scene classification. However, this approach is not applicable for brain tumors, because of the great variations in tumor shape and size. In this paper, we propose a method to enhance the classification performance. First, the augmented tumor region via image dilation is used as the ROI instead of the original tumor region because tumor surrounding tissues can also offer important clues for tumor types. Second, the augmented tumor region is split into increasingly fine ring-form subregions. We evaluate the efficacy of the proposed method on a large dataset with three feature extraction methods, namely, intensity histogram, gray level co-occurrence matrix (GLCM), and bag-of-words (BoW) model. Compared with using tumor region as ROI, using augmented tumor region as ROI improves the accuracies to 82.31% from 71.39%, 84.75% from 78.18%, and 88.19% from 83.54% for intensity histogram, GLCM, and BoW model, respectively. In addition to region augmentation, ring-form partition can further improve the accuracies up to 87.54%, 89.72%, and 91.28%. These experimental results demonstrate that the proposed method is feasible and effective for the classification of brain tumors in T1-weighted CE-MRI.

  16. Regional brain differences in cortical thickness, surface area and subcortical volume in individuals with Williams syndrome.

    Directory of Open Access Journals (Sweden)

    Shashwath A Meda

    Full Text Available Williams syndrome (WS is a rare genetic neurodevelopmental disorder characterized by increased non-social anxiety, sensitivity to sounds and hypersociability. Previous studies have reported contradictory findings with regard to regional brain variation in WS, relying on only one type of morphological measure (usually volume in each study. The present study aims to contribute to this body of literature and perhaps elucidate some of these discrepancies by examining concurrent measures of cortical thickness, surface area and subcortical volume between WS subjects and typically-developing (TD controls. High resolution MRI scans were obtained on 31 WS subjects and 50 typically developing control subjects. We derived quantitative regional estimates of cortical thickness, cortical surface area, and subcortical volume using FreeSurfer software. We evaluated between-group ROI differences while controlling for total intracranial volume. In post-hoc exploratory analyses within the WS group, we tested for correlations between regional brain variation and Beck Anxiety Inventory scores. Consistent with our hypothesis, we detected complex patterns of between-group cortical variation, which included lower surface area in combination with greater thickness in the following cortical regions: post central gyrus, cuneus, lateral orbitofrontal cortex and lingual gyrus. Additional cortical regions showed between-group differences in one (but not both morphological measures. Subcortical volume was lower in the basal ganglia and the hippocampus in WS versus TD controls. Exploratory correlations revealed that anxiety scores were negatively correlated with gray matter surface area in insula, OFC, rostral middle frontal, superior temporal and lingual gyrus. Our results were consistent with previous reports showing structural alterations in regions supporting the socio-affective and visuospatial impairments in WS. However, we also were able to effectively capture novel and

  17. Whole transcriptome sequencing reveals gene expression and splicing differences in brain regions affected by Alzheimer's disease.

    Directory of Open Access Journals (Sweden)

    Natalie A Twine

    Full Text Available Recent studies strongly indicate that aberrations in the control of gene expression might contribute to the initiation and progression of Alzheimer's disease (AD. In particular, alternative splicing has been suggested to play a role in spontaneous cases of AD. Previous transcriptome profiling of AD models and patient samples using microarrays delivered conflicting results. This study provides, for the first time, transcriptomic analysis for distinct regions of the AD brain using RNA-Seq next-generation sequencing technology. Illumina RNA-Seq analysis was used to survey transcriptome profiles from total brain, frontal and temporal lobe of healthy and AD post-mortem tissue. We quantified gene expression levels, splicing isoforms and alternative transcript start sites. Gene Ontology term enrichment analysis revealed an overrepresentation of genes associated with a neuron's cytological structure and synapse function in AD brain samples. Analysis of the temporal lobe with the Cufflinks tool revealed that transcriptional isoforms of the apolipoprotein E gene, APOE-001, -002 and -005, are under the control of different promoters in normal and AD brain tissue. We also observed differing expression levels of APOE-001 and -002 splice variants in the AD temporal lobe. Our results indicate that alternative splicing and promoter usage of the APOE gene in AD brain tissue might reflect the progression of neurodegeneration.

  18. Global and regional differences in brain anatomy of young children born small for gestational age.

    Directory of Open Access Journals (Sweden)

    Henrica M A De Bie

    Full Text Available In children who are born small for gestational age (SGA, an adverse intrauterine environment has led to underdevelopment of both the body and the brain. The delay in body growth is (partially restored during the first two years in a majority of these children. In addition to a negative influence on these physical parameters, decreased levels of intelligence and cognitive impairments have been described in children born SGA. In this study, we used magnetic resonance imaging to examine brain anatomy in 4- to 7-year-old SGA children with and without complete bodily catch-up growth and compared them to healthy children born appropriate for gestational age. Our findings demonstrate that these children strongly differ on brain organisation when compared with healthy controls relating to both global and regional anatomical differences. Children born SGA displayed reduced cerebral and cerebellar grey and white matter volumes, smaller volumes of subcortical structures and reduced cortical surface area. Regional differences in prefrontal cortical thickness suggest a different development of the cerebral cortex. SGA children with bodily catch-up growth constitute an intermediate between those children without catch-up growth and healthy controls. Therefore, bodily catch-up growth in children born SGA does not implicate full catch-up growth of the brain.

  19. Witnessing hateful people in pain modulates brain activity in regions associated with physical pain and reward.

    Directory of Open Access Journals (Sweden)

    Glenn Ryan Fox

    2013-10-01

    Full Text Available How does witnessing a hateful person in pain compare to witnessing a likable person in pain? The current study compared the brain bases for how we perceive likable people in pain with those of viewing hateful people in pain. While social bonds are built through sharing the plight and pain of others in the name of empathy, viewing a hateful person in pain also has many potential ramifications. In this functional Magnetic Resonance Imaging (fMRI study, Caucasian Jewish male participants viewed videos of (1 disliked, hateful, anti-Semitic individuals, and (2 liked, non-hateful, tolerant individuals in pain. The results showed that, compared with viewing liked people, viewing hateful people in pain elicited increased responses in regions associated with observation of physical pain (the insular cortex, the anterior cingulate cortex, and the somatosensory cortex, reward processing (the striatum, and frontal regions associated with emotion regulation. Functional connectivity analyses revealed connections between seed regions in the left anterior cingulate cortex and right insular cortex with reward regions, the amygdala, and frontal regions associated with emotion regulation. These data indicate that regions of the brain active while viewing someone in pain may be more active in response to the danger or threat posed by witnessing the pain of a hateful individual more so than the desire to empathize with a likable person’s pain.

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

    Science.gov (United States)

    Yang, Yan-Li; Deng, Hong-Xia; Xing, Gui-Yang; Xia, Xiao-Luan; Li, Hai-Fang

    2015-02-01

    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.

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

    Institute of Scientific and Technical Information of China (English)

    Yan-li Yang; Hong-xia Deng; Gui-yang Xing; Xiao-luan Xia; Hai-fang Li

    2015-01-01

    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 inves-tigated 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, conifrming 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 ifndings 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.

  2. 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.

  3. Loss in Connectivity (LoCo) among regions of the brain reward system in alcohol dependence

    OpenAIRE

    Kuceyeski, Amy; Meyerhoff, Dieter J.; Timothy C. Durazzo; Raj, Ashish

    2012-01-01

    A recently developed measure of structural brain connectivity disruption, the Loss in Connectivity (LoCo), is adapted for studies in alcohol dependence. LoCo uses independent tractography information from young healthy controls to project the location of white matter microstructure abnormalities in alcohol dependent vs. non-dependent individuals onto connected gray matter regions. The LoCo scores are computed from white matter abnormality masks derived at two levels: 1) group-wise differences...

  4. Loss in connectivity among regions of the brain reward system in alcohol dependence

    OpenAIRE

    Kuceyeski, A.; Meyerhoff, DJ; Durazzo, TC; Raj, A.

    2013-01-01

    A recently developed measure of structural brain connectivity disruption, the loss in connectivity (LoCo), is adapted for studies in alcohol dependence. LoCo uses independent tractography information from young healthy controls to project the location of white matter (WM) microstructure abnormalities in alcohol-dependent versus nondependent individuals onto connected gray matter (GM) regions. LoCo scores are computed from WM abnormality masks derived at two levels: (1) groupwise differences o...

  5. 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.

  6. Copper pathology in vulnerable brain regions in Parkinson's disease. : Copper pathology in PD

    OpenAIRE

    Davies, Katherine,; Bohic, Sylvain; Carmona, Asunción; Ortega, Richard; Cottam, Veronica; Hare, Dominic; Finberg, John,; Reyes, Stefanie; Halliday, Glenda; Mercer, Julian; Double, Kay,

    2014-01-01

    International audience; Synchrotron-based x-ray fluorescence microscopy, immunofluorescence, and Western blotting were used to investigate changes in copper (Cu) and Cu-associated pathways in the vulnerable substantia nigra (SN) and locus coeruleus (LC) and in nondegenerating brain regions in cases of Parkinson's disease (PD) and appropriate healthy and disease controls. In PD and incidental Lewy body disease, levels of Cu and Cu transporter protein 1, were significantly reduced in surviving ...

  7. Brain regional differences in CB1 receptor adaptation and regulation of transcription.

    Science.gov (United States)

    Lazenka, M F; Selley, D E; Sim-Selley, L J

    2013-03-19

    Cannabinoid CB1 receptors (CB1Rs) are expressed throughout the brain and mediate the central effects of cannabinoids, including Δ(9)-tetrahydrocannabinol (THC), the main psychoactive constituent of marijuana. Repeated THC administration produces tolerance to cannabinoid-mediated effects, although the magnitude of tolerance varies by effect. Consistent with this observation, CB1R desensitization and downregulation, as well as induction of immediate early genes (IEGs), vary by brain region. Zif268 and c-Fos are induced in the forebrain after acute THC administration. Phosphorylation of the cAMP response-element binding protein (CREB) is increased in a region-specific manner after THC administration. Results differ between acute versus repeated THC injection, and suggest that tolerance to IEG activation might develop in some regions. Repeated THC treatment produces CB1R desensitization and downregulation in the brain, although less adaption occurs in the striatum as compared to regions such as the hippocampus. Repeated THC treatment also induces expression of ΔFosB, a very stable isoform of FosB, in the striatum. Transgenic expression of ∆FosB in the striatum enhances the rewarding effects of several drugs, but its role in THC-mediated effects is not known. The inverse regional relationship between CB1R desensitization and ∆FosB induction suggests that these adaptations might inhibit each other, although this possibility has not been investigated. The differential regional expression of individual IEGs by acute or repeated THC administration suggests that regulation of target genes and effects on CB1R signaling will contribute to the behavioral effects of THC.

  8. Distinct representations of configural and part information across multiple face-selective regions of the human brain

    OpenAIRE

    Golijeh eGolarai; Dara eGhahremani; Eberhardt, Jennifer L.; John D E Gabrieli

    2015-01-01

    Several regions of the human brain respond more strongly to faces than to other visual stimuli, such as regions in the amygdala (AMG), superior temporal sulcus (STS), and the fusiform face area (FFA). It is unclear if these brain regions are similar in representing the configuration or natural appearance of face parts. We used functional magnetic resonance imaging of healthy adults who viewed natural or schematic faces with internal parts that were either normally configured or randomly rearr...

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

    Directory of Open Access Journals (Sweden)

    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.

  10. Changes in the regional homogeneity of resting-state brain activity in minimal hepatic encephalopathy.

    Science.gov (United States)

    Chen, Hua-Jun; Zhu, Xi-Qi; Yang, Ming; Liu, Bin; Zhang, Yi; Wang, Yu; Teng, Gao-Jun

    2012-01-17

    Resting-state functional magnetic resonance imaging (fMRI) has facilitated the study of spontaneous brain activity by measuring low-frequency oscillations in blood-oxygen-level-dependent signals. Analyses of regional homogeneity (ReHo), which reflects the local synchrony of neural activity, have been used to reveal the mechanisms underlying the brain dysfunction in various neuropsychiatric diseases. However, it is not known whether the ReHo is altered in cirrhotic patients with minimal hepatic encephalopathy (MHE). We recruited 18 healthy controls and 18 patients with MHE. The ReHo was calculated to assess the strength of the local signal synchrony. Compared with the healthy controls, the patients with MHE had significantly decreased ReHo in the cuneus and adjacent precuneus, and left inferior parietal lobe, whereas the regions showing increased ReHo in patients with MHE included the left parahippocampal gyrus, right cerebellar vermis, and bilateral anterior cerebellar lobes. We found a positive correlation between the mean ReHo in the cuneus and adjacent precuneus and the score on the digit-symbol test in the patient group. In conclusion, the analysis of the regional homogeneity of resting-state brain activity may provide additional information with respect to a clinical definition of MHE.

  11. 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.

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

    Institute of Scientific and Technical Information of China (English)

    Ping Wu; Lin Chen; Lin Bai; Juan Nie; San Zhang; Yan Xiong; Yu Bai; Can-xin Yin; Fan-rong Liang; Yu-mei Zhou; Fang Zeng; Zheng-jie Li; Lu Luo; Yong-xin Li; Wei Fan; Li-hua Qiu; Wei Qin

    2016-01-01

    Our previous study used regional homogeneity analysis and found that activity in some brain areas of patients with ischemic stroke changed signiifcantly. 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 clin-ical 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 deifciency scale (r = –0.737,P = 0.010). Our ifndings can objectively identify the functional abnormality in some brain regions of ischemic stroke patients.

  13. 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.

  14. Effect of manganese on the concentration of amino acids in different regions of the rat brain.

    Science.gov (United States)

    Lipe, G W; Duhart, H; Newport, G D; Slikker, W; Ali, S F

    1999-01-01

    The present study was designed to determine if chronic exposure of weanlings and adult rats to Mn produces significant alterations in amino acid concentrations in different regions of the rat brain. Weanling (30 day old) and adult (90 day old) male rats were exposed to 10 and 20 mg Mn/kg body weight per day, by gavage, for 30 days. Forty-eight hours after the last dose, animals were sacrificed by decapitation and brains were dissected into different regions to determine the concentration of amino acids by HPLC/EC. A dose dependent decrease in body weight gain was found in the adult, but not in the weanling rats. Significant increases occurred in concentrations of aspartate, glutamate, glutamine, taurine and gamma-aminobutyric acid (GABA) in the cerebellum of the adult rats dosed with 20 mg/kg per day, Mn. A significant decrease in the concentration of glutamine was observed in caudate nucleus and hippocampus of weanling rats dosed with 10 mg/kg, Mn. These data suggest that chronic Mn exposure can produce a decrease in body weight gain in adult rats and alterations in amino acids in different regions of weanling and adult rat brains.

  15. Scrapie strains retain their distinctive characteristics following passages of homogenates from different brain regions and spleen.

    Science.gov (United States)

    Carp, R I; Meeker, H; Sersen, E

    1997-01-01

    The molecular basis of differences among scrapie strains is unknown. The prion theory posits that there are differences in the conformation of the host protease-resistant protein (PrP) molecules and that these differences are responsible for scrapie strains. A corollary of this theory is that the origin of host PrP variation resides in different neuronal cell types. To assess this concept, preparations from three brain regions (cerebrum, cerebellum and olfactory bulb) and from spleen were passaged in C57BL mice by intracerebral injection. After three passages of three scrapie strains in this manner, homogenates of each brain region and spleen were tested for several of the characteristics that distinguish the three strains: (1) the rank order of incubation periods in C57BL mice, (2) induction of obesity in SJL mice and (3) comparative incubation periods in mice with three genotypes for the scrapie incubation period marker. Analysis revealed that virtually all of the criteria that distinguished the three strains prior to passages of the three brain regions and spleen were retained after this series of passages. This finding argues against cellular-based PrP differences providing a basis for strain specificity.

  16. 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.

  17. A defined terminal region of the E. coli chromosome shows late segregation and high FtsK activity.

    Directory of Open Access Journals (Sweden)

    Marie Deghorain

    Full Text Available BACKGROUND: The FtsK DNA-translocase controls the last steps of chromosome segregation in E. coli. It translocates sister chromosomes using the KOPS DNA motifs to orient its activity, and controls the resolution of dimeric forms of sister chromosomes by XerCD-mediated recombination at the dif site and their decatenation by TopoIV. METHODOLOGY: We have used XerCD/dif recombination as a genetic trap to probe the interaction of FtsK with loci located in different regions of the chromosome. This assay revealed that the activity of FtsK is restricted to a ∼400 kb terminal region of the chromosome around the natural position of the dif site. Preferential interaction with this region required the tethering of FtsK to the division septum via its N-terminal domain as well as its translocation activity. However, the KOPS-recognition activity of FtsK was not required. Displacement of replication termination outside the FtsK high activity region had no effect on FtsK activity and deletion of a part of this region was not compensated by its extension to neighbouring regions. By observing the fate of fluorescent-tagged loci of the ter region, we found that segregation of the FtsK high activity region is delayed compared to that of its adjacent regions. SIGNIFICANCE: Our results show that a restricted terminal region of the chromosome is specifically dedicated to the last steps of chromosome segregation and to their coupling with cell division by FtsK.

  18. Vasopressin modulates the activity of catecholamine containing neurons in specific brain regions.

    Science.gov (United States)

    Versteeg, D H; De Kloet, E R; Greidanus, T V; De Wied, D

    1979-01-01

    Following the i.c.v. administration of antivasopressin serum the alpha-MPT-induced disappearance of noradrenaline was decreased in the dorsal septal nucleus, parafascicular nucleus and the rostral part of the nucleus tractus solitarii, whereas that of dopamine was lowered in the caudate nucleus and in the A2 region of the medulla oblongata. In general the effects are opposite to those previously found following the i.c.v. administration of vasopressin. The results support the hypothesis that vasopressin modulates catecholamine neurotransmission in specific brain regions of the rat.

  19. 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.

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

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    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.

  1. Decreased functional connectivity density in pain-related brain regions of female migraine patients without aura.

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    Gao, Qing; Xu, Fei; Jiang, Cui; Chen, Zhifeng; Chen, Huafu; Liao, Huaqiang; Zhao, Ling

    2016-02-01

    Migraine is one of the most prevalent neurological disorders which is suggested to be associated with dysfunctions of the central nervous system. The purpose of the present study was to detect the altered functional connectivity architecture in the large-scale network of the whole brain in migraine without aura (MWoA). Meanwhile, the brain functional hubs which are targeted by MWoA could be identified. A new voxel-based method named functional connectivity density (FCD) mapping was applied to resting-state functional magnetic resonance imaging data of 55 female MWoA patients and 44 age-matched female healthy controls (HC). Comparing to HC, MWoA patients showed abnormal short-range FCD values in bilateral hippocampus, bilateral insula, right amygdale, right anterior cingulate cortex, bilateral putamen, bilateral caudate nucleus and the prefrontal cortex. The results suggested decreased intraregional connectivity of these pain-related brain regions in female MWoA. In addition, short-range FCD values in left prefrontal cortex, putamen and caudate nucleus were significantly negatively correlated with duration of disease in MWoA group, implying the repeated migraine attacks over time may consistently affect the resting-state functional connectivity architecture of these brain hubs. Our findings revealed the dysfunction of brain hubs in female MWoA, and suggested the left prefrontal cortex, putamen and caudate nucleus served as sensitive neuroimaging markers for reflecting the disease duration of female MWoA. This may provide us new insights into the changes in the organization of the large-scale brain network in MWoA.

  2. Food and drug cues activate similar brain regions: a meta-analysis of functional MRI studies.

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    Tang, D W; Fellows, L K; Small, D M; Dagher, A

    2012-06-06

    In healthy individuals, food cues can trigger hunger and feeding behavior. Likewise, smoking cues can trigger craving and relapse in smokers. Brain imaging studies report that structures involved in appetitive behaviors and reward, notably the insula, striatum, amygdala and orbital frontal cortex, tend to be activated by both visual food and smoking cues. Here, by carrying out a meta-analysis of human neuro-imaging studies, we investigate the neural network activated by: 1) food versus neutral cues (14 studies, 142 foci) 2) smoking versus neutral cues (15 studies, 176 foci) 3) smoking versus neutral cues when correlated with craving scores (7 studies, 108 foci). PubMed was used to identify cue-reactivity imaging studies that compared brain response to visual food or smoking cues to neutral cues. Fourteen articles were identified for the food meta-analysis and fifteen articles were identified for the smoking meta-analysis. Six articles were identified for the smoking cue correlated with craving analysis. Meta-analyses were carried out using activation likelihood estimation. Food cues were associated with increased blood oxygen level dependent (BOLD) response in the left amygdala, bilateral insula, bilateral orbital frontal cortex, and striatum. Smoking cues were associated with increased BOLD signal in the same areas, with the exception of the insula. However, the smoking meta-analysis of brain maps correlating cue-reactivity with subjective craving did identify the insula, suggesting that insula activation is only found when craving levels are high. The brain areas identified here are involved in learning, memory and motivation, and their cue-induced activity is an index of the incentive salience of the cues. Using meta-analytic techniques to combine a series of studies, we found that food and smoking cues activate comparable brain networks. There is significant overlap in brain regions responding to conditioned cues associated with natural and drug rewards.

  3. Activation of writing-specific brain regions when reading Chinese as a second language. Effects of training modality and transfer to novel characters.

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    Lagarrigue, Aurélie; Longcamp, Marieke; Anton, Jean Luc; Nazarian, Bruno; Prévot, Laurent; Velay, Jean-Luc; Cao, Fan; Frenck-Mestre, Cheryl

    2017-03-01

    We examined the implication of training modality on the cortical representation of Chinese words in adult second language learners of Chinese. In particular, we tested the implication of the neural substrates of writing in a reading task. The brain network sustaining finger writing was defined neuroanatomically based on an independent functional localizer. We examined the brain activations elicited by Chinese words learned via writing vs. pronunciation, and by novel untrained words, within regions of interest (ROIs) defined according to the position of the activation peaks in the localizer, and at the whole brain level. We revealed activations in the reading task that overlapped with several parts of the finger writing network. In addition, our results provide evidence that the neural substrates of writing are differentially involved in reading depending on the stored knowledge for words, as revealed by the fine-grained response of several regions including the left superior parietal lobule and left precentral gyrus / superior frontal sulcus to the experimental manipulations. Training modality and the linguistic properties of the characters also impacted the response of the left mid-fusiform gyrus, confirming its involvement as the brain region where linguistic, visual and sensorimotor information converge during orthographic processing. At the behavioral level, global handwriting quality during the training sessions was positively correlated to the final translation performance. Our results demonstrate substantial overlap in the neural substrates of reading and writing, and indicate that some regions sustaining handwriting are differentially involved in reading depending on the type of knowledge associated with words. Copyright © 2017 Elsevier Ltd. All rights reserved.

  4. Regional brain signal variability: a novel indicator of pain sensitivity and coping.

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    Rogachov, Anton; Cheng, Joshua C; Erpelding, Nathalie; Hemington, Kasey S; Crawley, Adrian P; Davis, Karen D

    2016-11-01

    Variability in blood oxygen level-dependent (BOLD) functional magnetic resonance imaging (fMRI) signals reflects the moment-by-moment fluctuations in resting-state fMRI (rs-fMRI) activity within specific areas of the brain. Regional BOLD signal variability was recently proposed to serve an important functional role in the efficacy of neural systems because of its relationship to behavioural performance in aging and cognition studies. We previously showed that individuals who better cope with pain have greater fluctuations in interregional functional connectivity, but it is not known whether regional brain signal variability is a mechanism underlying pain coping. We tested the hypothesis that individual pain sensitivity and coping is reflected by regional fMRI BOLD signal variability within dynamic pain connectome-brain systems implicated in the pain experience. We acquired resting-state fMRI and assessed pain threshold, suprathreshold temporal summation of pain, and the impact of pain on cognition in 80 healthy right-handed individuals. We found that regional BOLD signal variability: (1) inversely correlated with an individual's temporal summation of pain within the ascending nociceptive pathway (primary and secondary somatosensory cortex), default mode network, and salience network; (2) was correlated with an individual's ability to cope with pain during a cognitive interference task within the periaqueductal gray, a key opiate-rich brainstem structure for descending pain modulation; and (3) provided information not captured from interregional functional connectivity. Therefore, regional BOLD variability represents a pain metric with potential implications for prediction of chronic pain resilience vs vulnerability.

  5. Modulation of sensitivity to alcohol by cortical and thalamic brain regions.

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    Jaramillo, Anel A; Randall, Patrick A; Frisbee, Suzanne; Besheer, Joyce

    2016-10-01

    The nucleus accumbens core (AcbC) is a key brain region known to regulate the discriminative stimulus/interoceptive effects of alcohol. As such, the goal of the present work was to identify AcbC projection regions that may also modulate sensitivity to alcohol. Accordingly, AcbC afferent projections were identified in behaviorally naïve rats using a retrograde tracer which led to the focus on the medial prefrontal cortex (mPFC), insular cortex (IC) and rhomboid thalamic nucleus (Rh). Next, to examine the possible role of these brain regions in modulating sensitivity to alcohol, neuronal response to alcohol in rats trained to discriminate alcohol (1 g/kg, intragastric [IG]) vs. water was examined using a two-lever drug discrimination task. As such, rats were administered water or alcohol (1 g/kg, IG) and brain tissue was processed for c-Fos immunoreactivity (IR), a marker of neuronal activity. Alcohol decreased c-Fos IR in the mPFC, IC, Rh and AcbC. Lastly, site-specific pharmacological inactivation with muscimol + baclofen (GABAA agonist + GABAB agonist) was used to determine the functional role of the mPFC, IC and Rh in modulating the interoceptive effects of alcohol in rats trained to discriminate alcohol (1 g/kg, IG) vs. water. mPFC inactivation resulted in full substitution for the alcohol training dose, and IC and Rh inactivation produced partial alcohol-like effects, demonstrating the importance of these regions, with known projections to the AcbC, in modulating sensitivity to alcohol. Together, these data demonstrate a site of action of alcohol and the recruitment of cortical/thalamic regions in modulating sensitivity to the interoceptive effects of alcohol.

  6. Gene co-expression analysis identifies brain regions and cell types involved in migraine pathophysiology: a GWAS-based study using the Allen Human Brain Atlas.

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    Eising, Else; Huisman, Sjoerd M H; Mahfouz, Ahmed; Vijfhuizen, Lisanne S; Anttila, Verneri; Winsvold, Bendik S; Kurth, Tobias; Ikram, M Arfan; Freilinger, Tobias; Kaprio, Jaakko; Boomsma, Dorret I; van Duijn, Cornelia M; Järvelin, Marjo-Riitta R; Zwart, John-Anker; Quaye, Lydia; Strachan, David P; Kubisch, Christian; Dichgans, Martin; Davey Smith, George; Stefansson, Kari; Palotie, Aarno; Chasman, Daniel I; Ferrari, Michel D; Terwindt, Gisela M; de Vries, Boukje; Nyholt, Dale R; Lelieveldt, Boudewijn P F; van den Maagdenberg, Arn M J M; Reinders, Marcel J T

    2016-04-01

    Migraine is a common disabling neurovascular brain disorder typically characterised by attacks of severe headache and associated with autonomic and neurological symptoms. Migraine is caused by an interplay of genetic and environmental factors. Genome-wide association studies (GWAS) have identified over a dozen genetic loci associated with migraine. Here, we integrated migraine GWAS data with high-resolution spatial gene expression data of normal adult brains from the Allen Human Brain Atlas to identify specific brain regions and molecular pathways that are possibly involved in migraine pathophysiology. To this end, we used two complementary methods. In GWAS data from 23,285 migraine cases and 95,425 controls, we first studied modules of co-expressed genes that were calculated based on human brain expression data for enrichment of genes that showed association with migraine. Enrichment of a migraine GWAS signal was found for five modules that suggest involvement in migraine pathophysiology of: (i) neurotransmission, protein catabolism and mitochondria in the cortex; (ii) transcription regulation in the cortex and cerebellum; and (iii) oligodendrocytes and mitochondria in subcortical areas. Second, we used the high-confidence genes from the migraine GWAS as a basis to construct local migraine-related co-expression gene networks. Signatures of all brain regions and pathways that were prominent in the first method also surfaced in the second method, thus providing support that these brain regions and pathways are indeed involved in migraine pathophysiology.

  7. SLC9A9 Co-expression modules in autism-associated brain regions.

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    Patak, Jameson; Hess, Jonathan L; Zhang-James, Yanli; Glatt, Stephen J; Faraone, Stephen V

    2016-07-21

    SLC9A9 is a sodium hydrogen exchanger present in the recycling endosome and highly expressed in the brain. It is implicated in neuropsychiatric disorders, including autism spectrum disorders (ASDs). Little research concerning its gene expression patterns and biological pathways has been conducted. We sought to investigate its possible biological roles in autism-associated brain regions throughout development. We conducted a weighted gene co-expression network analysis on RNA-seq data downloaded from Brainspan. We compared prenatal and postnatal gene expression networks for three ASD-associated brain regions known to have high SLC9A9 gene expression. We also performed an ASD-associated single nucleotide polymorphism enrichment analysis and a cell signature enrichment analysis. The modules showed differences in gene constituents (membership), gene number, and connectivity throughout time. SLC9A9 was highly associated with immune system functions, metabolism, apoptosis, endocytosis, and signaling cascades. Gene list comparison with co-immunoprecipitation data was significant for multiple modules. We found a disproportionately high autism risk signal among genes constituting the prenatal hippocampal module. The modules were enriched with astrocyte and oligodendrocyte markers. SLC9A9 is potentially involved in the pathophysiology of ASDs. Our investigation confirmed proposed functions for SLC9A9, such as endocytosis and immune regulation, while also revealing potential roles in mTOR signaling and cell survival.. By providing a concise molecular map and interactions, evidence of cell type and implicated brain regions we hope this will guide future research on SLC9A9. Autism Res 2016. © 2016 International Society for Autism Research, Wiley Periodicals, Inc.

  8. Genomic imprinting variations in the mouse type 3 deiodinase gene between tissues and brain regions.

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    Martinez, M Elena; Charalambous, Marika; Saferali, Aabida; Fiering, Steven; Naumova, Anna K; St Germain, Donald; Ferguson-Smith, Anne C; Hernandez, Arturo

    2014-11-01

    The Dio3 gene, which encodes for the type 3 deiodinase (D3), controls thyroid hormone (TH) availability. The lack of D3 in mice results in tissue overexposure to TH and a broad neuroendocrine phenotype. Dio3 is an imprinted gene, preferentially expressed from the paternally inherited allele in the mouse fetus. However, heterozygous mice with paternal inheritance of the inactivating Dio3 mutation exhibit an attenuated phenotype when compared with that of Dio3 null mice. To investigate this milder phenotype, the allelic expression of Dio3 was evaluated in different mouse tissues. Preferential allelic expression of Dio3 from the paternal allele was observed in fetal tissues and neonatal brain regions, whereas the biallelic Dio3 expression occurred in the developing eye, testes, and cerebellum and in the postnatal brain neocortex, which expresses a larger Dio3 mRNA transcript. The newborn hypothalamus manifests the highest degree of Dio3 expression from the paternal allele, compared with other brain regions, and preferential allelic expression of Dio3 in the brain relaxed in late neonatal life. A methylation analysis of two regulatory regions of the Dio3 imprinted domain revealed modest but significant differences between tissues, but these did not consistently correlate with the observed patterns of Dio3 allelic expression. Deletion of the Dio3 gene and promoter did not result in significant changes in the tissue-specific patterns of Dio3 allelic expression. These results suggest the existence of unidentified epigenetic determinants of tissue-specific Dio3 imprinting. The resulting variation in the Dio3 allelic expression between tissues likely explains the phenotypic variation that results from paternal Dio3 haploinsufficiency.

  9. 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.

  10. Brain regions involved in swallowing: Evidence from stroke patients in a cross-sectional study

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    Shiva Ebrahimian Dehaghani

    2016-01-01

    Full Text Available Background: Limited data available about the mechanisms of dysphagia and areas involving swallow after brain damage; accordingly it is hard to predict which cases are more likely to develop swallowing dysfunction based on the neuroimaging. The aim of this study was to investigate the relationship between brain lesions and dysphagia in a sample of acute conscious stroke patients.Materials and Methods: In a cross-sectional study, 113 acute conscious stroke patients (69 male mean [standard deviation (SD] age 64.37 [15.1], participated in this study. Two neurologists and one radiologist localized brain lesions according to neuroimaging of the patients. Swallowing functions were assessed clinically by an expert speech pathologist with the Mann Assessment of Swallowing Ability (MASA. The association of brain region and swallowing problem was statistically evaluated using Chi-square test. Results: Mean (SD MASA score for the dysphagic patients was 139.61 (29.77. Swallowing problem was significantly more prevalent in the right primary sensory (P = 0.03, right insula (P = 0.005, and right internal capsule (P = 0.05. Conclusion: It may be concluded from these findings that the right hemisphere lesions associated with occurring dysphagia. Further studies using more advanced diagnostic tools on big samples particularly in a perspective structure are needed.

  11. Regional brain shrinkage and change in cognitive performance over two years: The bidirectional influences of the brain and cognitive reserve factors.

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    Persson, Ninni; Ghisletta, Paolo; Dahle, Cheryl L; Bender, Andrew R; Yang, Yiqin; Yuan, Peng; Daugherty, Ana M; Raz, Naftali

    2016-02-01

    We examined relationships between regional brain shrinkage and changes in cognitive performance, while taking into account the influence of chronological age, vascular risk, Apolipoprotein E variant and socioeconomic status. Regional brain volumes and cognitive performance were assessed in 167 healthy adults (age 19-79 at baseline), 90 of whom returned for the follow-up after two years. Brain volumes were measured in six regions of interest (ROIs): lateral prefrontal cortex (LPFC), prefrontal white matter (PFw), hippocampus (Hc), parahippocampal gyrus (PhG), cerebellar hemispheres (CbH), and primary visual cortex (VC), and cognitive performance was evaluated in three domains: episodic memory (EM), fluid intelligence (Gf), and vocabulary (V). Average volume loss was observed in Hc, PhG and CbH, but reliable individual differences were noted in all examined ROIs. Average positive change was observed in EM and V performance but not in Gf scores, yet only the last evidenced individual differences in change. We observed reciprocal influences among neuroanatomical and cognitive variables. Larger brain volumes at baseline predicted greater individual gains in Gf, but differences in LPFC volume change were in part explained by baseline level of cognitive performance. In one region (PFw), individual change in volume was coupled with change in Gf. Larger initial brain volumes did not predict slower shrinkage. The results underscore the complex role of brain maintenance and cognitive reserve in adult development.

  12. Brain region specific pre-synaptic and post-synaptic degeneration are early components of neuropathology in prion disease.

    Directory of Open Access Journals (Sweden)

    Zuzana Šišková

    Full Text Available Synaptic abnormalities, one of the key features of prion disease pathogenesis, gives rise to functional deficits and contributes to the devastating clinical outcome. The synaptic compartment is the first to succumb in several neurodegenerative diseases linked with protein misfolding but the mechanisms underpinning this are poorly defined. In our current study we document that a focal intrahippocampal injection of the mouse-adapted 22L scrapie strain produces a complex, region-specific pathology in the brain. Our findings reveal that early synaptic changes in the stratum radiatum of the hippocampus, identical to those observed with the ME7 strain, occur when 22L strain is introduced into the hippocampus. The pathology was defined by degenerating Type I pre-synaptic elements progressively enveloped by the post-synaptic density of the dendritic spine. In contrast, the pathology in the cerebellum suggested that dendritic disintegration rather than pre-synaptic abnormalities dominate the early degenerative changes associated with the Purkinje cells. Indeed, both of the major synaptic inputs into the cerebellum, which arise from the parallel and climbing fibers, remained intact even at late stage disease. Immunolabeling with pathway selective antibodies reinforced these findings. These observations demonstrate that neuronal vulnerability to pathological protein misfolding is strongly dependent on the structure and function of the target neurons.

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

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    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.

  14. Functional connectivity analysis using whole brain and regional network metrics in MS patients.

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    Chirumamilla, V C; Fleischer, V; Droby, A; Anjum, T; Muthuraman, M; Zipp, F; Groppa, S

    2016-08-01

    In the present study we investigated brain network connectivity differences between patients with relapsing-remitting multiple sclerosis (RRMS) and healthy controls (HC) as derived from functional resonance magnetic imaging (fMRI) using graph theory. Resting state fMRI data of 18 RRMS patients (12 female, mean age ± SD: 42 ± 12.06 years) and 25 HC (8 female, 29.2 ± 5.38 years) were analyzed. In order to obtain information of differences in entire brain network, we focused on both, local and global network connectivity parameters. And the regional connectivity differences were assessed using regional network parameters. RRMS patients presented a significant increase of modularity in comparison to HC, pointing towards a network structure with densely interconnected nodes within one module, while the number of connections with other modules outside decreases. This higher decomposable network favours cost-efficient local information processing and promotes long-range disconnection. In addition, at the regional anatomical level, the network parameters clustering coefficient and local efficiency were increased in the insula, the superior parietal gyrus and the temporal pole. Our study indicates that modularity as derived from fMRI can be seen as a characteristic connectivity feature that is increased in MS patients compared to HC. Furthermore, specific anatomical regions linked to perception, motor function and cognition were mainly involved in the enhanced local information processing.

  15. Characterization of monoaminergic systems in brain regions of prematurely ageing mice.

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    De la Fuente, Monica; Hernanz, Angel; Medina, Sonia; Guayerbas, Noelia; Fernández, Beatriz; Viveros, Maria Paz

    2003-07-01

    We have previously shown that differences in life span among members of Swiss mouse populations appear to be related to their exploration of a T-maze, with a slow exploration ("slow mice") being linked to increased levels of emotionality/anxiety, an impaired immune function and a shorter life span. Thus, we proposed the slow mice as prematurely ageing mice (PAM). We have now compared the monoaminergic systems of the PAM and of the non-prematurely ageing mice (NPAM), in discrete brain regions. PAM had decreased noradrenaline (NA) levels in all the brain regions analysed, whereas the 3-methoxy-4-hydroxyphenyl glycol (MHPG)/NA ratios were not significantly modified. PAM also showed decreased serotonine (5-HT) levels in hypothalamus, striatum and midbrain, as well as increased 5-hydroxyindol-3-acetic acid (5-HIAA)/5-HT ratios in hypothalamus and hippocampus. The dopamine (DA) content was lower in PAM in most regions, whereas the 3,4-dihydroxyphenylacetic acid (DOPAC)/DA and homovanillic acid (HVA)/DA ratios were either increased or unchanged depending on the region analysed. In most cases, the differences between PAM and NPAM involved both sexes. One exception was the hypothalamus where the differences only affected the male mice. The neurochemical alterations found in PAM resemble some changes reported for aged animals and are related with their behavioural features.

  16. 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.

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

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    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.

  18. Action sentences activate sensory motor regions in the brain independently of their status of reality.

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    de Vega, Manuel; León, Inmaculada; Hernández, Juan A; Valdés, Mitchell; Padrón, Iván; Ferstl, Evelyn C

    2014-07-01

    Some studies have reported that understanding concrete action-related words and sentences elicits activations of motor areas in the brain. The present fMRI study goes one step further by testing whether this is also the case for comprehension of nonfactual statements. Three linguistic structures were used (factuals, counterfactuals, and negations), referring either to actions or, as a control condition, to visual events. The results showed that action sentences elicited stronger activations than visual sentences in the SMA, extending to the primary motor area, as well as in regions generally associated with the planning and understanding of actions (left superior temporal gyrus, left and right supramarginal gyri). Also, we found stronger activations for action sentences than for visual sentences in the extrastriate body area, a region involved in the visual processing of human body movements. These action-related effects occurred not only in factuals but also in negations and counterfactuals, suggesting that brain regions involved in action understanding and planning are activated by default even when the actions are described as hypothetical or as not happening. Moreover, some of these regions overlapped with those activated during the observation of action videos, indicating that the act of understanding action language and that of observing real actions share neural networks. These results support the claim that embodied representations of linguistic meaning are important even in abstract linguistic contexts.

  19. Mindfulness practice leads to increases in regional brain gray matter density.

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    Hölzel, Britta K; Carmody, James; Vangel, Mark; Congleton, Christina; Yerramsetti, Sita M; Gard, Tim; Lazar, Sara W

    2011-01-30

    Therapeutic interventions that incorporate training in mindfulness meditation have become increasingly popular, but to date little is known about neural mechanisms associated with these interventions. Mindfulness-Based Stress Reduction (MBSR), one of the most widely used mindfulness training programs, has been reported to produce positive effects on psychological well-being and to ameliorate symptoms of a number of disorders. Here, we report a controlled longitudinal study to investigate pre-post changes in brain gray matter concentration attributable to participation in an MBSR program. Anatomical magnetic resonance (MR) images from 16 healthy, meditation-naïve participants were obtained before and after they underwent the 8-week program. Changes in gray matter concentration were investigated using voxel-based morphometry, and compared with a waiting list control group of 17 individuals. Analyses in a priori regions of interest confirmed increases in gray matter concentration within the left hippocampus. Whole brain analyses identified increases in the posterior cingulate cortex, the temporo-parietal junction, and the cerebellum in the MBSR group compared with the controls. The results suggest that participation in MBSR is associated with changes in gray matter concentration in brain regions involved in learning and memory processes, emotion regulation, self-referential processing, and perspective taking.

  20. Regional and directional anisotropy of apparent diffusion coefficient in rat brain.

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    Hoehn-Berlage, M; Eis, M; Schmitz, B

    1999-02-01

    Quantitative diffusion maps were recorded in normal rat brain. In multi-slice sections covering the whole brain, strong variation of the apparent diffusion coefficient (ADC) was observed depending on slice position at constant gradient direction. Furthermore, a varying difference between apparent diffusion coefficients depending on gradient direction was found, reaching 32% in the cortex of the ventral-most horizontal sections while showing equal ADC on the dorsal cortex side. The regional variation and directional anisotropy of the ADC was not restricted to white matter but was described for both cortical and subcortical brain tissue. From diffusion coefficients along the three major field gradient directions (ADCx, ADCy, ADCz), the average ADC (ADCaverage) was determined from the trace of the diffusion tensor (D) as 653+/-28 microm2/s for parietal cortex and 671+/-32 microm2/s for lateral cortex, independent of position along the sagittal direction. From these observations about the regional diffusion anisotropy, a more stringent protocol for the description of ischemic ADC changes is proposed.

  1. Adaptation of brain regions to habitat complexity: a comparative analysis in bats (Chiroptera).

    Science.gov (United States)

    Safi, Kamran; Dechmann, Dina K N

    2005-01-22

    Vertebrate brains are organized in modules which process information from sensory inputs selectively. Therefore they are probably under different evolutionary pressures. We investigated the impact of environmental influences on specific brain centres in bats. We showed in a phylogenetically independent contrast analysis that the wing area of a species corrected for body size correlated with estimates of habitat complexity. We subsequently compared wing area, as an indirect measure of habitat complexity, with the size of regions associated with hearing, olfaction and spatial memory, while controlling for phylogeny and body mass. The inferior colliculi, the largest sub-cortical auditory centre, showed a strong positive correlation with wing area in echolocating bats. The size of the main olfactory bulb did not increase with wing area, suggesting that the need for olfaction may not increase during the localization of food and orientation in denser habitat. As expected, a larger wing area was linked to a larger hippocampus in all bats. Our results suggest that morphological adaptations related to flight and neuronal capabilities as reflected by the sizes of brain regions coevolved under similar ecological pressures. Thus, habitat complexity presumably influenced and shaped sensory abilities in this mammalian order independently of each other.

  2. Pain facilitation brain regions activated by nalbuphine are revealed by pharmacological fMRI.

    Directory of Open Access Journals (Sweden)

    Robert Gear

    Full Text Available Nalbuphine, an agonist-antagonist kappa-opioid, produces brief analgesia followed by enhanced pain/hyperalgesia in male postsurgical patients. However, it produces profound analgesia without pain enhancement when co-administration with low dose naloxone. To examine the effect of nalbuphine or nalbuphine plus naloxone on activity in brain regions that may explain these differences, we employed pharmacological magnetic resonance imaging (phMRI in a double blind cross-over study with 13 healthy male volunteers. In separate imaging sessions subjects were administered nalbuphine (5 mg/70 kg preceded by either saline (Sal-Nalb or naloxone 0.4 mg (Nalox-Nalb. Blood oxygen level-dependent (BOLD activation maps followed by contrast and connectivity analyses revealed marked differences. Sal-Nalb produced significantly increased activity in 60 brain regions and decreased activity in 9; in contrast, Nalox-Nalb activated only 14 regions and deactivated only 3. Nalbuphine, like morphine in a previous study, attenuated activity in the inferior orbital cortex, and, like noxious stimulation, increased activity in temporal cortex, insula, pulvinar, caudate, and pons. Co-administration/pretreatment of naloxone selectively blocked activity in pulvinar, pons and posterior insula. Nalbuphine induced functional connectivity between caudate and regions in the frontal, occipital, temporal, insular, middle cingulate cortices, and putamen; naloxone co-admistration reduced all connectivity to non-significant levels, and, like phMRI measures of morphine, increased activation in other areas (e.g., putamen. Naloxone pretreatment to nalbuphine produced changes in brain activity possess characteristics of both analgesia and algesia; naloxone selectively blocks activity in areas associated with algesia. Given these findings, we suggest that nalbuphine interacts with a pain salience system, which can modulate perceived pain intensity.

  3. Seasonal and regional differences in gene expression in the brain of a hibernating mammal.

    Directory of Open Access Journals (Sweden)

    Christine Schwartz

    Full Text Available Mammalian hibernation presents a unique opportunity to study naturally occurring neuroprotection. Hibernating ground squirrels undergo rapid and extreme physiological changes in body temperature, oxygen consumption, and heart rate without suffering neurological damage from ischemia and reperfusion injury. Different brain regions show markedly different activity during the torpor/arousal cycle: the cerebral cortex shows activity only during the periodic returns to normothermia, while the hypothalamus is active over the entire temperature range. Therefore, region-specific neuroprotective strategies must exist to permit this compartmentalized spectrum of activity. In this study, we use the Illumina HiSeq platform to compare the transcriptomes of these two brain regions at four collection points across the hibernation season: April Active, October Active, Torpor, and IBA. In the cerebral cortex, 1,085 genes were found to be differentially expressed across collection points, while 1,063 genes were differentially expressed in the hypothalamus. Comparison of these transcripts indicates that the cerebral cortex and hypothalamus implement very different strategies during hibernation, showing less than 20% of these differentially expressed genes in common. The cerebral cortex transcriptome shows evidence of remodeling and plasticity during hibernation, including transcripts for the presynaptic cytomatrix proteins bassoon and piccolo, and extracellular matrix components, including laminins and collagens. Conversely, the hypothalamic transcriptome displays upregulation of transcripts involved in damage response signaling and protein turnover during hibernation, including the DNA damage repair gene RAD50 and ubiquitin E3 ligases UBR1 and UBR5. Additionally, the hypothalamus transcriptome also provides evidence of potential mechanisms underlying the hibernation phenotype, including feeding and satiety signaling, seasonal timing mechanisms, and fuel

  4. 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…

  5. 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…

  6. Regional brain activity change predicts responsiveness to treatment for stuttering in adults.

    Science.gov (United States)

    Ingham, Roger J; Wang, Yuedong; Ingham, Janis C; Bothe, Anne K; Grafton, Scott T

    2013-12-01

    Developmental stuttering is known to be associated with aberrant brain activity, but there is no evidence that this knowledge has benefited stuttering treatment. This study investigated whether brain activity could predict progress during stuttering treatment for 21 dextral adults who stutter (AWS). They received one of two treatment programs that included periodic H2(15)O PET scanning (during oral reading, monologue, and eyes-closed rest conditions). All participants successfully completed an initial treatment phase and then entered a phase designed to transfer treatment gains; 9/21 failed to complete this latter phase. The 12 pass and 9 fail participants were similar on speech and neural system variables before treatment, and similar in speech performance after the initial phase of their treatment. At the end of the initial treatment phase, however, decreased activation within a single region, L. putamen, in all 3 scanning conditions was highly predictive of successful treatment progress.

  7. Brain regions involved in the recognition of happiness and sadness in music.

    Science.gov (United States)

    Khalfa, Stéphanie; Schon, Daniele; Anton, Jean-Luc; Liégeois-Chauvel, Catherine

    2005-12-19

    Here, we used functional magnetic resonance imaging to test for the lateralization of the brain regions specifically involved in the recognition of negatively and positively valenced musical emotions. The manipulation of two major musical features (mode and tempo), resulting in the variation of emotional perception along the happiness-sadness axis, was shown to principally involve subcortical and neocortical brain structures, which are known to intervene in emotion processing in other modalities. In particular, the minor mode (sad excerpts) involved the left orbito and mid-dorsolateral frontal cortex, which does not confirm the valence lateralization model. We also show that the recognition of emotions elicited by variations of the two perceptual determinants rely on both common (BA 9) and distinct neural mechanisms.

  8. Regional variations in the apparent diffusion coefficient and the intracellular distribution of water in rat brain during acute focal ischemia.

    Science.gov (United States)

    Liu, K F; Li, F; Tatlisumak, T; Garcia, J H; Sotak, C H; Fisher, M; Fenstermacher, J D

    2001-08-01

    The apparent diffusion coefficient of water (ADC) rapidly drops in ischemic tissue after cerebral artery occlusion. This acute drop is thought to be caused by the loss of extracellular fluid and the gain of intracellular fluid. To test the latter possibility, changes in ADC and the size of several cellular compartments were assessed in 3 regions of rat brain at the end of 90 minutes of focal cerebral ischemia. One middle cerebral artery was permanently occluded in 8 Sprague-Dawley rats; sham occlusions were performed in 2 other rats. ADC maps were generated 90 minutes later, and the brains were immediately perfusion fixed. Three regions of interest (ROIs) were defined on the basis of ADC range. Various neuronal, astrocytic, and capillary compartments in each ROI were quantified with light and electron microscopy. At the end of 90 minutes of ischemia, mean ADC was normal in the cortex of sham-operated rats and the contralateral cortex of ischemic rats (ROI-a), 25% lower in the ipsilateral frontoparietal cortex (ROI-b), and 45% lower in the ischemic lateral caudoputamen (ROI-c). At this time, the frequency of swollen astrocytic cell bodies and volume of swollen dendrites and astrocytic processes in neuropil were ROI-a

  9. 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)

  10. Combination of nucleic acid and protein isolation with tissue array construction: using defined histologic regions in single frozen tissue blocks for multiple research purposes.

    Science.gov (United States)

    Li, Hong; Sun, Yuan; Kong, Qing-You; Zhang, Kai-Li; Wang, Xiao-Wei; Chen, Xiao-Yan; Wang, Qian; Liu, Jia

    2003-09-01

    Precise dissection of defined histological regions for nucleic acid and protein isolation is a precedent step in finding out cancer-related alterations, and high quality tissue microarrays are demanded in the validation of screened genetic alterations by multiple in situ approaches. In this study, a combined technique was developed by which sample isolation and tissue array construction could be performed on the defined morphological region(s) in single tissue block. The RNA and protein samples generated from the selected portions were of good quality and sufficient for multiple experimental purposes. The frozen tissue arrays constructed on a novel recipient are suitable for multiple in situ evaluations including immunohistochemical staining and mRNA hybridisation. In most cases, the data obtained from in situ assays coincided well with the ones revealed by RT-PCR and Western blot hybridisation. The potential experimental bias caused by cell contamination can be amended by tissue array-based retrospective examination. The combination of tissue-selective sample preparations with tissue array construction thus provide a tool by which comprehensive cancer research can be performed on defined histological regions in a series of single frozen tissue blocks.

  11. A synthetic luciferin improves in vivo bioluminescence imaging of gene expression in cardiovascular brain regions.

    Science.gov (United States)

    Simonyan, Hayk; Hurr, Chansol; Young, Colin N

    2016-10-01

    Bioluminescence imaging is an effective tool for in vivo investigation of molecular processes. We have demonstrated the applicability of bioluminescence imaging to spatiotemporally monitor gene expression in cardioregulatory brain nuclei during the development of cardiovascular disease, via incorporation of firefly luciferase into living animals, combined with exogenous d-luciferin substrate administration. Nevertheless, d-luciferin uptake into the brain tissue is low, which decreases the sensitivity of bioluminescence detection, particularly when considering small changes in gene expression in tiny central areas. Here, we tested the hypothesis that a synthetic luciferin, cyclic alkylaminoluciferin (CycLuc1), would be superior to d-luciferin for in vivo bioluminescence imaging in cardiovascular brain regions. Male C57B1/6 mice underwent targeted delivery of an adenovirus encoding the luciferase gene downstream of the CMV promoter to the subfornical organ (SFO) or paraventricular nucleus of hypothalamus (PVN), two crucial cardioregulatory neural regions. While bioluminescent signals could be obtained following d-luciferin injection (150 mg/kg), CycLuc1 administration resulted in a three- to fourfold greater bioluminescent emission from the SFO and PVN, at 10- to 20-fold lower substrate concentrations (7.5-15 mg/kg). This CycLuc1-mediated enhancement in bioluminescent emission was evident early following substrate administration (i.e., 6-10 min) and persisted for up to 1 h. When the exposure time was reduced from 60 s to 1,500 ms, minimal signal in the PVN was detectable with d-luciferin, whereas bioluminescent images could be reliably captured with CycLuc1. These findings demonstrate that bioluminescent imaging with the synthetic luciferin CycLuc1 provides an improved physiological genomics tool to investigate molecular events in discrete cardioregulatory brain nuclei.

  12. 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.

  13. Individual 3D region-of-interest atlas of the human brain: knowledge-based class image analysis for extraction of anatomical objects

    Science.gov (United States)

    Wagenknecht, Gudrun; Kaiser, Hans-Juergen; Sabri, Osama; Buell, Udalrich

    2000-06-01

    After neural network-based classification of tissue types, the second step of atlas extraction is knowledge-based class image analysis to get anatomically meaningful objects. Basic algorithms are region growing, mathematical morphology operations, and template matching. A special algorithm was designed for each object. The class label of each voxel and the knowledge about the relative position of anatomical objects to each other and to the sagittal midplane of the brain can be utilized for object extraction. User interaction is only necessary to define starting, mid- and end planes for most object extractions and to determine the number of iterations for erosion and dilation operations. Extraction can be done for the following anatomical brain regions: cerebrum; cerebral hemispheres; cerebellum; brain stem; white matter (e.g., centrum semiovale); gray matter [cortex, frontal, parietal, occipital, temporal lobes, cingulum, insula, basal ganglia (nuclei caudati, putamen, thalami)]. For atlas- based quantification of functional data, anatomical objects can be convoluted with the point spread function of functional data to take into account the different resolutions of morphological and functional modalities. This method allows individual atlas extraction from MRI image data of a patient without the need of warping individual data to an anatomical or statistical MRI brain atlas.

  14. Temporal change in regional brain distribution of the technetium-99m ethyl cysteinate dimer

    Energy Technology Data Exchange (ETDEWEB)

    Ueda, Osamu; Ashihara, Tatsuhiko; Wake, Seiji; Tsuru, Masato; Izawa, Ichiro; Takahashi, Ryuji (Himeji Cardiovascular Center, Hyogo (Japan)); Kida, Tohru; Nakade, Takahide

    1993-09-01

    To determine the data acquisition timing on the SPECT of the brain using Technetium-99m ethyl cysteinate dimer ([sup 99m]Tc-ECD), the changes in the brain distribution of the tracer were examined in 10 patients with cerebrovascular disease (CVD) and 4 patients with neurological degenerative disease. Immediately after I.V. administration of [sup 99m]Tc-ECD with a dose of 740 MBq, the dynamic planar images (5 sec/frame x 60 frames) and consecutive early 6 SPECT images (5 sec/view x 64 views each) were obtained. The delayed SPECT images (30 sec/view x 64 views) were taken 3 hr after injection. The following parameters were evaluated: (1) the whole brain time-activity curve of [sup 99m]Tc-ECD; (2) the count of the region of interest (ROI) placed in the frontal lobe, temporal lobe, occipital lobe, parietal lobe, and cerebellum; (3) the count ratio of the lesion to the counterpart of the unaffected side, and to the ipsilateral cerebellum in CVD patients; and (4) the changes in the intra-cranial background and the extra-cranial background, where the former was expressed as the count ratio of the ventricle to gray matter and the latter as the count ratio of the peri-cranial regions to the whole brain. The whole brain time-activity curves of [sup 99m]Tc-ECD demonstrated a rapid raise in the uptake after the tracer injection and a subsequent plateau 3 min after the injection. A washout of [sup 99m]Tc-ECD was minimal in all ROIs during the period on the early 6 SPECT images. The count ratio of the lesion to the normal areas was constant on both early and delayed SPECT images. The intra-cranial background activity was unchanged during the whole periods, while the extra-cranial background activity reduced with time. These results suggested that the data acquisition of brain SPECT with [sup 99m]Tc-ECD could be initiated 5 min after the tracer injection. (author).

  15. Comparative transcriptome analysis in induced neural stem cells reveals defined neural cell identities in vitro and after transplantation into the adult rodent brain.

    Science.gov (United States)

    Hallmann, Anna-Lena; Araúzo-Bravo, Marcos J; Zerfass, Christina; Senner, Volker; Ehrlich, Marc; Psathaki, Olympia E; Han, Dong Wook; Tapia, Natalia; Zaehres, Holm; Schöler, Hans R; Kuhlmann, Tanja; Hargus, Gunnar

    2016-05-01

    Reprogramming technology enables the production of neural progenitor cells (NPCs) from somatic cells by direct transdifferentiation. However, little is known on how neural programs in these induced neural stem cells (iNSCs) differ from those of alternative stem cell populations in vitro and in vivo. Here, we performed transcriptome analyses on murine iNSCs in comparison to brain-derived neural stem cells (NSCs) and pluripotent stem cell-derived NPCs, which revealed distinct global, neural, metabolic and cell cycle-associated marks in these populations. iNSCs carried a hindbrain/posterior cell identity, which could be shifted towards caudal, partially to rostral but not towards ventral fates in vitro. iNSCs survived after transplantation into the rodent brain and exhibited in vivo-characteristics, neural and metabolic programs similar to transplanted NSCs. However, iNSCs vastly retained caudal identities demonstrating cell-autonomy of regional programs in vivo. These data could have significant implications for a variety of in vitro- and in vivo-applications using iNSCs.

  16. Apoptotic markers in cultured fibroblasts correlate with brain metabolites and regional brain volume in antipsychotic-naive first-episode schizophrenia and healthy controls.

    Science.gov (United States)

    Batalla, A; Bargalló, N; Gassó, P; Molina, O; Pareto, D; Mas, S; Roca, J M; Bernardo, M; Lafuente, A; Parellada, E

    2015-08-25

    Cultured fibroblasts from first-episode schizophrenia patients (FES) have shown increased susceptibility to apoptosis, which may be related to glutamate dysfunction and progressive neuroanatomical changes. Here we determine whether apoptotic markers obtained from cultured fibroblasts in FES and controls correlate with changes in brain glutamate and N-acetylaspartate (NAA) and regional brain volumes. Eleven antipsychotic-naive FES and seven age- and gender-matched controls underwent 3-Tesla magnetic resonance imaging scanning. Glutamate plus glutamine (Glx) and NAA levels were measured in the anterior cingulate (AC) and the left thalamus (LT). Hallmarks of apoptotic susceptibility (caspase-3-baseline activity, phosphatidylserine externalization and chromatin condensation) were measured in fibroblast cultures obtained from skin biopsies after inducing apoptosis with staurosporine (STS) at doses of 0.25 and 0.5 μM. Apoptotic biomarkers were correlated to brain metabolites and regional brain volume. FES and controls showed a negative correlation in the AC between Glx levels and percentages of cells with condensed chromatin (CC) after both apoptosis inductions (STS 0.5 μM: r = -0.90; P = 0.001; STS 0.25 μM: r = -0.73; P = 0.003), and between NAA and cells with CC (STS 0.5 μM induction r = -0.76; P = 0.002; STS 0.25 μM r = -0.62; P = 0.01). In addition, we found a negative correlation between percentages of cells with CC and regional brain volume in the right supratemporal cortex and post-central region (STS 0.25 and 0.5 μM; P < 0.05 family-wise error corrected (FWEc)). We reveal for the first time that peripheral markers of apoptotic susceptibility may correlate with brain metabolites, Glx and NAA, and regional brain volume in FES and controls, which is consistent with the neuroprogressive theories around the onset of the schizophrenia illness.

  17. The Acute Phase Response and Soman-Induced Status Epilepticus: Temporal, Regional and Cellular Changes in Rat Brain Cytokine Concentrations

    Science.gov (United States)

    2010-07-22

    Methods: The protein levels of 10 cytokines was quantified using bead multiplex immunoassays in damaged brain regions (i.e., piriform cortex...in the piriform cortex, hippocampus, amygdala and thalamus [5,6]. Excitotoxic neural damage following GD exposure activates a neuroinflammatory...quantified using a multiplex bead immunoassay in brain tissue lysates of SE- injury susceptible regions (i.e., piriform cortex, thalamus and hippocampus

  18. Distinct representations of configural and part information across multiple face- selective regions of the human brain

    Directory of Open Access Journals (Sweden)

    Golijeh eGolarai

    2015-11-01

    Full Text Available Several regions of the human brain respond more strongly to faces than to other visual stimuli, such as regions in the amygdala (AMG, superior temporal sulcus (STS, and the fusiform face area (FFA. It is unclear if these brain regions are similar in representing the configuration or natural appearance of face parts. We used functional magnetic resonance imaging of healthy adults who viewed natural or schematic faces with internal parts that were either normally configured or randomly rearranged. Response amplitudes were reduced in the AMG and STS when subjects viewed stimuli whose configuration of parts were digitally rearranged, suggesting representation of the 1st order configuration of face parts. In contrast, response amplitudes in the FFA showed little modulation whether face parts were rearranged or if the natural face parts were replaced with lines. Instead, FFA responses were reduced only when both configural and part information were reduced, revealing an interaction between these factors, suggesting distinct representation of 1st order face configuration and parts in the AMG and STS vs. the FFA.

  19. Oxytocin receptors in brain cortical regions are reduced in haploinsufficient (+/-) reeler mice.

    Science.gov (United States)

    Liu, Wensheng; Pappas, George D; Carter, C Sue

    2005-06-01

    Both oxytocin (OT) and reelin are particularly significant during development and the absence of either may interfere with normal brain development. In addition, reelin is critical to the development of the GABAergic system and GABA modulates the release of OT. Availability of the reelin haploinsufficient (+/-) reeler mouse (HRM) provides a model for examining the role of reelin in the development of the OT system and especially in the expression of the OT receptor (OTR). In this study we used immunocytochemistry and in situ hybridization in HRM versus wild-type (+/-) mice (WTM) to quantify OTR abundance in regions of the brain cortex. Our findings reveal that the oxytocin receptor (OTR), measured either by immunohistochemistry or in situ hybridization, is significantly lower in HRM. Areas showing significant deficits included the piriform cortex, neocortex, retrosplenial cortex and certain regions of the hippocampus. Both reelin and OT play a role in regulating affect and mood. Down-regulation of reelin has been strongly correlated with schizophrenia and it is proposed that HRM may serve as a model for neural deficits seen in both schizophrenia and autism. We report that HRM show regionally specific reductions in OTRs, especially in cortical areas, which previously have been implicated in social memory and cognitive functions. These findings offer support for the more general hypothesis that down-regulation of reelin, of either genetic or epigenetic origin, through associated reductions in the OTRs, contributes to the deficiencies in social behavior that are characteristic of both schizophrenia and autism.

  20. Neural correlates of envy: Regional homogeneity of resting-state brain activity predicts dispositional envy.

    Science.gov (United States)

    Xiang, Yanhui; Kong, Feng; Wen, Xue; Wu, Qihan; Mo, Lei

    2016-11-15

    Envy differs from common negative emotions across cultures. Although previous studies have explored the neural basis of episodic envy via functional magnetic resonance imaging (fMRI), little is known about the neural processes associated with dispositional envy. In the present study, we used regional homogeneity (ReHo) as an index in resting-state fMRI (rs-fMRI) to identify brain regions involved in individual differences in dispositional envy, as measured by the Dispositional Envy Scale (DES). Results showed that ReHo in the inferior/middle frontal gyrus (IFG/MFG) and dorsomedial prefrontal cortex (DMPFC) positively predicted dispositional envy. Moreover, of all the personality traits measured by the Revised NEO Personality Inventory (NEO-PI-R), only neuroticism was significantly associated with dispositional envy. Furthermore, neuroticism mediated the underlying association between the ReHo of the IFG/MFG and dispositional envy. Hence, to the best of our knowledge, this study provides the first evidence that spontaneous brain activity in multiple regions related to self-evaluation, social perception, and social emotion contributes to dispositional envy. In addition, our findings reveal that neuroticism may play an important role in the cognitive processing of dispositional envy.

  1. 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.

  2. 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

  3. Cbln family proteins promote synapse formation by regulating distinct neurexin signaling pathways in various brain regions.

    Science.gov (United States)

    Matsuda, Keiko; Yuzaki, Michisuke

    2011-04-01

    Cbln1 (a.k.a. precerebellin) is a unique bidirectional synaptic organizer that plays an essential role in the formation and maintenance of excitatory synapses between granule cells and Purkinje cells in the mouse cerebellum. Cbln1 secreted from cerebellar granule cells directly induces presynaptic differentiation and indirectly serves as a postsynaptic organizer by binding to its receptor, the δ2 glutamate receptor. However, it remains unclear how Cbln1 binds to the presynaptic sites and interacts with other synaptic organizers. Furthermore, although Cbln1 and its family members Cbln2 and Cbln4 are expressed in brain regions other than the cerebellum, it is unknown whether they regulate synapse formation in these brain regions. In this study, we showed that Cbln1 and Cbln2, but not Cbln4, specifically bound to its presynaptic receptor -α and β isoforms of neurexin carrying the splice site 4 insert [NRXs(S4+)] - and induced synaptogenesis in cerebellar, hippocampal and cortical neurons in vitro. Cbln1 competed with synaptogenesis mediated by neuroligin 1, which lacks the splice sites A and B, but not leucine-rich repeat transmembrane protein 2, possibly by sharing the presynaptic receptor NRXs(S4+). However, unlike neurexins/neuroligins or neurexins/leucine-rich repeat transmembrane proteins, the interaction between NRX1β(S4+) and Cbln1 was insensitive to extracellular Ca(2+) concentrations. These findings revealed the unique and general roles of Cbln family proteins in mediating the formation and maintenance of synapses not only in the cerebellum but also in various other brain regions.

  4. Regional expression of Pax7 in the brain of Xenopus laevis during embryonic and larval development

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    Sandra eBandín

    2013-12-01

    Full Text Available Pax7 is a member of the highly conserved Pax gene family that is expressed in restricted zones of the central nervous system during development, being involved in early brain regionalization and the maintenance of the regional identity. Using sensitive immunohistochemical techniques we have analyzed the spatiotemporal pattern of Pax7 expression in the brain of the anuran amphibian Xenopus laevis, during development. Pax7 expression was first detected in early embryos in the basal plate of prosomere 3, roof and alar plates of prosomere 1 and mesencephalon, and the alar plate of rhombomere 1. As development proceeded, Pax7 cells were observed in the hypothalamus close to the catecholaminergic population of the mammillary region. In the diencephalon, Pax7 was intensely expressed in a portion of the basal plate of prosomere 3, in the roof plate and in scattered cells of the thalamus in prosomere 2, throughout the roof of prosomere 1, and in the commissural and juxtacommissural domains of the pretectum. In the mesencephalon, Pax7 cells were localized in the optic tectum and, to a lesser extent, in the torus semicircularis. The rostral portion of the alar part of rhombomere 1, including the ventricular layer of the cerebellum, expressed Pax7 and, gradually, some of these dorsal cells were observed to populate ventrally the interpeduncular nucleus and the isthmus (rhombomere 0. Additionally, Pax7 positive cells were found in the ventricular zone of the ventral part of the alar plate along the rhombencephalon and the spinal cord. The findings show that the strongly conserved features of Pax7 expression through development shared by amniote vertebrates are also present in the anamniote amphibians as a common characteristic of the brain organization of tetrapods.

  5. In vivo electroporation to physiologically identified deep brain regions in postnatal mammals.

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    Ohmura, Nami; Kawasaki, Kazuha; Satoh, Takemasa; Hata, Yoshio

    2015-01-01

    Genetic manipulation is widely used to research the central nervous system (CNS). The manipulation of molecular expression in a small number of neurons permits the detailed investigation of the role of specific molecules on the function and morphology of the neurons. Electroporation is a broadly used technique for gene transfer in the CNS. However, the targeting of gene transfer using electroporation in postnatal animals was restricted to the cortex, hippocampus, or the region facing the ventricle in previous reports. Electroporation targeting of deep brain structures, such as the thalamus, has been difficult. We introduce a novel electroporation technique that enables gene transfer to a physiologically identified deep brain region using a glass pipette. We recorded neural activity in young-adult mice to identify the location of the lateral geniculate nucleus (LGN) of the thalamus, using a glass pipette electrode containing the plasmid DNA encoding enhanced green fluorescent protein (EGFP). The location of the LGN was confirmed by monitoring visual responses, and the plasmid solution was pressure-injected into the recording site. Voltage pulses were delivered through the glass pipette electrode. Several EGFP-labeled somata and dendrites were observed in the LGN after a few weeks, and labeled axons were found in the visual cortex. The EGFP-expressing structures were observed in detail sufficient to reconstruct their morphology in three dimensions. We further confirmed the applicability of this technique in cats. This method should be useful for the transfer of various genes into cells in physiologically identified brain regions in rodents and gyrencephalic mammals.

  6. 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

  7. 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

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    Murai, Hiroshi; Hattori, Hideyuki; Matsumoto, Masayuki [Kanazawa Medical Univ., Uchinada, Ishikawa (Japan)

    2001-12-01

    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)

  8. Spatially defined modulation of skin temperature and hand ownership of both hands in patients with unilateral complex regional pain syndrome.

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    Moseley, G Lorimer; Gallace, Alberto; Iannetti, Gian Domenico

    2012-12-01

    Numerous clinical conditions, including complex regional pain syndrome, are characterized by autonomic dysfunctions (e.g. altered thermoregulation, sometimes confined to a single limb), and disrupted cortical representation of the body and the surrounding space. The presence, in patients with complex regional pain syndrome, of a disruption in spatial perception, bodily ownership and thermoregulation led us to hypothesize that impaired spatial perception might result in a spatial-dependent modulation of thermoregulation and bodily ownership over the affected limb. In five experiments involving a total of 23 patients with complex regional pain syndrome of one arm and 10 healthy control subjects, we measured skin temperature of the hand with infrared thermal imaging, before and after experimental periods of either 9 or 10 min each, during which the hand was held on one or the other side of the body midline. Tactile processing was assessed by temporal order judgements of pairs of vibrotactile stimuli, delivered one to each hand. Pain and sense of ownership over the hand were assessed by self-report scales. Across experiments, when kept on its usual side of the body midline, the affected hand was 0.5 ± 0.3°C cooler than the healthy hand (P hand were prioritized over those delivered to the affected hand. Simply crossing both hands over the midline resulted in (i) warming of the affected hand (the affected hand became 0.4 ± 0.3°C warmer than when it was in the uncrossed position; P = 0.01); (ii) cooling of the healthy hand (by 0.3 ± 0.3°C; P = 0.02); and (iii) reversal of the prioritization of tactile processing. When only the affected hand was crossed over the midline, it became warmer (by 0.5 ± 0.3°C; P = 0.01). When only the healthy hand was crossed over the midline, it became cooler (by 0.3 ± 0.3°C; P = 0.01). The temperature change of either hand was positively related to its distance from the body midline (pooled data: r = 0.76, P hand over the body

  9. Patterns of regional brain hypometabolism associated with knowledge of semantic features and categories in alzheimer's disease

    DEFF Research Database (Denmark)

    Zahn, R.; Garrard, P.; Talazko, J.

    2006-01-01

    The study of semantic memory in patients with Alzheimer's disease (AD) has raised important questions about the representation of conceptual knowledge in the human brain. It is still unknown whether semantic memory impairments are caused by localized damage to specialized regions or by diffuse...... properties of nonliving objects. Visual property verification of living objects was significantly correlated with left posterior fusiform gyrus metabolism (Brodmann's area [BA] 37/19). Effects of visual and functional property verification for nonliving objects largely overlapped in the left anterior...

  10. Common and distinct brain regions processing multisensory bodily signals for peripersonal space and body ownership.

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    Grivaz, Petr; Blanke, Olaf; Serino, Andrea

    2017-02-15

    We take the feeling that our body belongs to us for granted. However, recent research has shown that it is possible to alter the subjective sensation of body ownership (BO) by manipulating multisensory bodily inputs. Several frontal and parietal regions are known to specifically process multisensory cues presented close to the body, i.e., within the peripersonal space (PPS). It has been proposed that these PPS fronto-parietal regions also underlie BO. However, most previous studies investigated the brain mechanisms of either BO or of PPS processing separately and by using a variety of paradigms. Here, we conducted an extensive meta-analysis of functional neuroimaging studies to investigate PPS and BO processing in humans in order to: a) assess quantitatively where each one of these functions was individually processed in the brain; b) identify whether and where these processes shared common or engaged distinct brain mechanisms; c) characterize these areas in terms of whole-brain co-activation networks and functions, respectively. We identified (i) a bilateral PPS network including superior parietal, temporo-parietal and ventral premotor regions and (ii) a BO network including posterior parietal cortex (right intraparietal sulcus, IPS; and left IPS and superior parietal lobule, SPL), right ventral premotor cortex, and the left anterior insula. Co-activation maps related to both PPS and BO encompassed largely overlapping fronto-parietal networks, but whereas the PPS network was more frequently associated with sensorimotor tasks, the BO network was rather associated with attention and awareness tasks. Finally, the conjunction analysis showed that (iii) PPS and BO tasks anatomically overlapped only in two clusters located in the left parietal cortex (dorsally at the intersection between the SPL, the IPS and area 2 and ventrally between areas 2 and IPS). Distinct activations were located for PPS at the temporo-parietal junction and for BO in the anterior insula. These

  11. Brain activation regions in schizophrenia patients performing the game piece memory task

    Institute of Scientific and Technical Information of China (English)

    Daxing Wu; Huifang Yin; Lirong Yan; Changlian Tan; Dewen Hu; Shuqiao Yao

    2009-01-01

    BACKGROUND: Go, a traditional Chinese chess-like game, requires many unknown functions of the brain including attention, imaging, problem solving and processing of spatial working memory. To date, it remains uncertain whether the intellectual activities required to play Go are related to the frontal lobe.OBJECTIVE: To investigate various patterns of brain region activity while schizophrenic patients and normal subjects engaged in memorizing piece placement in the Chinese game of Go. Spatial working memory was measured in order to validate whether the prefrontal lobe participates in this memory process.DESIGN, TIME AND SETTING: Non-randomized, concurrent control trial was performed at Second Xiangya Hospital of Central South University, between May and December 2004.PARTICIPANTS: A total of nine Chinese schizophrenic patients with no brain or bodily diseases and not undergoing electroshock treatment, who were in accordance with the DSM-IV criteria for schizophrenia, as well as thirteen healthy staffs and students with matched age, sex, and education were included. Patients and control subjects had no neurological disorders or mental retardation. In addition, all participants were right-handed.METHODS: The cognitive task for functional magnetic resonance imaging was a block design experiment. Both groups were asked to remember the placement of pieces in the Chinese game of Go on a computer screen. A brain activation map was analyzed in SPM99.MAIN OUTCOME MEASURES: Brain responses were compared with regard to activation region size, volume, and asymmetry indices.RESULTS: Compared with the control group, the reaction time was significantly delayed in schizophrenics performing the working memory task (P < 0.05). When performing the tasks, normal subjects showed significant activation of the bilateral dorsolateral prefrontal lobe with left dominance; the asymmetry indices were: frontal lobe, +0.32; temporal lobe, -0.58; parietal lobe, 0.41 ; and occipital lobe, -0.34. On

  12. Regional age-related effects in the monkey brain measured with 1H magnetic resonance spectroscopy.

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    Ronen, Itamar; Fan, Xiaoying; Schettler, Steve; Jain, Sahil; Murray, Donna; Kim, Dae-Shik; Killiany, Ronald; Rosene, Douglas

    2011-06-01

    The rhesus monkey is a useful model for examining age-related effects on the brain, because of the extensive neuroanatomical homology between the monkey and the human brain, the tight control for neurological diseases as well as the possibility of obtaining relevant behavioral data and post-mortem tissue for histological analyses. Here, proton magnetic resonance spectroscopy ((1)H-MRS) was used together with high-resolution anatomical MRI images to carefully assess regional concentrations of brain metabolites in a group of 20 rhesus monkeys. In an anterior volume of interest (VOI) that covered frontal and prefrontal areas, significant positive correlations of myo-inositol and of total creatine concentrations with age were detected, whereas N-acetyl aspartate (NAA) and choline compounds (Cho) were not significantly correlated with age. In an occipito-parietal VOI, all metabolites showed no statistically significant age-dependent trend. Strong correlations were found between NAA concentration and gray matter fraction in the VOIs as well as between choline compounds and white matter fraction.

  13. Exposure of beta-tubulin regions defined by antibodies on an Arabidopsis thaliana microtubule protofilament model and in the cells

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    Sulimenko Tetyana

    2010-02-01

    Full Text Available Abstract Background The function of the cortical microtubules, composed of αβ-tubulin heterodimers, is linked to their organizational state which is subject to spatial and temporal modulation by environmental cues. The role of tubulin posttranslational modifications in these processes is largely unknown. Although antibodies against small tubulin regions represent useful tool for studying molecular configuration of microtubules, data on the exposure of tubulin epitopes on plant microtubules are still limited. Results Using homology modeling we have generated an Arabidopsis thaliana microtubule protofilament model that served for the prediction of surface exposure of five β-tubulin epitopes as well as tyrosine residues. Peptide scans newly disclosed the position of epitopes detected by antibodies 18D6 (β1-10, TUB2.1 (β426-435 and TU-14 (β436-445. Experimental verification of the results by immunofluorescence microscopy revealed that the exposure of epitopes depended on the mode of fixation. Moreover, homology modeling showed that only tyrosines in the C-terminal region of β-tubulins (behind β425 were exposed on the microtubule external side. Immunofluorescence microscopy revealed tyrosine phosphorylation of microtubules in plant cells, implying that β-tubulins could be one of the targets for tyrosine kinases. Conclusions We predicted surface exposure of five β-tubulin epitopes, as well as tyrosine residues, on the surface of A. thaliana microtubule protofilament model, and validated the obtained results by immunofluorescence microscopy on cortical microtubules in cells. The results suggest that prediction of epitope exposure on microtubules by means of homology modeling combined with site-directed antibodies can contribute to a better understanding of the interactions of plant microtubules with associated proteins.

  14. Label retaining cells (LRCs with myoepithelial characteristic from the proximal acinar region define stem cells in the sweat gland.

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    Yvonne Leung

    Full Text Available Slow cycling is a common feature shared among several stem cells (SCs identified in adult tissues including hair follicle and cornea. Recently, existence of unipotent SCs in basal and lumenal layers of sweat gland (SG has been described and label retaining cells (LRCs have also been localized in SGs; however, whether these LRCs possess SCs characteristic has not been investigated further. Here, we used a H2BGFP LRCs system for in vivo detection of infrequently dividing cells. This system allowed us to specifically localize and isolate SCs with label-retention and myoepithelial characteristics restricted to the SG proximal acinar region. Using an alternative genetic approach, we demonstrated that SG LRCs expressed keratin 15 (K15 in the acinar region and lineage tracing determined that K15 labeled cells contributed long term to the SG structure but not to epidermal homeostasis. Surprisingly, wound healing experiments did not activate proximal acinar SG cells to participate in epidermal healing. Instead, predominantly non-LRCs in the SG duct actively divided, whereas the majority of SG LRCs remained quiescent. However, when we further challenged the system under more favorable isolated wound healing conditions, we were able to trigger normally quiescent acinar LRCs to trans-differentiate into the epidermis and adopt its long term fate. In addition, dissociated SG cells were able to regenerate SGs and, surprisingly, hair follicles demonstrating their in vivo plasticity. By determining the gene expression profile of isolated SG LRCs and non-LRCs in vivo, we identified several Bone Morphogenetic Protein (BMP pathway genes to be up-regulated and confirmed a functional requirement for BMP receptor 1A (BMPR1A-mediated signaling in SG formation. Our data highlight the existence of SG stem cells (SGSCs and their primary importance in SG homeostasis. It also emphasizes SGSCs as an alternative source of cells in wound healing and their plasticity for

  15. HPeak: an HMM-based algorithm for defining read-enriched regions in ChIP-Seq data

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    Maher Christopher A

    2010-07-01

    Full Text Available Abstract Background Protein-DNA interaction constitutes a basic mechanism for the genetic regulation of target gene expression. Deciphering this mechanism has been a daunting task due to the difficulty in characterizing protein-bound DNA on a large scale. A powerful technique has recently emerged that couples chromatin immunoprecipitation (ChIP with next-generation sequencing, (ChIP-Seq. This technique provides a direct survey of the cistrom of transcription factors and other chromatin-associated proteins. In order to realize the full potential of this technique, increasingly sophisticated statistical algorithms have been developed to analyze the massive amount of data generated by this method. Results Here we introduce HPeak, a Hidden Markov model (HMM-based Peak-finding algorithm for analyzing ChIP-Seq data to identify protein-interacting genomic regions. In contrast to the majority of available ChIP-Seq analysis software packages, HPeak is a model-based approach allowing for rigorous statistical inference. This approach enables HPeak to accurately infer genomic regions enriched with sequence reads by assuming realistic probability distributions, in conjunction with a novel weighting scheme on the sequencing read coverage. Conclusions Using biologically relevant data collections, we found that HPeak showed a higher prevalence of the expected transcription factor binding motifs in ChIP-enriched sequences relative to the control sequences when compared to other currently available ChIP-Seq analysis approaches. Additionally, in comparison to the ChIP-chip assay, ChIP-Seq provides higher resolution along with improved sensitivity and specificity of binding site detection. Additional file and the HPeak program are freely available at http://www.sph.umich.edu/csg/qin/HPeak.

  16. Defining differentially methylated regions specific for the acquisition of pluripotency and maintenance in human pluripotent stem cells via microarray.

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    WenYin He

    Full Text Available Epigenetic regulation is critical for the maintenance of human pluripotent stem cells. It has been shown that pluripotent stem cells, such as embryonic stem cells and induced pluripotent stem cells, appear to have a hypermethylated status compared with differentiated cells. However, the epigenetic differences in genes that maintain stemness and regulate reprogramming between embryonic stem cells and induced pluripotent stem cells remain unclear. Additionally, differential methylation patterns of induced pluripotent stem cells generated using diverse methods require further study.Here, we determined the DNA methylation profiles of 10 human cell lines, including 2 ESC lines, 4 virally derived iPSC lines, 2 episomally derived iPSC lines, and the 2 parental cell lines from which the iPSCs were derived using Illumina's Infinium HumanMethylation450 BeadChip. The iPSCs exhibited a hypermethylation status similar to that of ESCs but with distinct differences from the parental cells. Genes with a common methylation pattern between iPSCs and ESCs were classified as critical factors for stemness, whereas differences between iPSCs and ESCs suggested that iPSCs partly retained the parental characteristics and gained de novo methylation aberrances during cellular reprogramming. No significant differences were identified between virally and episomally derived iPSCs. This study determined in detail the de novo differential methylation signatures of particular stem cell lines.This study describes the DNA methylation profiles of human iPSCs generated using both viral and episomal methods, the corresponding somatic cells, and hESCs. Series of ss-DMRs and ES-iPS-DMRs were defined with high resolution. Knowledge of this type of epigenetic information could be used as a signature for stemness and self-renewal and provides a potential method for selecting optimal pluripotent stem cells for human regenerative medicine.

  17. Alkali metals levels in the human brain tissue: Anatomical region differences and age-related changes.

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    Ramos, Patrícia; Santos, Agostinho; Pinto, Edgar; Pinto, Nair Rosas; Mendes, Ricardo; Magalhães, Teresa; Almeida, Agostinho

    2016-12-01

    The link between trace elements imbalances (both "toxic" and "essential") in the human brain and neurodegenerative disease has been subject of extensive research. More recently, some studies have highlighted the potential role of the homeostasis deregulation of alkali metals in specific brain regions as key factor in the pathogenesis of neurodegenerative diseases such as multiple sclerosis and Alzheimer's disease. Using flame atomic emission spectrometry and inductively coupled plasma-mass spectrometry after microwave-assisted acid digestion of the samples, alkali metals (Na, K, Li, Rb and Cs) were determined in 14 different areas of the human brain (frontal cortex, superior and middle temporal gyri, caudate nucleus, putamen, globus pallidus, cingulated gyrus, hippocampus, inferior parietal lobule, visual cortex of the occipital lobe, midbrain, pons, medulla and cerebellum) of adult individuals (n=42; 71±12, range: 50-101 years old) with no known history and evidence of neurodegenerative, neurological or psychiatric disorder. Potassium was found as the most abundant alkali metal, followed by Na, Rb, Cs and Li. Lithium, K and Cs distribution showed to be quite heterogeneous. On the contrary, Rb and Na appeared quite homogeneously distributed within the human brain tissue. The lowest levels of Na, K, Rb and Li were found in the brainstem (midbrain, medulla and pons) and cerebellum, while the lowest levels of Cs were found in the frontal cortex. The highest levels of K (mean±sd; range 15.5±2.5; 8.9-21.8mg/g) Rb (17.2±6.1; 3.9-32.4μg/g and Cs (83.4±48.6; 17.3-220.5ng/g) were found in putamen. The highest levels of Na and Li were found in the frontal cortex (11.6±2.4; 6.6-17.1mg/g) and caudate nucleus (7.6±4.6 2.2-21.3ng/g), respectively. Although K, Cs and Li levels appear to remain largely unchanged with age, some age-related changes were observed for Na and Rb levels in particular brain regions (namely in the hippocampus). Copyright © 2016 Elsevier GmbH. All

  18. Automatic segmentation of meningioma from non-contrasted brain MRI integrating fuzzy clustering and region growing

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    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

  19. Region-specific tauopathy and synucleinopathy in brain of the alpha-synuclein overexpressing mouse model of Parkinson's disease

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    Masliah Eliezer

    2011-08-01

    Full Text Available Abstract Background α-synuclein [α-Syn]-mediated activation of GSK-3β leading to increases in hyperphosphorylated Tau has been shown by us to occur in striata of Parkinson's diseased [PD] patients and in animal models of PD. In Alzheimer's disease, tauopathy exists in several brain regions; however, the pattern of distribution of tauopathy in other brain regions of PD or in animal models of PD is not known. The current studies were undertaken to analyze the distribution of tauopathy in different brain regions in a widely used mouse model of PD, the α-Syn overexpressing mouse. Results High levels of α-Syn levels were seen in the brain stem, with a much smaller increase in the frontal cortex; neither cerebellum nor hippocampus showed any overexpression of α-Syn. Elevated levels of p-Tau, hyperphosphorylated at Ser202, Ser262 and Ser396/404, were seen in brain stem, with lower levels seen in hippocampus. In both frontal cortex and cerebellum, increases were seen only in p-Ser396/404 Tau, but not in p-Ser202 and p-Ser262. p-GSK-3β levels were not elevated in any of the brain regions, although total GSK-3β was elevated in brain stem. p-p38MAPK levels were unchanged in all brain regions examined, while p-ERK levels were elevated in brain stem, hippocampus and cerebellum, but not the frontal cortex. p-JNK levels were increased in brain stem and cerebellum but not in the frontal cortex or hippocampus. Elevated levels of free tubulin, indicating microtubule destabilization, were seen only in the brain stem. Conclusion Our combined data suggest that in this animal model of PD, tauopathy, along with microtubule destabilization, exists primarily in the brain stem and striatum, which are also the two major brain regions known to express high levels of α-Syn and undergo the highest levels of degeneration in human PD. Thus, tauopathy in PD may have a very restricted pattern of distribution.

  20. 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

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

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    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

  2. 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.

  3. 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.

  4. Regional expression of aquaporin 1, 4, and 9 in the brain during pregnancy.

    Science.gov (United States)

    Wiegman, Marchien J; Bullinger, Lisa V; Kohlmeyer, Meghan M; Hunter, Timothy C; Cipolla, Marilyn J

    2008-05-01

    Pregnancy is a state of physiologic adaptation, with significant changes in cardiovascular, renal, and hemodynamic systems. Aquaporins (AQPs) may play a role in facilitating these changes. While AQP expression has been assessed in several organs during pregnancy, little is known about its expression in the brain during pregnancy. Therefore, this study assesses the regional expression of AQP1, 4, and 9 during pregnancy and the postpartum period using real-time quantitative polymerase chain reaction. The authors show that AQP1, 4, and 9 are expressed in the anterior and posterior cerebrum, cerebellum, and brainstem of nonpregnant, midpregnant, late pregnant, and postpartum rats. The regional distribution pattern of AQP4 and 9 remained similar during gestation, whereas this pattern changed for AQP1. The expression levels of AQP1, 4, and 9 in the brainstem did not change with gestation, whereas changes were found in the anterior cerebrum for AQP4 and in the posterior cerebrum and cerebellum for all AQPs.

  5. Selective vulnerability of Rich Club brain regions is an organizational principle of structural connectivity loss in Huntington's disease.

    Science.gov (United States)

    McColgan, Peter; Seunarine, Kiran K; Razi, Adeel; Cole, James H; Gregory, Sarah; Durr, Alexandra; Roos, Raymund A C; Stout, Julie C; Landwehrmeyer, Bernhard; Scahill, Rachael I; Clark, Chris A; Rees, Geraint; Tabrizi, Sarah J

    2015-11-01

    Huntington's disease can be predicted many years before symptom onset, and thus makes an ideal model for studying the earliest mechanisms of neurodegeneration. Diffuse patterns of structural connectivity loss occur in the basal ganglia and cortex early in the disease. However, the organizational principles that underlie these changes are unclear. By understanding such principles we can gain insight into the link between the cellular pathology caused by mutant huntingtin and its downstream effect at the macroscopic level. The 'rich club' is a pattern of organization established in healthy human brains, where specific hub 'rich club' brain regions are more highly connected to each other than other brain regions. We hypothesized that selective loss of rich club connectivity might represent an organizing principle underlying the distributed pattern of structural connectivity loss seen in Huntington's disease. To test this hypothesis we performed diffusion tractography and graph theoretical analysis in a pseudo-longitudinal study of 50 premanifest and 38 manifest Huntington's disease participants compared with 47 healthy controls. Consistent with our hypothesis we found that structural connectivity loss selectively affected rich club brain regions in premanifest and manifest Huntington's disease participants compared with controls. We found progressive network changes across controls, premanifest Huntington's disease and manifest Huntington's disease characterized by increased network segregation in the premanifest stage and loss of network integration in manifest disease. These regional and whole brain network differences were highly correlated with cognitive and motor deficits suggesting they have pathophysiological relevance. We also observed greater reductions in the connectivity of brain regions that have higher network traffic and lower clustering of neighbouring regions. This provides a potential mechanism that results in a characteristic pattern of structural

  6. Regionally-defined niche-breadth of tropical African freshwater plant species predicts their global latitudinal range

    Science.gov (United States)

    Kennedy, Michael; Lang, Pauline; Tapia-Grimaldo, Julissa; Varandas-Martins, Sara; Bruce, Allanah; Moore, Isabel; Sichingabula, Henry; Bottino, Flávia; Murphy, Kevin

    2016-04-01

    This study tested the hypothesis that the measured niche-breadth of river plant species (macrophytes) occurring within a closely-defined geographical area in southern tropical Africa (Zambia), may predict the larger-scale biogeographical range of these species. Two measures of niche-breadth were calculated for 44 riverine macrophyte species commonly occurring in Zambia, using an approach based on PCA ordination with bio-physico-chemical ordination input variables: altitude, stream order, stream flow, pH, conductivity, soluble reactive phosphate concentration (SRP), benthic macroinvertebrate Average Score per Taxon (ASPT), and individual abundance of nine benthic macroinvertebrate families showing differing water quality tolerance, as indicated by their Sensitivity Weightings within the Zambian Invertebrate Scoring System (ZISS). Macrophyte large-scale latitudinal range was derived from world geopositional records held by online databases, supplemented by records held by the authors. The two niche-breadth metrics divided the species into narrow-niche and intermediate/broad-niche categories, showing significant variation in altitude, stream flow, conductivity, SRP and ASPT, but not stream order or pH. There was no evidence to suggest that macrophyte alpha-diversity (as a measure of number of individual niches that may co-exist in a given habitat) showed any significant relationship with individual species niche-breadth. However, macrophyte alpha-diversity was significantly positively correlated with altitude, and significantly negatively related to conductivity, pH, ASPT, SRP, stream flow, and stream order. Narrow-niche macrophyte species included a higher proportion of Afrotropical endemics than did species with broader niche size. There were significant predictive relationships between macrophyte niche breadth and latitudinal range of the target species at global and Afrotropical scales, but not for the Neotropical range of species which occurred in both the

  7. Regional brain volume differences in symptomatic and presymptomatic carriers of familial Alzheimer’s disease mutations

    Science.gov (United States)

    Lee, Grace J; Lu, Po H; Medina, Luis D; Rodriguez-Agudelo, Yaneth; Melchor, Stephanie; Coppola, Giovanni; Braskie, Meredith N; Hua, Xue; Apostolova, Liana G; Leow, Alex D; Thompson, Paul M; Ringman, John M

    2013-01-01

    Background Mutations in the presenilin (PSEN1, PSEN2) and amyloid precursor protein (APP) genes cause familial Alzheimer’s disease (FAD) in a nearly fully penetrant, autosomal dominant manner, providing a unique opportunity to study presymptomatic individuals who can be predicted to develop Alzheimer’s disease (AD) with essentially 100% certainty. Using tensor-based morphometry (TBM), we examined brain volume differences between presymptomatic and symptomatic FAD mutation carriers and non-carrier (NC) relatives. Methods Twenty-five mutation carriers and 10 NC relatives underwent brain MRI and clinical assessment. Four mutation carriers had dementia (MUT-Dem), 12 had amnestic mild cognitive impairment (MUT-aMCI) and nine were cognitively normal (MUT-Norm). TBM brain volume maps of MUT-Norm, MUT-aMCI and MUT-Dem subjects were compared to NC subjects. Results MUT-Norm subjects exhibited significantly smaller volumes in the thalamus, caudate and putamen. MUT-aMCI subjects had smaller volumes in the thalamus, splenium and pons, but not in the caudate or putamen. MUT-Dem subjects demonstrated smaller volumes in temporal, parietal and left frontal regions. As non-demented carriers approached the expected age of dementia diagnosis, this was associated with larger ventricular and caudate volumes and a trend towards smaller temporal lobe volume. Conclusions Cognitively intact FAD mutation carriers had lower thalamic, caudate and putamen volumes, and we found preliminary evidence for increasing caudate size during the predementia stage. These regions may be affected earliest during prodromal stages of FAD, while cortical atrophy may occur in later stages, when carriers show cognitive deficits. Further studies of this population will help us understand the progression of neurobiological changes in AD. PMID:23085935

  8. Social Support Modulates Stress-Related Gene Expression in Various Brain Regions of Piglets

    Science.gov (United States)

    Kanitz, Ellen; Hameister, Theresa; Tuchscherer, Armin; Tuchscherer, Margret; Puppe, Birger

    2016-01-01

    The presence of an affiliative conspecific may alleviate an individual’s stress response in threatening conditions. However, the mechanisms and neural circuitry underlying the process of social buffering have not yet been elucidated. Using the domestic pig as an animal model, we examined the effect of a 4-h maternal and littermate deprivation on stress hormones and on mRNA expression of the glucocorticoid receptor (GR), mineralocorticoid receptor (MR), 11ß-hydroxysteroid dehydrogenase (11ß-HSD) types 1 and 2 and the immediate early gene c-fos in various brain regions of 7-, 21- and 35-day old piglets. The deprivation occurred either alone or with a familiar or unfamiliar age-matched piglet. Compared to piglets deprived alone, the presence of a conspecific animal significantly reduced free plasma cortisol concentrations and altered the MR/GR balance and 11ß-HSD2 and c-fos mRNA expression in the prefrontal cortex (PFC), amygdala and hypothalamus, but not in the hippocampus. The alterations in brain mRNA expression were particularly found in 21- or 35-day old piglets, which may reflect the species-specific postnatal ontogeny of the investigated brain regions. The buffering effects of social support were most pronounced in the amygdala, indicating its significance both for the assessment of social conspecifics as biologically relevant stimuli and for the processing of emotional states. In conclusion, the present findings provide further evidence for the importance of the cortico-limbic network underlying the abilities of individuals to cope with social stress and strongly emphasize the benefits of social partners in livestock with respect to positive welfare and health. PMID:27965550

  9. 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.

  10. Coping with Sleep Deprivation: Shifts in Regional Brain Activity and Learning Strategy

    Science.gov (United States)

    Hagewoud, Roelina; Havekes, Robbert; Tiba, Paula A.; Novati, Arianna; Hogenelst, Koen; Weinreder, Pim; Van der Zee, Eddy A.; Meerlo, Peter

    2010-01-01

    Study Objectives: Dissociable cognitive strategies are used for place navigation. Spatial strategies rely on the hippocampus, an area important for flexible integration of novel information. Response strategies are more rigid and involve the dorsal striatum. These memory systems can compensate for each other in case of temporal or permanent damage. Sleep deprivation has adverse effects on hippocampal function. However, whether the striatal memory system can compensate for sleep-deprivation–induced hippocampal impairments is unknown. Design: With a symmetrical maze paradigm for mice, we examined the effect of sleep deprivation on learning the location of a food reward (training) and on learning that a previously nonrewarded arm was now rewarded (reversal training). Measurements and Results: Five hours of sleep deprivation after each daily training session did not affect performance during training. However, in contrast with controls, sleep-deprived mice avoided a hippocampus-dependent spatial strategy and preferentially used a striatum-dependent response strategy. In line with this, the training-induced increase in phosphorylation of the transcription factor cAMP response-element binding protein (CREB) shifted from hippocampus to dorsal striatum. Importantly, although sleep-deprived mice performed well during training, performance during reversal training was attenuated, most likely due to rigidity of the striatal system they used. Conclusions: Together, these findings suggest that the brain compensates for negative effects of sleep deprivation on the hippocampal memory system by promoting the use of a striatal memory system. However, effects of sleep deprivation can still appear later on because the alternative learning mechanisms and brain regions involved may result in reduced flexibility under conditions requiring adaptation of previously formed memories. Citation: Hagewoud R; Havekes R; Tiba PA; Novati A; Hogenelst K; Weinreder P; Van der Zee EA; Meerlo P

  11. Dose to craniofacial region through portal imaging of pediatric brain tumors.

    Science.gov (United States)

    Hitchen, Christine J; Osa, Etin-Osa; Dewyngaert, J Keith; Chang, Jenghwa; Narayana, Ashwatha

    2012-01-05

    The purpose of this study was to determine dose to the planning target volume (PTV) and organs at risk (OARs) from portal imaging (PI) of the craniofacial region in pediatric brain tumor patients treated with intensity-modulated radiation therapy (IMRT). Twenty pediatric brain tumor patients were retrospectively studied. Each received portal imaging of treatment fields and orthogonal setup fields in the craniofacial region. The number of PI and monitor units used for PI were documented for each patient. Dose distributions and dose-volume histograms were generated to quantify the maximum, minimum, and mean dose to the PTV, and the mean dose to OARs through PI acquisition. The doses resulting from PI are reported as percentage of prescribed dose. The average maximum, minimum, and mean doses to PTV from PI were 2.9 ± 0.7%, 2.2 ± 1.0%, and 2.5 ± 0.7%, respectively. The mean dose to the OARs from PI were brainstem 2.8 ± 1.1%, optic nerves/chiasm 2.6 ± 0.9%, cochlea 2.6 ± 0.9%, hypothalamus/pituitary 2.4 ± 0.6%, temporal lobes 2.3 ± 0.6%, thyroid 1.6 ± 0.8%, and eyes 2.6 ± 0.9%. The mean number of portal images and the mean number of PI monitor units per patient were 58.8 and 173.3, respectively. The dose from PI while treating pediatric brain tumors using IMRT is significant (2%-3% of the prescribed dose). This may result in exceeding the tolerance limit of many critical structures and lead to unwanted late complications and secondary malignancies. Dose contributions from PI should be considered in the final documented dose. Attempts must be made in PI practices to lower the imaging dose when feasible.

  12. Regional changes in glucose metabolism during brain development from the age of 6 years.

    Science.gov (United States)

    Van Bogaert, P; Wikler, D; Damhaut, P; Szliwowski, H B; Goldman, S

    1998-07-01

    Positron emission tomography (PET) with [18F]fluorodeoxyglucose (FDG) studies of 42 subjects ages 6 to 38 years were analyzed using statistical parametric mapping to identify age-related changes in regional distribution of glucose metabolism adjusted for global activity. Whereas adults were normal volunteers, children had idiopathic epilepsy. We studied polynomial expansions of age to identify nonlinear effects and found that adjusted glucose metabolism varied very significantly in the thalamus and the anterior cingulate cortex and to a lesser degree in the basal ganglia, the mesencephalon, and the insular, posterior cingulate, frontal, and postcentral cortices. Regression plots slowed that the best fit was not linear: adjusted glucose metabolism increased mainly before the age of 25 years and then remained relatively stable. Effects persisted when anti-epileptic drug intake and sleep during the FDG uptake were considered as confounding covariates. To determine if the metabolic changes observed were not due to the epileptic condition of the children, PET data obtained in adults with temporal lobe epilepsy were compared with those in our group of normal adult subjects, resulting in the absence of mapping in the age-related regions. This study suggests that brain maturation from the age of 6 years gives rise to a relative increase of synaptic activities in the thalamus, possibly as a consequence of improved corticothalamic connections. Increased metabolic activity in the anterior cingulate cortex is probably related to these thalamic changes and suggests that the limbic system is involved in the processes of brain maturation.

  13. Effects of endotoxin and tumor necrosis factor alpha on regional brain neurotransmitters in mice.

    Science.gov (United States)

    Cho, L; Tsunoda, M; Sharma, R P

    1999-01-01

    Alterations in regional brain concentration of dopamine (DA), norepinephrine (NE), serotonin (5-HT) and their metabolites were investigated in male BALB/c mice injected intraperitoneally with bacterial lipopolysaccharide (LPS, 2 mg kg(-1)) or recombinant murine tumor necrosis factor alpha (TNFalpha, 0.1 mg kg(-1)) at 2, 6, 12 and 24 h after the injection. At 2 h post-injection the LPS administration resulted in hypothermia, which was not apparent at later time points. No consistent effects were observed by either LPS or TNFalpha on peripheral leukocyte counts or plasma transaminase levels. Both LPS and TNFalpha slightly elevated NE metabolism in the striatum at 2-12 h. Concentrations of DA and its metabolites were significantly elevated only in the hypothalamus following TNFalpha at 24 h. Tumor necrosis factor alpha exerted pronounced effects on 5-HT metabolism in most brain regions at 2 h. Results suggest that the effect of LPS is more complex compared with TNFalpha because of the endogenous production of other cytokines including the TNFalpha.

  14. 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.

  15. Inversion of Gravity Data to Define the Pre-Cenozoic Surface and Regional Structures Possibly Influencing Groundwater Flow in the Rainier Mesa Region, Nye County, Nevada

    Science.gov (United States)

    Hildenbrand, Thomas G.; Phelps, Geoffrey A.; Mankinen, Edward A.

    2006-01-01

    A three-dimensional inversion of gravity data from the Rainier Mesa area and surrounding regions reveals a topographically complex pre-Cenozoic basement surface. This model of the depth to pre-Cenozoic basement rocks is intended for use in a 3D hydrogeologic model being constructed for the Rainier Mesa area. Prior to this study, our knowledge of the depth to pre-Cenozoic basement rocks was based on a regional model, applicable to general studies of the greater Nevada Test Site area but inappropriate for higher resolution modeling of ground-water flow across the Rainier Mesa area. The new model incorporates several changes that lead to significant improvements over the previous regional view. First, the addition of constraining wells, encountering old volcanic rocks lying above but near pre-Cenozoic basement, prevents modeled basement from being too shallow. Second, an extensive literature and well data search has led to an increased understanding of the change of rock density with depth in the vicinity of Rainier Mesa. The third, and most important change, relates to the application of several depth-density relationships in the study area instead of a single generalized relationship, thereby improving the overall model fit. In general, the pre-Cenozoic basement surface deepens in the western part of the study area, delineating collapses within the Silent Canyon and Timber Mountain caldera complexes, and shallows in the east in the Eleana Range and Yucca Flat regions, where basement crops out. In the Rainier Mesa study area, basement is generally shallow (model identifies previously unrecognized structures within the pre-Cenozoic basement that may influence ground-water flow, such as a shallow basement ridge related to an inferred fault extending northward from Rainier Mesa into Kawich Valley.

  16. Inversion of Gravity Data to Define the Pre-Cenozoic Surface and Regional Structures Possibly Influencing Groundwater Flow in the Rainier Mesa Region, Nye County, Nevada.

    Energy Technology Data Exchange (ETDEWEB)

    Thomas G. Hildenbrand; Geoffrey A. Phelps; Edward A. Mankinen

    2006-09-21

    A three-dimensional inversion of gravity data from the Rainier Mesa area and surrounding regions reveals a topographically complex pre-Cenozoic basement surface. This model of the depth to pre-Cenozoic basement rocks is intended for use in a 3D hydrogeologic model being constructed for the Rainier Mesa area. Prior to this study, our knowledge of the depth to pre-Cenozoic basement rocks was based on a regional model, applicable to general studies of the greater Nevada Test Site area but inappropriate for higher resolution modeling of ground-water flow across the Rainier Mesa area. The new model incorporates several changes that lead to significant improvements over the previous regional view. First, the addition of constraining wells, encountering old volcanic rocks lying above but near pre-Cenozoic basement, prevents modeled basement from being too shallow. Second, an extensive literature and well data search has led to an increased understanding of the change of rock density with depth in the vicinity of Rainier Mesa. The third, and most important change, relates to the application of several depth-density relationships in the study area instead of a single generalized relationship, thereby improving the overall model fit. In general, the pre-Cenozoic basement surface deepens in the western part of the study area, delineating collapses within the Silent Canyon and Timber Mountain caldera complexes, and shallows in the east in the Eleana Range and Yucca Flat regions, where basement crops out. In the Rainier Mesa study area, basement is generally shallow (< 1 km). The new model identifies previously unrecognized structures within the pre-Cenozoic basement that may influence ground-water flow, such as a shallow basement ridge related to an inferred fault extending northward from Rainier Mesa into Kawich Valley.

  17. Inversion of Gravity Data to Define the Pre-Cenozoic Surface and Regional Structures Possibly Influencing Groundwater Flow in the Rainier Mesa Region, Nye County, Nevada.

    Energy Technology Data Exchange (ETDEWEB)

    Thomas G. Hildenbrand; Geoffrey A. Phelps; Edward A. Mankinen

    2006-09-21

    A three-dimensional inversion of gravity data from the Rainier Mesa area and surrounding regions reveals a topographically complex pre-Cenozoic basement surface. This model of the depth to pre-Cenozoic basement rocks is intended for use in a 3D hydrogeologic model being constructed for the Rainier Mesa area. Prior to this study, our knowledge of the depth to pre-Cenozoic basement rocks was based on a regional model, applicable to general studies of the greater Nevada Test Site area but inappropriate for higher resolution modeling of ground-water flow across the Rainier Mesa area. The new model incorporates several changes that lead to significant improvements over the previous regional view. First, the addition of constraining wells, encountering old volcanic rocks lying above but near pre-Cenozoic basement, prevents modeled basement from being too shallow. Second, an extensive literature and well data search has led to an increased understanding of the change of rock density with depth in the vicinity of Rainier Mesa. The third, and most important change, relates to the application of several depth-density relationships in the study area instead of a single generalized relationship, thereby improving the overall model fit. In general, the pre-Cenozoic basement surface deepens in the western part of the study area, delineating collapses within the Silent Canyon and Timber Mountain caldera complexes, and shallows in the east in the Eleana Range and Yucca Flat regions, where basement crops out. In the Rainier Mesa study area, basement is generally shallow (< 1 km). The new model identifies previously unrecognized structures within the pre-Cenozoic basement that may influence ground-water flow, such as a shallow basement ridge related to an inferred fault extending northward from Rainier Mesa into Kawich Valley.

  18. A hedgehog-responsive region in the Drosophila wing disc is defined by debra-mediated ubiquitination and lysosomal degradation of Ci.

    Science.gov (United States)

    Dai, Ping; Akimaru, Hiroshi; Ishii, Shunsuke

    2003-06-01

    Transcription factor Ci mediates Hedgehog (Hh) signaling to determine the anterior/posterior (A/P) compartment of Drosophila wing disc. While Hh-inducible genes are expressed in A compartment cells abutting the A/P border, it is unclear how the boundaries of this region are established. Here, we have identified a Ci binding protein, Debra, that is expressed at relatively high levels in the band abutting the border of the Hh-responsive A compartment region. Debra mediates the polyubiquitination of full-length Ci, which then leads to its lysosomal degradation. Debra is localized in the multivesicular body, suggesting that the polyubiquitination of Ci directs its sorting into lysosome. Thus, Debra defines the border of the Hh-responsive region in the A compartment by inducing the lysosomal degradation of Ci.

  19. 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.

  20. 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.)

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

    Science.gov (United States)

    Brooks, Samantha J; Barker, Gareth J; O'Daly, Owen G; Brammer, Michael; Williams, Steven C R; Benedict, Christian; Schiöth, Helgi B; Treasure, Janet; Campbell, Iain C

    2011-11-17

    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. 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). 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. 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.

  2. 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

  3. 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:

  4. Response of face-selective brain regions to trustworthiness and gender of faces.

    Science.gov (United States)

    Mattavelli, Giulia; Andrews, Timothy J; Asghar, Aziz U R; Towler, John R; Young, Andrew W

    2012-07-01

    Neuropsychological and neuroimaging studies have demonstrated a role for the amygdala in processing the perceived trustworthiness of faces, but it remains uncertain whether its responses are linear (with the greatest response to the least trustworthy-looking faces), or quadratic (with increased fMRI signal for the dimension extremes). It is also unclear whether the trustworthiness of the stimuli is crucial or if the same response pattern can be found for faces varying along other dimensions. In addition, the responses to perceived trustworthiness of face-selective regions other than the amygdala are seldom reported. The present study addressed these issues using a novel set of stimuli created through computer image-manipulation both to maximise the presence of naturally occurring cues that underpin trustworthiness judgments and to allow systematic manipulation of these cues. With a block-design fMRI paradigm, we investigated neural responses to computer-manipulated trustworthiness in the amygdala and core face-selective regions in the occipital and temporal lobes. We asked whether the activation pattern is specific for differences in trustworthiness or whether it would also track variation along an orthogonal male-female gender dimension. The main findings were quadratic responses to changes in both trustworthiness and gender in all regions. These results are consistent with the idea that face-responsive brain regions are sensitive to face distinctiveness as well as the social meaning of the face features. Copyright © 2012 Elsevier Ltd. All rights reserved.

  5. Region-Specific Protein Abundance Changes in the Brain of MPTP-induced Parkinson’s Disease Mouse Model

    Energy Technology Data Exchange (ETDEWEB)

    Zhang, Xu; Zhou, Jianying; Chin, Mark H; Schepmoes, Athena A; Petyuk, Vladislav A; Weitz, Karl K; Petritis, Brianne O; Monroe, Matthew E; Camp, David G; Wood, Stephen A; Melega, William P; Bigelow, Diana J; Smith, Desmond J; Qian, Weijun; Smith, Richard D

    2010-02-15

    Parkinson’s disease (PD) is characterized by dopaminergic neurodegeneration in the nigrostriatal region of the brain; however, the neurodegeneration extends well beyond dopaminergic neurons. To gain a better understanding of the molecular changes relevant to PD, we applied two-dimensional LC-MS/MS to comparatively analyze the proteome changes in four brain regions (striatum, cerebellum, cortex, and the rest of brain) using a MPTP-induced PD mouse model with the objective to identify nigrostriatal-specific and other region-specific protein abundance changes. The combined analyses resulted in the identification of 4,895 non-redundant proteins with at least two unique peptides per protein. The relative abundance changes in each analyzed brain region were estimated based on the spectral count information. A total of 518 proteins were observed with significant MPTP-induced changes across different brain regions. 270 of these proteins were observed with specific changes occurring either only in the striatum and/or in the rest of the brain region that contains substantia nigra, suggesting that these proteins are associated with the underlying nigrostriatal pathways. Many of the proteins that exhibit significant abundance changes were associated with dopamine signaling, mitochondrial dysfunction, the ubiquitin system, calcium signaling, the oxidative stress response, and apoptosis. A set of proteins with either consistent change across all brain regions or with changes specific to the cortex and cerebellum regions were also detected. One of the interesting proteins is ubiquitin specific protease (USP9X), a deubiquination enzyme involved in the protection of proteins from degradation and promotion of the TGF-β pathway, which exhibited altered abundances in all brain regions. Western blot validation showed similar spatial changes, suggesting that USP9X is potentially associated with neurodegeneration. Together, this study for the first time presents an overall picture of

  6. Fish-assemblage variation between geologically defined regions and across a longitudinal gradient in the Monkey River Basin, Belize

    Science.gov (United States)

    Esselman, P.C.; Freeman, Mary C.; Pringle, C.M.

    2006-01-01

    Linkages between geology and fish assemblages have been inferred in many regions throughout the world, but no studies have yet investigated whether fish assemblages differ across geologies in Mesoamerica. The goals of our study were to: 1) compare physicochemical conditions and fish-assemblage structure across 2 geologic types in headwaters of the Monkey River Basin, Belize, and 2) describe basin-scale patterns in fish community composition and structure for the benefit of conservation efforts. We censused headwater-pool fishes by direct observation, and assessed habitat size, structure, and water chemistry to compare habitat and fish richness, diversity, evenness, and density between streams in the variably metamorphosed sedimentary geologic type typical of 80% of Belize's Maya Mountains (the Santa Rosa Group), and an anomalous extrusive geologic formation in the same area (the Bladen Volcanic Member). We also collected species-presence data from 20 sites throughout the basin for analyses of compositional patterns from the headwaters to the top of the estuary. Thirty-nine fish species in 21 families were observed. Poeciliids were numerically dominant, making up 39% of individuals captured, followed by characins (25%), and cichlids (20%). Cichlidae was the most species-rich family (7 spp.), followed by Poeciliidae (6 spp.). Habitat size and water chemistry differed strongly between geologic types, but habitat diversity did not. Major fish-assemblage differences also were not obvious between geologies, despite a marked difference in the presence of the aquatic macrophyte, Marathrum oxycarpum (Podostemaceae), which covered 37% of the stream bottom in high-nutrient streams draining the Santa Rosa Group, and did not occur in the low-P streams draining the Bladen Volcanic Member. Correlation analyses suggested that distance from the sea and amount of cover within pools are important to fish-assemblage structure, but that differing abiotic factors may influence

  7. Anorexia nervosa is linked to reduced brain structure in reward and somatosensory regions: a meta-analysis of VBM studies.

    Science.gov (United States)

    Titova, Olga E; Hjorth, Olof C; Schiöth, Helgi B; Brooks, Samantha J

    2013-04-09

    Structural imaging studies demonstrate brain tissue abnormalities in eating disorders, yet a quantitative analysis has not been done. In global and regional meta-analyses of 9 voxel-based morphometry (VBM) studies, with a total of 228 eating disorder participants (currently ill with anorexia nervosa), and 240 age-matched healthy controls, we compare brain volumes using global and regional analyses. Anorexia nervosa (AN) patients have global reductions in gray (effect size = -0.66) and white matter (effect size = -0.74) and increased cerebrospinal fluid (effect size = 0.98) and have regional decreases in left hypothalamus, left inferior parietal lobe, right lentiform nucleus and right caudate, and no significant increases. No significant difference in hemispheric lateralization was found. Global and regional meta-analyses suggest that excessive restrained eating as found in those with anorexia nervosa coincides with structural brain changes analogous to clinical symptoms.

  8. 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

  9. 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).

  10. Frequency specificity of regional homogeneity in the resting-state human brain.

    Directory of Open Access Journals (Sweden)

    Xiaopeng Song

    Full Text Available Resting state-fMRI studies have found that the inter-areal correlations in cortical networks concentrate within ultra-low frequencies (0.01-0.04 Hz while long-distance connections within subcortical networks distribute over a wider frequency range (0.01-0.14 Hz. However, the frequency characteristics of regional homogeneity (ReHo in different areas are still unclear. To examine the ReHo properties in different frequency bands, a data-driven method, Empirical Mode Decomposition (EMD, was adopted to decompose the time series of each voxel into several components with distinct frequency bands. ReHo values in each of the components were then calculated. Our results showed that ReHo in cortical areas were higher and more frequency-dependent than those in the subcortical regions. BOLD oscillations of 0.02-0.04 Hz mainly contributed to the cortical ReHo, whereas the ReHo in limbic areas involved a wider frequency range and were dominated by higher-frequency BOLD oscillations (>0.08 Hz. The frequency characteristics of ReHo are distinct between different parts of the striatum, with the frequency band of 0.04-0.1 Hz contributing the most to ReHo in caudate nucleus, and oscillations lower than 0.02 Hz contributing more to ReHo in putamen. The distinct frequency-specific ReHo properties of different brain areas may arise from the assorted cytoarchitecture or synaptic types in these areas. Our work may advance the understanding of the neural-physiological basis of local BOLD activities and the functional specificity of different brain regions.

  11. Monoamines tissue content analysis reveals restricted and site-specific correlations in brain regions involved in cognition.

    Science.gov (United States)

    Fitoussi, A; Dellu-Hagedorn, F; De Deurwaerdère, P

    2013-01-01

    The dopamine (DA), noradrenalin (NA) and serotonin (5-HT) monoaminergic systems are deeply involved in cognitive processes via their influence on cortical and subcortical regions. The widespread distribution of these monoaminergic networks is one of the main difficulties in analyzing their functions and interactions. To address this complexity, we assessed whether inter-individual differences in monoamine tissue contents of various brain areas could provide information about their functional relationships. We used a sensitive biochemical approach to map endogenous monoamine tissue content in 20 rat brain areas involved in cognition, including 10 cortical areas and examined correlations within and between the monoaminergic systems. Whereas DA content and its respective metabolite largely varied across brain regions, the NA and 5-HT contents were relatively homogenous. As expected, the tissue content varied among individuals. Our analyses revealed a few specific relationships (10%) between the tissue content of each monoamine in paired brain regions and even between monoamines in paired brain regions. The tissue contents of NA, 5-HT and DA were inter-correlated with a high incidence when looking at a specific brain region. Most correlations found between cortical areas were positive while some cortico-subcortical relationships regarding the DA, NA and 5-HT tissue contents were negative, in particular for DA content. In conclusion, this work provides a useful database of the monoamine tissue content in numerous brain regions. It suggests that the regulation of these neuromodulatory systems is achieved mainly at the terminals, and that each of these systems contributes to the regulation of the other two.

  12. Regional brain monoamine concentrations and their alterations in bovine hypomagnesaemic tetany experimentally induced by a magnesium-deficient diet.

    Science.gov (United States)

    McCoy, M A; Young, P B; Hudson, A J; Davison, G; Kennedy, D G

    2000-12-01

    Monoamines are important brain neurotransmitters. An investigation was carried out to determine if hypomagnesaemic tetany was associated with alterations in regional brain monoamine concentrations in bovines. The results, established in cows with normal magnesium status, demonstrated that regional differences existed in the distribution and concentration of brain monoamines in the adult bovine, which were similar to those in other species. In magnesium-deficient cows, severe hypomagnesaemia and lowered cerebrospinal fluid (CSF) magnesium concentrations were associated with significant alterations in monoamine concentrations in some brain regions. Alterations in 3,4-dihydroxyphenylalanine (DOPA) and dihydroxyphenylacetic acid (DOPAC) concentrations in the corpus striatum, and dopamine (DA) in the cerebral cortex and cerebellum were recorded. These regions play an important role in both voluntary and involuntary motor function, and therefore these alterations may play a role in the aetiology of hypomagnesaemic tetany. However, there was no significant change in DA concentrations in the corpus striatum (the main dopaminergic region in the brain) associated with hypomagnesaemia. In addition, a significantly lower norepinephrine (NE) concentration in the corpus striatum of hypomagnesaemic animals was also recorded. Norephinephrine is generally excitatory and therefore lowered NE concentrations would be expected to result in depression rather than stimulation of motor function. Copyright 2000 Harcourt Publishers Ltd.

  13. Use of Relative vs Fixed Offset Distance to Define Region of Interest at the Distal Radius and Tibia in High-Resolution Peripheral Quantitative Computed Tomography.

    Science.gov (United States)

    Shanbhogue, Vikram V; Hansen, Stinus; Halekoh, Ulrich; Brixen, Kim

    2015-01-01

    Although the region of interest in high-resolution peripheral quantitative computed tomography, defined based on the manufacturer's protocol for in vivo scanning, provides consistency and is practically convenient, it does not take into account possible variation in morphology in the regions adjacent to the measurement site. This study aimed at compare the morphologic variation in measurements using the standard fixed offset distance to define the distal starting slice against those obtained by using a relative measurement position scaled to the individual bone length at the distal radius and tibia in normal healthy adult subjects. A total of 40 healthy adult subjects (median height, 175.3 cm; range: 150.0-196.0 cm) were included in the study. High-resolution peripheral quantitative computed tomography at the distal radius and tibia was performed in all subjects, the region of interest defined by, first, the standard measurement protocol, where the most distal CT slice was 9.5 mm and 22.5 mm from the end plate of the radius and tibia, respectively, and second, the relative measurement method, where the most distal CT slice was at 4% and 7% of the radial and tibial lengths, respectively. Volumetric densities and microarchitectural parameters were compared between the 2 methods. Measurements of the total and cortical volumetric density and cortical thickness at the radius and tibia and cortical porosity, trabecular volumetric density, and trabecular number at the tibia were significantly different between the 2 methods (all p radius (up to 34%) and the tibia (up to 36%). A lack of consideration to height (and in turn the bone lengths) in the standard patient protocol could lead to the introduction of systematic errors in radial and tibial measurements. Although this may not be of particular significance in longitudinal studies in the same individual, it potentially assumes critical importance in cross-sectional studies.

  14. An acute dose of gamma-hydroxybutyric acid alters gene expression in multiple mouse brain regions.

    Science.gov (United States)

    Schnackenberg, B J; Saini, U T; Robinson, B L; Ali, S F; Patterson, T A

    2010-10-13

    Gamma-hydroxybutyric acid (GHB) is normally found in the brain in low concentrations and may function as a neurotransmitter, although the mechanism of action has not been completely elucidated. GHB has been used as a general anesthetic and is currently used to treat narcolepsy and alcoholism. Recreational use of GHB is primarily as a "club drug" and a "date rape drug," due to its amnesic effects. For this study, the hypothesis was that behavioral and neurochemical alterations may parallel gene expression changes in the brain after GHB administration. Adult male C57/B6N mice (n=5/group) were administered a single dose of 500 mg/kg GHB (i.p.) and were sacrificed 1, 2 and 4 h after treatment. Control mice were administered saline. Brains were removed and regionally dissected on ice. Total RNA from the hippocampus, cortex and striatum was extracted, amplified and labeled. Gene expression was evaluated using Agilent whole mouse genome 4x44K oligonucleotide microarrays. Microarray data were analyzed by ArrayTrack and differentially expressed genes (DEGs) were identified using P or = 1.7 as the criteria for significance. Principal component analysis (PCA) and Hierarchical Cluster Analysis (HCA) showed that samples from each time point clustered into distinct treatment groups with respect to sacrifice time. Ingenuity pathways analysis (IPA) was used to identify involved pathways. The results show that GHB induces gene expression alterations in hundreds of genes in the hippocampus, cortex and striatum, and the number of affected genes increases throughout a 4-h time course. Many of these DEGs are involved in neurological disease, apoptosis, and oxidative stress.

  15. A Comparative Antibody Analysis of Pannexin1 Expression in Four Rat Brain Regions Reveals Varying Subcellular Localizations

    OpenAIRE

    Cone, Angela C.; Ambrosi, Cinzia; Scemes, Eliana; Maryann E. Martone; Sosinsky, Gina E.

    2013-01-01

    Pannexin1 (Panx1) channels release cytosolic ATP in response to signaling pathways. Panx1 is highly expressed in the central nervous system. We used four antibodies with different Panx1 anti-peptide epitopes to analyze four regions of rat brain. These antibodies labeled the same bands in Western blots and had highly similar patterns of immunofluorescence in tissue culture cells expressing Panx1, but Western blots of brain lysates from Panx1 knockout and control mice showed different banding p...

  16. Quantitative map of multiple auditory cortical regions with a stereotaxic fine-scale atlas of the mouse brain

    OpenAIRE

    Hiroaki Tsukano; Masao Horie; Ryuichi Hishida; Kuniyuki Takahashi; Hirohide Takebayashi; Katsuei Shibuki

    2016-01-01

    Optical imaging studies have recently revealed the presence of multiple auditory cortical regions in the mouse brain. We have previously demonstrated, using flavoprotein fluorescence imaging, at least six regions in the mouse auditory cortex, including the anterior auditory field (AAF), primary auditory cortex (AI), the secondary auditory field (AII), dorsoanterior field (DA), dorsomedial field (DM), and dorsoposterior field (DP). While multiple regions in the visual cortex and somatosensory ...

  17. Obesity and insulin resistance are associated with reduced activity in core memory regions of the brain.

    Science.gov (United States)

    Cheke, Lucy G; Bonnici, Heidi M; Clayton, Nicola S; Simons, Jon S

    2017-02-01

    Increasing research in animals and humans suggests that obesity may be associated with learning and memory deficits, and in particular with reductions in episodic memory. Rodent models have implicated the hippocampus in obesity-related memory impairments, but the neural mechanisms underlying episodic memory deficits in obese humans remain undetermined. In the present study, lean and obese human participants were scanned using fMRI while completing a What-Where-When episodic memory test (the "Treasure-Hunt Task") that assessed the ability to remember integrated item, spatial, and temporal details of previously encoded complex events. In lean participants, the Treasure-Hunt task elicited significant activity in regions of the brain known to be important for recollecting episodic memories, such as the hippocampus, angular gyrus, and dorsolateral prefrontal cortex. Both obesity and insulin resistance were associated with significantly reduced functional activity throughout the core recollection network. These findings indicate that obesity is associated with reduced functional activity in core brain areas supporting episodic memory and that insulin resistance may be a key player in this association. Copyright © 2017 The Authors. Published by Elsevier Ltd.. All rights reserved.

  18. Synaptic proteome changes in mouse brain regions upon auditory discrimination learning.

    Science.gov (United States)

    Kähne, Thilo; Kolodziej, Angela; Smalla, Karl-Heinz; Eisenschmidt, Elke; Haus, Utz-Uwe; Weismantel, Robert; Kropf, Siegfried; Wetzel, Wolfram; Ohl, Frank W; Tischmeyer, Wolfgang; Naumann, Michael; Gundelfinger, Eckart D

    2012-08-01

    Changes in synaptic efficacy underlying learning and memory processes are assumed to be associated with alterations of the protein composition of synapses. Here, we performed a quantitative proteomic screen to monitor changes in the synaptic proteome of four brain areas (auditory cortex, frontal cortex, hippocampus striatum) during auditory learning. Mice were trained in a shuttle box GO/NO-GO paradigm to discriminate between rising and falling frequency modulated tones to avoid mild electric foot shock. Control-treated mice received corresponding numbers of either the tones or the foot shocks. Six hours and 24 h later, the composition of a fraction enriched in synaptic cytomatrix-associated proteins was compared to that obtained from naïve mice by quantitative mass spectrometry. In the synaptic protein fraction obtained from trained mice, the average percentage (±SEM) of downregulated proteins (59.9 ± 0.5%) exceeded that of upregulated proteins (23.5 ± 0.8%) in the brain regions studied. This effect was significantly smaller in foot shock (42.7 ± 0.6% down, 40.7 ± 1.0% up) and tone controls (43.9 ± 1.0% down, 39.7 ± 0.9% up). These data suggest that learning processes initially induce removal and/or degradation of proteins from presynaptic and postsynaptic cytoskeletal matrices before these structures can acquire a new, postlearning organisation. In silico analysis points to a general role of insulin-like signalling in this process.

  19. The role of right frontal brain regions in integration of spatial relation.

    Science.gov (United States)

    Han, Jiahui; Cao, Bihua; Cao, Yunfei; Gao, Heming; Li, Fuhong

    2016-06-01

    Previous studies have explored the neural mechanisms of spatial reasoning on a two-dimensional (2D) plane; however, it remains unclear how spatial reasoning is conducted in a three-dimensional (3D) condition. In the present study, we presented 3D geometric objects to 16 adult participants, and asked them to process the spatial relationship between different corners of the geometric objects. In premise-1, the first two corners of a geometric shape (e.g., A vs. B) were displayed. In premise-2, the second and third corners (e.g., B vs. C) were displayed. After integrating the two premises, participants were required to infer the spatial relationship between the first and the third corners (e.g., A and C). Finally, the participants were presented with a conclusion object, and they were required to judge whether the conclusion was true or false based on their inference. The event-related potential evoked by premise-2 revealed that (1) compared with 2D spatial reasoning, 3D reasoning elicited a smaller P3b component, and (2) in the right frontal areas, increased negativities were found in the 3D condition during the N400 and late negative components (LNC). These findings imply that higher brain activity in the right frontal brain regions were related with the integration and maintenance of spatial information in working memory for reasoning.

  20. Perfluorooctane sulfonate (PFOS) exposure could modify the dopaminergic system in several limbic brain regions.

    Science.gov (United States)

    Salgado, R; López-Doval, S; Pereiro, N; Lafuente, A

    2016-01-05

    Perfluorooctane sulfonate (PFOS) is the most representative of a rising class of persistent organic pollutants perfluorochemicals. In the present study, its neurotoxicity was examined using adult male rats orally treated with 0.5; 1.0; 3.0 and 6.0 mg of PFOS/kg/day for 28 days. At the end of the treatment, the dopamine concentration and its metabolism expressed like the ratio 3,4-dihydroxyphenylacetic acid (DOPAC)/dopamine and homovanillic acid (HVA)/dopamine were measured in the amygdala, prefrontal cortex and hippocampus. Gene and protein expression of the dopamine receptors D1 and D2 were also determined in these limbic areas. The obtained results suggest that: (1) PFOS can alter the dopamine system by modifying its neuronal activity and/or its D1 and D2 receptors in the studied brain regions; (2) the dopamine concentration and metabolism seem to be more sensitive against PFOS toxicity in the hippocampus than in the other analyzed brain areas; (3) the inhibited gene and protein expression of the D1 receptors induced by PFOS in the amygdala could be related to several changes in the HPA axis activity, and lastly; (4) the observed alterations on the dopamine system induced by PFOS could be a possible neurotoxicity mechanism of PFOS, leading to many neurological diseases.

  1. Regional brain activation as a biological marker of affective responsivity to acute exercise: influence of fitness.

    Science.gov (United States)

    Petruzzello, S J; Hall, E E; Ekkekakis, P

    2001-01-01

    Previous research has shown that regional brain activation, assessed via frontal electroencephalographic (EEG) asymmetry, predicts affective responsivity to aerobic exercise. To replicate and extend this work, in the present study we examined whether resting brain activation was associated with affective responses to an acute bout of aerobic exercise and the extent to which aerobic fitness mediated this relationship. Participants (high-fit, n = 22; low/moderate-fit, n = 45) ran on a treadmill for 30 min at 75% VO2max. EEG and affect were assessed pre- and 0-, 10-, 20-, and 30-min postexercise. Resting EEG asymmetry predicted positive affect (as measured by the energetic arousal subscale of the Activation Deactivation Adjective Check List) postexercise. Furthermore, resting frontal EEG asymmetry predicted affect only in the high-fit group, suggesting the effect might be mediated by some factor related to fitness. It was also shown that subjects with relatively greater left frontal activation had significantly more energy (i.e., activated pleasant affect) following exercise than subjects with relatively greater right frontal activation. In conclusion, aerobic fitness influenced the relationship between resting frontal asymmetry and exercise-related affective responsivity.

  2. Direct profiling of myelinated and demyelinated regions in mouse brain by imaging mass spectrometry

    Science.gov (United States)

    Ceuppens, Ruben; Dumont, Debora; van Brussel, Leen; van de Plas, Babs; Daniels, Ruth; Noben, Jean-Paul; Verhaert, Peter; van der Gucht, Estel; Robben, Johan; Clerens, Stefan; Arckens, Lutgarde

    2007-02-01

    One of the newly developed imaging mass spectrometry (IMS) technologies utilizes matrix-assisted laser desorption/ionization (MALDI) mass spectrometry to map proteins in thin tissue sections. In this study, we evaluated the power of MALDI IMS as we developed it in our (Bruker) MALDI TOF (Reflex IV) and TOF-TOF (Ultraflex II) systems to study myelin patterns in the mouse central nervous system under normal and pathological conditions. MALDI IMS was applied to assess myelin basic protein (MBP) isoform-specific profiles in different regions throughout the mouse brain. The distribution of ions of m/z 14,144 and 18,447 displayed a striking resemblance with white matter histology and were identified as MBP isoform 8 and 5, respectively. In addition, we demonstrated a significant reduction of the MBP-8 peak intensity upon MALDI IMS analysis of focal ethidium bromide-induced demyelinated brain areas. Our MS images were validated by immunohistochemistry using MBP antibodies. This study underscores the potential of MALDI IMS to study the contribution of MBP to demyelinating diseases.

  3. 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.)

  4. Expression of Bcl-2 in adult human brain regions with special reference to neurodegenerative disorders.

    Science.gov (United States)

    Vyas, S; Javoy-Agid, F; Herrero, M T; Strada, O; Boissiere, F; Hibner, U; Agid, Y

    1997-07-01

    The expression of the protooncogene bcl-2, an inhibitor of apoptosis in various cells, was examined in the adult human brain. Several experimental criteria were used to verify its presence; mRNA was analyzed by northern blot with parallel experiments in mouse tissues, by RNase protection, and by in situ hybridization histochemistry. Bcl-2 protein was detected by western blot analysis and immunohistochemistry. Two bcl-2 mRNA species were identified in the human brain. The pattern of distribution of bcl-2 mRNA at the cellular level showed labeling in neurons but not glia. The in situ hybridization signal was stronger in the pyramidal neurons of the cerebral cortex and in the cholinergic neurons of the nucleus basalis of Meynert than in the Purkinje neurons of the cerebellum. Both melanized and nonmelanized neurons were labeled in the substantia nigra. In the striatum, bcl-2 mRNA was detected in some but not all neurons. In the regions examined for Bcl-2 protein, the expression pattern correlated with the mRNA results. In patients with Alzheimer's and Parkinson's diseases, quantification of bcl-2 mRNA in the nucleus basalis of Meynert and substantia nigra, respectively, showed that the expression was unaltered compared with controls, raising the possibility that the expression of other components of apoptosis is modulated.

  5. Brain regions associated with Anhedonia in healthy adults: a PET correlation study

    Energy Technology Data Exchange (ETDEWEB)

    Jung, Young Chul; Chun, Ji Won; Kim, Jae Jin; Park, Hae Jeong; Lee, Jong Doo [Yonsei University College of Medicine, Gwangju (Korea, Republic of); Seok, Jeong Ho [Hallym University Sacred Heart Hospital, Anyang (Korea, Republic of)

    2005-10-15

    Anhedonia has been proposed to be the result of a basic neurophysiologic dysfunction and a vulnerability marker that precede and contribute to the liability of developing schizophrenia. We hypothesized that anhedonia, as a construct reflecting the decreased capacity to experience pleasure, should be associated with decreased positive hedonic affect trait. This study examined the relationship between anhedonia and positive hedonic affect trait and searched for the brain regions which correlate with anhedonia in normal subjects. Using {sup 18}F-FDG PET scan, we investigated the brain activity of twenty one subjects during resting state. Questionnaires were administrated after the scan in order to assess the self-rated individual differences in physical/social anhedonia and positive/negative affect traits. Negative correlation between physical anhedonia score and positive affect trait score was significant (Pearson coefficient=-0.440, {rho} <0.05). The subjects' physical and social anhedonia scores showed positive correlation with metabolic rates in the cerebellum and negative correlation with metabolic rates in the inferior temporal gyrus and middle frontal gyrus. In addition, the positive affect trait score positively correlated with various areas, most prominent with the inferior temporal gyrus. These results suggest that neural substrates, such as the inferior temporal gyrus and prefrontal-cerebellar circuit, which dysfunction has been proposed to be involved with the cognitive deficits of schizophrenia, may also play a significant role in the liability of affective deficits like anhedonia.

  6. Acute treatment with fluvoxamine elevates rat brain serotonin synthesis in some terminal regions: An autoradiographic study

    Science.gov (United States)

    Muck-Seler, Dorotea; Pivac, Nela; Diksic, Mirko

    2013-01-01

    Introduction A considerable body of evidence indicates the involvement of the neurotransmitter serotonin (5-HT) in the pathogenesis and treatment of depression. Methods The acute effect of fluvoxamine, on 5-HT synthesis rates was investigated in rat brain regions, using α-14C-methyl-L-tryptophan as a tracer. Fluvoxamine (25 mg/kg) and saline (control) were injected intraperitoneally, one hour before the injection of the tracer (30 μCi). Results There was no significant effect of fluvoxamine on plasma free tryptophan. After Benjamini–Hochberg False Discovery Rate correction, a significant decrease in the 5-HT synthesis rate in the fluvoxamine treated rats, was found in the raphe magnus (−32%), but not in the median (−14%) and dorsal (−3%) raphe nuclei. In the regions with serotonergic axon terminals, significant increases in synthesis rates were observed in the dorsal (+41%) and ventral (+43%) hippocampus, visual (+38%), auditory (+65%) and parietal (+37%) cortex, and the substantia nigra pars compacta (+56%). There were no significant changes in the 5-HT synthesis rates in the median (+11%) and lateral (+24%) part of the caudate-putamen, nucleus accumbens (+5%), VTA (+16%) or frontal cortex (+ 6%). Conclusions The data show that the acute administration of fluvoxamine affects 5-HT synthesis rates in a regionally specific pattern, with a general elevation of the synthesis in the terminal regions and a reduction in some cell body structures. The reasons for the regional specific effect of fluvoxamine on 5-HT synthesis are unclear, but may be mediated by the presynaptic serotonergic autoreceptors. PMID:22560971

  7. 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.

    2015-01-01

    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. PMID:26350727

  8. Effects of alcohol consumption on cognition and regional brain volumes among older adults.

    Science.gov (United States)

    Downer, Brian; Jiang, Yang; Zanjani, Faika; Fardo, David

    2015-06-01

    This study utilized data from the Framingham Heart Study Offspring Cohort to examine the relationship between midlife and late-life alcohol consumption, cognitive functioning, and regional brain volumes among older adults without dementia or a history of abusing alcohol. The results from multiple linear regression models indicate that late life, but not midlife, alcohol consumption status is associated with episodic memory and hippocampal volume. Compared to late life abstainers, moderate consumers had larger hippocampal volume, and light consumers had higher episodic memory. The differences in episodic memory according to late life alcohol consumption status were no longer significant when hippocampal volume was included in the regression model. The findings from this study provide new evidence that hippocampal volume may contribute to the observed differences in episodic memory among older adults and late life alcohol consumption status.

  9. Multivariate evaluation of brain function by measuring regional cerebral blood flow and event-related potentials

    Energy Technology Data Exchange (ETDEWEB)

    Koga, Yoshihiko; Mochida, Masahiko; Shutara, Yoshikazu; Nakagawa, Kazumi [Kyorin Univ., Mitaka, Tokyo (Japan). School of Medicine; Nagata, Ken

    1998-07-01

    To measure the effect of events on human cognitive function, effects of odors by measurement regional cerebral blood flow (rCBF) and P300 were evaluated during the auditory odd-ball exercise. PET showed the increase in rCBF on the right hemisphere of the brain by coffee aroma. rCBF was measured by PET in 9 of right-handed healthy adults men, and P300 was by event-related potential (ERP) in each sex of 20 right-handed healthy adults. ERP showed the difference of the P300 amplitude between men and women, and showed the tendency, by odors except the lavender oil, that women had higher in the P300 amplitude than men. These results suggest the presence of effects on the cognitive function through emotional actions. Next, the relationship between rCBF and ERP were evaluated. The subjects were 9 of the right-handed healthy adults (average: 25.6{+-}3.4 years old). rCBF by PET and P300 amplitude by ERP were simultaneously recorded during the auditory odd-ball exercise using the tone-burst method (2 kHz of the low frequency aimed stimuli and 1 kHz of the high frequency non-aimed stimuli). The rCBF value was the highest at the transverse gyrus of Heschl and the lowest at the piriform cortex among 24 regions of interest (ROI) from both sides. The difference of P300 peak latent time among ROI was almost the same. The brain waves from Cz and Pz were similar and the average amplitude was highest at Pz. We found the high correlation in the right piriform cortex (Fz), and right (Fz, Cz) and left (Cz, Pz) transverse gyrus of Heschl between the P300 amplitude and rCBF. (K.H.)

  10. Measuring structural-functional correspondence: spatial variability of specialised brain regions after macro-anatomical alignment.

    Science.gov (United States)

    Frost, Martin A; Goebel, Rainer

    2012-01-16

    The central question of the relationship between structure and function in the human brain is still not well understood. In order to investigate this fundamental relationship we create functional probabilistic maps from a large set of mapping experiments and compare the location of functionally localised regions across subjects using different whole-brain alignment schemes. To avoid the major problems associated with meta-analysis approaches, all subjects are scanned using the same paradigms, the same scanner and the same analysis pipeline. We show that an advanced, curvature driven cortex based alignment (CBA) scheme largely removes macro-anatomical variability across subjects. Remaining variability in the observed spatial location of functional regions, thus, reflects the "true" functional variability, i.e. the quantified variability is a good estimator of the underlying structural-functional correspondence. After localising 13 widely studied functional areas, we found a large variability in the degree to which functional areas respect macro-anatomical boundaries across the cortex. Some areas, such as the frontal eye fields (FEF) are strongly bound to a macro-anatomical location. Fusiform face area (FFA) on the other hand, varies in its location along the length of the fusiform gyrus even though the gyri themselves are well aligned across subjects. Language areas were found to vary greatly across subjects whilst a high degree of overlap was observed in sensory and motor areas. The observed differences in functional variability for different specialised areas suggest that a more complete estimation of the structure-function relationship across the whole cortex requires further empirical studies with an expanded test battery.

  11. Large field-of-view and depth-specific cortical microvascular imaging underlies regional differences in ischemic brain

    Science.gov (United States)

    Qin, Jia; Shi, Lei; Dziennis, Suzan; Wang, Ruikang K.

    2014-02-01

    Ability to non-invasively monitor and quantify of blood flow, blood vessel morphology, oxygenation and tissue morphology is important for improved diagnosis, treatment and management of various neurovascular disorders, e.g., stroke. Currently, no imaging technique is available that can satisfactorily extract these parameters from in vivo microcirculatory tissue beds, with large field of view and sufficient resolution at defined depth without any harm to the tissue. In order for more effective therapeutics, we need to determine the area of brain that is damaged but not yet dead after focal ischemia. Here we develop an integrated multi-functional imaging system, in which SDW-LSCI (synchronized dual wavelength laser speckle imaging) is used as a guiding tool for OMAG (optical microangiography) to investigate the fine detail of tissue hemodynamics, such as vessel flow, profile, and flow direction. We determine the utility of the integrated system for serial monitoring afore mentioned parameters in experimental stroke, middle cerebral artery occlusion (MCAO) in mice. For 90 min MCAO, onsite and 24 hours following reperfusion, we use SDW-LSCI to determine distinct flow and oxygenation variations for differentiation of the infarction, peri-infarct, reduced flow and contralateral regions. The blood volumes are quantifiable and distinct in afore mentioned regions. We also demonstrate the behaviors of flow and flow direction in the arterials connected to MCA play important role in the time course of MCAO. These achievements may improve our understanding of vascular involvement under pathologic and physiological conditions, and ultimately facilitate clinical diagnosis, monitoring and therapeutic interventions of neurovascular diseases, such as ischemic stroke.

  12. Identification of the boundary between normal brain tissue and ischemia region using two-photon excitation fluorescence microscopy

    Science.gov (United States)

    Du, Huiping; Wang, Shu; Wang, Xingfu; Zhu, Xiaoqin; Zhuo, Shuangmu; Chen, Jianxin

    2016-10-01

    Ischemic stroke is one of the common neurological diseases, and it is becoming the leading causes of death and permanent disability around the world. Early and accurate identification of the potentially salvageable boundary region of ischemia brain tissues may enable selection of the most appropriate candidates for early stroke therapies. In this work, TPEF microscopy was used to image the microstructures of normal brain tissues, ischemia regions and the boundary region between normal and ischemia brain tissues. The ischemia brain tissues from Sprague-Dawley (SD) rats were subjected to 6 hours of middle cerebral artery occlusion (MCAO). Our study demonstrates that TPEF microscopy has the ability to not only reveal the morphological changes of the neurons but also identify the boundary between normal brain tissue and ischemia region, which correspond well to the hematoxylin and eosin (H and E) stained images. With the development of miniaturized TPEF microscope imaging devices, TPEF microscopy can be developed into an effectively diagnostic and monitoring tool for cerebral ischemia.

  13. Measuring the effects of aging and sex on regional brain stiffness with MR elastography in healthy older adults.

    Science.gov (United States)

    Arani, Arvin; Murphy, Matthew C; Glaser, Kevin J; Manduca, Armando; Lake, David S; Kruse, Scott A; Jack, Clifford R; Ehman, Richard L; Huston, John

    2015-05-01

    Changes in tissue composition and cellular architecture have been associated with neurological disease, and these in turn can affect biomechanical properties. Natural biological factors such as aging and an individual's sex also affect underlying tissue biomechanics in different brain regions. Understanding the normal changes is necessary before determining the efficacy of stiffness imaging for neurological disease diagnosis and therapy monitoring. The objective of this study was to evaluate global and regional changes in brain stiffness as a function of age and sex, using improved MRE acquisition and processing that have been shown to provide median stiffness values that are typically reproducible to within 1% in global measurements and within 2% for regional measurements. Furthermore, this is the first study to report the effects of age and sex over the entire cerebrum volume and over the full frontal, occipital, parietal, temporal, deep gray matter/white matter (insula, deep gray nuclei and white matter tracts), and cerebellum volumes. In 45 volunteers, we observed a significant linear correlation between age and brain stiffness in the cerebrum (Pcerebrum stiffness with a theoretical median age value (76 years old) of 2.56 ± 0.08 kPa. Sexual dimorphism was observed in the temporal (P=.03) and occipital (P=.001) lobes of the brain, but no significant difference was observed in any of the other brain regions (P>.20 for all other regions). The model predicted female occipital and temporal lobes to be 0.23 kPa and 0.09 kPa stiffer than males of the same age, respectively. This study confirms that as the brain ages, there is softening; however, the changes are dependent on region. In addition, stiffness effects due to sex exist in the occipital and temporal lobes. Copyright © 2015 The Authors. Published by Elsevier Inc. All rights reserved.

  14. The size of non-hippocampal brain regions varies by season and sex in Richardson's ground squirrel.

    Science.gov (United States)

    Keeley, R J; Burger, D K; Saucier, D M; Iwaniuk, A N

    2015-03-19

    Sex- and season-specific modulation of hippocampal size and function is observed across multiple species, including rodents. Other non-hippocampal-dependent behaviors exhibit season and sex differences, and whether the associated brain regions exhibit similar variation with sex and season remains to be fully characterized. As such, we examined the brains of wild-caught Richardson's ground squirrels (RGS; Urocitellus richardsonii) for seasonal (breeding, non-breeding) and sex differences in the volumes of specific brain areas, including: total brain volume, corpus callosum (CC), anterior commissure (AC), medial prefrontal cortex (mPFC), total neocortex (NC), entorhinal cortex (EC), and superior colliculus (SC). Analyses of variance and covariance revealed significant interactions between season and sex for almost all areas studied, primarily resulting from females captured during the breeding season exhibiting larger volumes than females captured during the non-breeding season. This was observed for volumes of the AC, mPFC, NC, EC, and SC. Where simple main effects of season were observed for males (the NC and the SC), the volume advantage favoured males captured during the NBr season. Only two simple main effects of sex were observed: males captured in the non-breeding season had significantly larger total brain volume than females captured in the non-breeding season, and females captured during the breeding season had larger volumes of the mPFC and EC than males captured in the breeding season. These results indicate that females have more pronounced seasonal differences in brain and brain region sizes. The extent to which seasonal differences in brain region volumes vary with behaviour is unclear, but our data do suggest that seasonal plasticity is not limited to the hippocampus and that RGS is a useful mammalian species for understanding seasonal plasticity in an ecologically relevant context.

  15. Brain regions involved in human movement perception: a quantitative voxel-based meta-analysis.

    Science.gov (United States)

    Grosbras, Marie-Hélène; Beaton, Susan; Eickhoff, Simon B

    2012-02-01

    Face, hands, and body movements are powerful signals essential for social interactions. In the last 2 decades, a large number of brain imaging studies have explored the neural correlates of the perception of these signals. Formal synthesis is crucially needed, however, to extract the key circuits involved in human motion perception across the variety of paradigms and stimuli that have been used. Here, we used the activation likelihood estimation (ALE) meta-analysis approach with random effect analysis. We performed meta-analyses on three classes of biological motion: movement of the whole body, hands, and face. Additional analyses of studies of static faces or body stimuli and sub-analyses grouping experiments as a function of their control stimuli or task employed allowed us to identify main effects of movements and forms perception, as well as effects of task demand. In addition to specific features, all conditions showed convergence in occipito-temporal and fronto-parietal regions, but with different peak location and extent. The conjunction of the three ALE maps revealed convergence in all categories in a region of the right posterior superior temporal sulcus as well as in a bilateral region at the junction between middle temporal and lateral occipital gyri. Activation in these regions was not a function of attentional demand and was significant also when controlling for non-specific motion perception. This quantitative synthesis points towards a special role for posterior superior temporal sulcus for integrating human movement percept, and supports a specific representation for body parts in middle temporal, fusiform, precentral, and parietal areas.

  16. Severity of nicotine dependence modulates cue-induced brain activity in regions involved in motor preparation and imagery.

    Science.gov (United States)

    Smolka, Michael N; Bühler, Mira; Klein, Sabine; Zimmermann, Ulrich; Mann, Karl; Heinz, Andreas; Braus, Dieter F

    2006-03-01

    In nicotine-dependent subjects, cues related to smoking elicit activity in brain regions linked to attention, memory, emotion and motivation. Cue-induced brain activation is associated with self-reported craving but further correlates are widely unknown. This study was conducted to investigate whether brain activity elicited by smoking cues increases with severity of nicotine dependence and intensity of cue-elicited craving. Ten healthy male smokers whose degree of nicotine dependence ranged from absent to severe were investigated. Visual smoking cues and neutral stimuli were presented in a block design during functional magnetic resonance imaging (fMRI). Using multiple linear regression analysis, the blood oxygen level dependent (BOLD) response to smoking cues was correlated with severity of nicotine dependence assessed with the Fagerström Test of Nicotine Dependence (FTND) and with cue-induced craving. Significant positive correlations between the BOLD activity and FTND scores were found in brain areas related to visuospatial attention (anterior cingulate cortex, parietal cortex, parahippocampal gyrus and cuneus) and in regions involved in motor preparation and imagery (primary and premotor cortex, supplementary motor area). Intensity of cue-induced craving was significantly associated with greater BOLD activation in mesocorticolimbic areas engaged in incentive motivation and in brain regions related to episodic memory. Our study suggests that severity of nicotine dependence and intensity of craving are independently associated with cue-induced brain activation in separate neuronal networks. The observed association between severity of dependence and brain activity in regions involved in allocation of attention, motor preparation and imagery might reflect preparation of automated drug taking behavior thereby facilitating cue-induced relapse.

  17. Neurobehavioral performances and brain regional metabolism in Dab1(scm) (scrambler) mutant mice.

    Science.gov (United States)

    Jacquelin, C; Lalonde, R; Jantzen-Ossola, C; Strazielle, C

    2013-09-01

    As disabled-1 (DAB1) protein acts downstream in the reelin signaling pathway modulating neuronal migration, glutamate neurotransmission, and cytoskeletal function, the disabled-1 gene mutation (scrambler or Dab1(scm) mutation) results in ataxic mice displaying dramatic neuroanatomical defects similar to those observed in the reeler gene (Reln) mutation. By comparison to non-ataxic controls, Dab1(scm) mutants showed severe motor coordination impairments on stationary beam, coat-hanger, and rotorod tests but were more active in the open-field. Dab1(scm) mutants were also less anxious in the elevated plus-maze but with higher latencies in the emergence test. In mutants versus controls, changes in regional brain metabolism as measured by cytochrome oxidase (COX) activity occurred mainly in structures intimately connected with the cerebellum, in basal ganglia, in limbic regions, particularly hippocampus, as well as in visual and parietal sensory cortices. Although behavioral results characterized a major cerebellar disorder in the Dab1(scm) mutants, motor activity impairments in the open-field were associated with COX activity changes in efferent basal ganglia structures such as the substantia nigra, pars reticulata. Metabolic changes in this structure were also associated with the anxiety changes observed in the elevated plus-maze and emergence test. These results indicate a crucial participation of the basal ganglia in the functional phenotype of ataxic Dab1(scm) mutants.

  18. Functional Connectivity Abnormalities of Brain Regions with Structural Deficits in Young Adult Male Smokers

    Science.gov (United States)

    Bu, Limei; Yu, Dahua; Su, Shaoping; Ma, Yao; von Deneen, Karen M.; Luo, Lin; Zhai, Jinquan; Liu, Bo; Cheng, Jiadong; Guan, Yanyan; Li, Yangding; Bi, Yanzhi; Xue, Ting; Lu, Xiaoqi; Yuan, Kai

    2016-01-01

    Smoking is one of the most prevalent dependence disorders. Previous studies have detected structural and functional deficits in smokers. However, few studies focused on the changes of resting state functional connectivity (RSFC) of the brain regions with structural deficits in young adult smokers. Twenty-six young adult smokers and 26 well-matched healthy non-smokers participated in our study. Voxel-based morphometry (VBM) and RSFC were employed to investigate the structural and functional changes in young adult smokers. Compared with healthy non-smokers, young smokers showed increased gray matter (GM) volume in the left putamen and decreased GM volume in the left anterior cingulate cortex (ACC). Moreover, GM volume in the left ACC has a negative correlation trend with pack-years and GM volume in the left putamen was positively correlated with pack-years. The left ACC and putamen with abnormal volumes were chosen as the regions of interest (ROIs) for the RSFC analysis. We found that smokers showed increased RSFC between the left ACC and right amygdala and between the left putamen and right anterior insula. We revealed structural and functional deficits within the frontostriatal circuits in young smokers, which may shed new insights into the neural mechanisms of smoking.

  19. Pedunculopontine Nucleus Region Deep Brain Stimulation in Parkinson Disease: Surgical Anatomy and Terminology

    Science.gov (United States)

    Hamani, Clement; Aziz, Tipu; Bloem, Bastiaan R.; Brown, Peter; Chabardes, Stephan; Coyne, Terry; Foote, Kelly; Garcia-Rill, Edgar; Hirsch, Etienne C.; Lozano, Andres M.; Mazzone, Paolo A.M.; Okun, Michael S.; Hutchison, William; Silburn, Peter; Zrinzo, Ludvic; Alam, Mesbah; Goetz, Laurent; Pereira, Erlick; Rughani, Anand; Thevathasan, Wesley; Moro, Elena; Krauss, Joachim K.

    2017-01-01

    Several lines of evidence over the last few years have been important in ascertaining that the pedunculopontine nucleus (PPN) region could be considered as a potential target for deep brain stimulation (DBS) to treat freezing and other problems as part of a spectrum of gait disorders in Parkinson disease and other akinetic movement disorders. Since the introduction of PPN DBS, a variety of clinical studies have been published. Most indicate improvements in freezing and falls in patients who are severely affected by these problems. The results across patients, however, have been variable, perhaps reflecting patient selection, heterogeneity in target selection and differences in surgical methodology and stimulation settings. Here we outline both the accumulated knowledge and the domains of uncertainty in surgical anatomy and terminology. Specific topics were assigned to groups of experts, and this work was accumulated and reviewed by the executive committee of the working group. Areas of disagreement were discussed and modified accordingly until a consensus could be reached. We demonstrate that both the anatomy and the functional role of the PPN region need further study. The borders of the PPN and of adjacent nuclei differ when different brainstem atlases and atlas slices are compared. It is difficult to delineate precisely the PPN pars dissipata from the nucleus cuneiformis, as these structures partially overlap. This lack of clarity contributes to the difficulty in targeting and determining the exact localization of the electrodes implanted in patients with akinetic gait disorders. Future clinical studies need to consider these issues. PMID:27723662

  20. DIFFERENTIAL EFFECTS OF INTRAUTERINE GROWTH RESRICTION ON THE REGIONAL NEUROCHEMICAL PROFILE OF THE DEVELOPING RAT BRAIN

    Science.gov (United States)

    Maliszewski-Hall, Anne M.; Alexander, Michelle; Tkáč, Ivan; Öz, Gülin; Rao, Raghavendra

    2016-01-01

    Background Intrauterine growth restricted (IUGR) infants are at increased risk for neurodevelopmental deficits that suggest the hippocampus and cerebral cortex may be particularly vulnerable. Objective Evaluate regional neurochemical profiles in IUGR and normally grown (NG) 7-day old rat pups using in vivo 1H magnetic resonance (MR) spectroscopy at 9.4T. Methods IUGR was induced via bilateral uterine artery ligation at gestational day 19 in pregnant Sprague Dawley dams. MR spectra were obtained from the cerebral cortex, hippocampus and striatum at P7 in IUGR (N=12) and NG (N=13) rats. Results In the cortex, IUGR resulted in lower concentrations of phosphocreatine, glutathione, taurine, total choline, total creatine (P<0.01) and [glutamate]/[glutamine] ratio (P <0.05). Lower taurine concentrations were observed in the hippocampus (P<0.01) and striatum (P <0.05). Conclusion IUGR differentially affects the neurochemical profile of the P7 rat brain regions. Persistent neurochemical changes may lead to cortex-based long-term neurodevelopmental deficits in human IUGR infants. PMID:25972040

  1. 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.

  2. Selenotranscriptomic Analyses Identify Signature Selenoproteins in Brain Regions in a Mouse Model of Parkinson’s Disease

    Science.gov (United States)

    Zhu, Hui; Sun, Sheng-Nan; Zheng, Jing; Fan, Hui-Hui; Wu, Hong-Mei; Chen, Song-Fang; Cheng, Wen-Hsing; Zhu, Jian-Hong

    2016-01-01

    Genes of selenoproteome have been increasingly implicated in various aspects of neurobiology and neurological disorders, but remain largely elusive in Parkinson’s disease (PD). In this study, we investigated the selenotranscriptome (24 selenoproteins in total) in five brain regions (cerebellum, substantia nigra, cortex, pons and hippocampus) by real time qPCR in a two-phase manner using a mouse model of chronic PD. A wide range of changes in selenotranscriptome was observed in a manner depending on selenoproteins and brain regions. While Selv mRNA was not detectable and Dio1& 3 mRNA levels were not affected, 1, 11 and 9 selenoproteins displayed patterns of increase only, decrease only, and mixed response, respectively, in these brain regions of PD mice. In particular, the mRNA expression of Gpx1-4 showed only a decreased trend in the PD mouse brains. In substantia nigra, levels of 17 selenoprotein mRNAs were significantly decreased whereas no selenoprotein was up-regulated in the PD mice. In contrast, the majority of selenotranscriptome did not change and a few selenoprotein mRNAs that respond displayed a mixed pattern of up- and down-regulation in cerebellum, cortex, hippocampus, and/or pons of the PD mice. Gpx4, Sep15, Selm, Sepw1, and Sepp1 mRNAs were most abundant across all these five brain regions. Our results showed differential responses of selenoproteins in various brain regions of the PD mouse model, providing critical selenotranscriptomic profiling for future functional investigation of individual selenoprotein in PD etiology. PMID:27656880

  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. 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.

  5. Functional connectivity between parietal and frontal brain regions and intelligence in young children: the Generation R study.

    Science.gov (United States)

    Langeslag, Sandra J E; Schmidt, Marcus; Ghassabian, Akhgar; Jaddoe, Vincent W; Hofman, Albert; van der Lugt, Aad; Verhulst, Frank C; Tiemeier, Henning; White, Tonya J H

    2013-12-01

    It has been shown in adults that individual differences in intelligence are related to the integrity of the interaction between parietal and frontal brain regions. Since connectivity between distant brain regions strengthens during childhood, it is unclear when in the course of development this relationship emerges. Thus, the goal of this study was to determine whether parietal-frontal functional connectivity is associated with intelligence in young children. We performed independent component analyses on resting-state fMRI data of 115 children (6-8 years old) to select seed and target regions for a seed/target region correlation analysis. We found that higher nonverbal intelligence was associated with increased functional connectivity between right parietal and right frontal regions, and between right parietal and dorsal anterior cingulate regions. The association between intelligence and functional connectivity between certain brain regions was stronger in girls than boys. In conclusion, we found that connectivity between the parietal and frontal lobes is critically involved in intelligence in young children. Copyright © 2012 Wiley Periodicals, Inc.

  6. Gamma knife radiosurgery for arteriovenous malformations located in eloquent regions of the brain

    Directory of Open Access Journals (Sweden)

    Javalkar Vijayakumar

    2009-12-01

    Full Text Available Background : Stereotactic radiosurgery is an effective treatment strategy for selected group of patients with cerebral arteriovenous malformations (AVMs. Aim : The aim of this study was to evaluate the obliteration rates, complications, and patient outcomes after Gamma knife radiosurgery for cerebral arteriovenous malformations (AVMs located in eloquent regions of the brain with an emphasis on neurological morbidity. Materials and Methods : Between 2000 and December 2005, 37 patients with AVMs in eloquent locations (sensory, motor, speech, visual cortex, basal ganglia, and brain stem underwent stereotactic radiosurgery. We retrospectively reviewed the clinical data of these patients to asses the outcomes. Of the 37 patients, only two patients had prior embolization. Three underwent prospective staged volume radiosurgery. Two patients needed redo-radiosurgery for residual AVM. Mean target volume was 9.1 cc. Three lesions had nidus volume more than 20 cc. Average marginal dose was 18.75 Gy. The median duration of follow-up was 23 months (range, 6-60 months. 15 patients had follow-up of more than 36 months. Results : A total of 15 patients had follow-up of more than 36 months, thus available for evaluation of angiographic obliteration rates. Complete angiographic obliteration was documented in seven patients (46.7%. Four patients experienced hemorrhage during the latency period. One patient who had subsequent hemorrhage on follow-up developed worsening of neurological deficit. One patient developed significant sensory symptoms which resolved after steroids. No additional clinical deterioration related to treatment was noted in rest of the patients. Conclusions : AVMs located in eloquent and in deep locations can be treated safely with stereotactic radiosurgery with acceptable obliteration rates and minimal morbidity.

  7. Effects of baseline CSF α-synuclein on regional brain atrophy rates in healthy elders, mild cognitive impairment and Alzheimer's disease.

    Directory of Open Access Journals (Sweden)

    Niklas Mattsson

    Full Text Available BACKGROUND: Cerebrospinal fluid (CSF α-synuclein is reduced in synucleinopathies, including dementia with Lewy bodies, and some studies have found increased CSF α-synuclein in Alzheimer's disease (AD. No study has explored effects of CSF α-synuclein on brain atrophy. Here we tested if baseline CSF α-synuclein affects brain atrophy rates and if these effects vary across brain regions, and across the cognitive spectrum from healthy elders (NL, to patients with mild cognitive impairment (MCI and AD. METHODS: Baseline CSF α-synuclein measurements and longitudinal structural brain magnetic resonance imaging was performed in 74 NL, 118 MCI patients and 55 AD patients. Effects of baseline CSF α-synuclein on regional atrophy rates were tested in 1 four pre-hoc defined regions possibly associated with Lewy body and/or AD pathology (amygdala, caudate, hippocampus, brainstem, and 2 all available regions of interest. Differences across diagnoses were tested by assessing the interaction of CSF α-synuclein and diagnosis (testing NL versus MCI, and NL versus AD. RESULTS: The effects of CSF α-synuclein on longitudinal atrophy rates were not significant after correction for multiple comparisons. There were tendencies for effects in AD in caudate (higher atrophy rates in subjects with higher CSF α-synuclein, P=0.046 and brainstem (higher atrophy rates in subjects with lower CSF α-synuclein, P=0.063. CSF α-synuclein had significantly different effects on atrophy rates in NL and AD in brainstem (P=0.037 and caudate (P=0.006. DISCUSSION: With the possible exception of caudate and brainstem, the overall weak effects of CSF α-synuclein on atrophy rates in NL, MCI and AD argues against CSF α-synuclein as a biomarker related to longitudinal brain atrophy in these diagnostic groups. Any effects of CSF α-synuclein may be attenuated by possible simultaneous occurrence of AD-related neuronal injury and concomitant Lewy body pathology, which may elevate and

  8. 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

  9. Functional connectivity between brain regions involved in learning words of a new language.

    Science.gov (United States)

    Veroude, Kim; Norris, David G; Shumskaya, Elena; Gullberg, Marianne; Indefrey, Peter

    2010-04-01

    Previous studies have identified several brain regions that appear to be involved in the acquisition of novel word forms. Standard word-by-word presentation is often used although exposure to a new language normally occurs in a natural, real world situation. In the current experiment we investigated naturalistic language exposure and applied a model-free analysis for hemodynamic-response data. Functional connectivity, temporal correlations between hemodynamic activity of different areas, was assessed during rest before and after presentation of a movie of a weather report in Mandarin Chinese to Dutch participants. We hypothesized that learning of novel words might be associated with stronger functional connectivity of regions that are involved in phonological processing. Participants were divided into two groups, learners and non-learners, based on the scores on a post hoc word recognition task. The learners were able to recognize Chinese target words from the weather report, while the non-learners were not. In the first resting state period, before presentation of the movie, stronger functional connectivity was observed for the learners compared to the non-learners between the left supplementary motor area and the left precentral gyrus as well as the left insula and the left rolandic operculum, regions that are important for phonological rehearsal. After exposure to the weather report, functional connectivity between the left and right supramarginal gyrus was stronger for learners than for non-learners. This is consistent with a role of the left supramarginal gyrus in the storage of phonological forms. These results suggest both pre-existing and learning-induced differences between the two groups.

  10. The Effect of an Experimental Missile Wound to the Brain on Brain Electrolytes, Regional Cerebral Blood Flow and Blood Brain Barrier Permeability.

    Science.gov (United States)

    1987-02-10

    In animals that we planned to measure intracranial pressure, we extended the scalp incision posteriorly and made a 5mm left occipital trephine to...with monitoring include trephination (even though the skull hole was sealed Vith dental acrylic) and the volume of the air-filled monitor itself. The...from these findings: 1) Brain wounds have been made through skull trephine openings in several prior experimental studies.(7- 15) Quite possibly brain

  11. Mercuric chloride-induced reactive oxygen species and its effect on antioxidant enzymes in different regions of rat brain.

    Science.gov (United States)

    Hussain, S; Rodgers, D A; Duhart, H M; Ali, S F

    1997-05-01

    The present study was undertaken to determine if in vitro exposure to mercuric chloride produces reactive oxygen species (ROS) in the synaptosomes prepared from various regions of rat brain. The effects of in vivo exposure to mercury on antioxidant enzymes such as superoxide dismutase (SOD) and glutathione peroxidase (GPx) activities in different regions of rat brain were also investigated. Adult male Sprague-Dawley (CD) rats were dosed with 0, 1, 2.0 or 4.0 mg HgCl2/kg body weight, for 7 days. One week after the last dose, animals were sacrificed by decapitation, their brains were removed and dissected and frozen in dry ice prior to measuring the activities of these enzymes. The results demonstrated that in vitro exposure to mercury produced a concentration-dependent increase of ROS in different regions of the rat brain. In vivo exposure to mercury produced a significant decrease of total SOD, Cu, Zn-SOD and Mn-SOD activities in the cerebellum of rats treated with different doses of mercury. SOD activity did not vary significantly in cerebral cortex and brain stem. GPx activity declined in a dose-dependent manner in the cerebellum with a significant reduction in animals receiving the 4 mg HgCl2/kg body weight. The activity of GPx increased in the brain stem while unchanged in the cerebral cortex. The results demonstrate that inorganic mercury decreased SOD activity significantly in the cerebellum while GPx activity was affected in both cerebellum and brain stem. Therefore, it can be concluded that oxidative stress may contribute to the development of neurodegenerative disorders caused by mercury intoxication.

  12. Ethics of the electrified mind: defining issues and perspectives on the principled use of brain stimulation in medical research and clinical care.

    Science.gov (United States)

    Cabrera, Laura Y; Evans, Emily L; Hamilton, Roy H

    2014-01-01

    In recent years, non-pharmacologic approaches to modifying human neural activity have gained increasing attention. One of these approaches is brain stimulation, which involves either the direct application of electrical current to structures in the nervous system or the indirect application of current by means of electromagnetic induction. Interventions that manipulate the brain have generally been regarded as having both the potential to alleviate devastating brain-related conditions and the capacity to create unforeseen and unwanted consequences. Hence, although brain stimulation techniques offer considerable benefits to society, they also raise a number of ethical concerns. In this paper we will address various dilemmas related to brain stimulation in the context of clinical practice and biomedical research. We will survey current work involving deep brain stimulation, transcranial magnetic stimulation and transcranial direct current stimulation. We will reflect upon relevant similarities and differences between them, and consider some potentially problematic issues that may arise within the framework of established principles of medical ethics: nonmaleficence and beneficence, autonomy, and justice.

  13. Duplication 12p and Pallister-Killian syndrome: a case report and review of the literature toward defining a Pallister-Killian syndrome minimal critical region.

    Science.gov (United States)

    Izumi, Kosuke; Conlin, Laura K; Berrodin, Donna; Fincher, Christopher; Wilkens, Alisha; Haldeman-Englert, Chad; Saitta, Sulagna C; Zackai, Elaine H; Spinner, Nancy B; Krantz, Ian D

    2012-12-01

    Pallister-Killian syndrome (PKS) is a multisystem sporadic genetic condition characterized by facial anomalies, variable developmental delay and intellectual impairment, hypotonia, hearing loss, seizures, pigmentary skin differences, temporal alopecia, diaphragmatic hernia, congenital heart defects, and other systemic abnormalities. PKS is typically caused by the presence of a supernumerary isochromosome composed of the short arms of chromosome 12 resulting in tetrasomy 12p, which is often present in a tissue limited mosaic state. The PKS phenotype has also often been observed in individuals with complete or partial duplications of 12p (trisomy 12p rather than tetrasomy 12p) as the result of an interstitial duplication or unbalanced translocation. We have identified a proposita with PKS who has two small de novo interstitial duplications of 12p which, along with a review of previously reported cases, has allowed us to define a minimum critical region for PKS.

  14. Chronic pain and evoked responses in the brain: A magnetoencephalographic study in Complex Regional Pain Syndrome I and II

    NARCIS (Netherlands)

    Theuvenet, P.J.

    2012-01-01

    Complex Regional Pain Syndrome (CRPS) type I and II are chronic pain syndromes with comparable symptoms, only in CRPS II a peripheral nerve injury is present. No objective tests are currently available to differentiate the two types which hampers diagnosis and treatment. Non-invasive brain imaging t

  15. 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.

  16. Define Project

    DEFF Research Database (Denmark)

    Munk-Madsen, Andreas

    2005-01-01

    "Project" is a key concept in IS management. The word is frequently used in textbooks and standards. Yet we seldom find a precise definition of the concept. This paper discusses how to define the concept of a project. The proposed definition covers both heavily formalized projects and informally...... organized, agile projects. Based on the proposed definition popular existing definitions are discussed....

  17. Algorithms of causal inference for the analysis of effective connectivity among brain regions

    Directory of Open Access Journals (Sweden)

    Daniel eChicharro

    2014-07-01

    Full Text Available In recent years, powerful general algorithms of causal inference have been developed. In particular, in the framework of Pearl’s causality, algorithms of inductive causation (IC and IC* provide a procedure to determine which causal connections among nodes in a network can be inferred from empirical observations even in the presence of latent variables, indicating the limits of what can be learned without active manipulation of the system. These algorithms can in principle become important complements to established techniques such as Granger causality and Dynamic Causal Modeling (DCM to analyze causal influences (effective connectivity among brain regions. However, their application to dynamic processes has not been yet examined. Here we study how to apply these algorithms to time-varying signals such as electrophysiological or neuroimaging signals. We propose a new algorithm which combines the basic principles of the previous algorithms with Granger causality to obtain a representation of the causal relations suited to dynamic processes. Furthermore, we use graphical criteria to predict dynamic statistical dependencies between the signals from the causal structure. We show how some problems for causal inference from neural signals (e.g. measurement noise, hemodynamic responses, and time aggregation can be understood in a general graphical approach. Focusing on the effect of spatial aggregation, we show that when causal inference is performed at a coarser scale than the one at which the neural sources interact, results strongly depend on the degree of integration of the neural sources aggregated in the signals, and thus characterize more the intra-areal properties than the interactions among regions. We finally discuss how the explicit consideration of latent processes contributes to understand Granger causality and DCM as well as to distinguish functional and effective connectivity.

  18. Algorithms of causal inference for the analysis of effective connectivity among brain regions.

    Science.gov (United States)

    Chicharro, Daniel; Panzeri, Stefano

    2014-01-01

    In recent years, powerful general algorithms of causal inference have been developed. In particular, in the framework of Pearl's causality, algorithms of inductive causation (IC and IC(*)) provide a procedure to determine which causal connections among nodes in a network can be inferred from empirical observations even in the presence of latent variables, indicating the limits of what can be learned without active manipulation of the system. These algorithms can in principle become important complements to established techniques such as Granger causality and Dynamic Causal Modeling (DCM) to analyze causal influences (effective connectivity) among brain regions. However, their application to dynamic processes has not been yet examined. Here we study how to apply these algorithms to time-varying signals such as electrophysiological or neuroimaging signals. We propose a new algorithm which combines the basic principles of the previous algorithms with Granger causality to obtain a representation of the causal relations suited to dynamic processes. Furthermore, we use graphical criteria to predict dynamic statistical dependencies between the signals from the causal structure. We show how some problems for causal inference from neural signals (e.g., measurement noise, hemodynamic responses, and time aggregation) can be understood in a general graphical approach. Focusing on the effect of spatial aggregation, we show that when causal inference is performed at a coarser scale than the one at which the neural sources interact, results strongly depend on the degree of integration of the neural sources aggregated in the signals, and thus characterize more the intra-areal properties than the interactions among regions. We finally discuss how the explicit consideration of latent processes contributes to understand Granger causality and DCM as well as to distinguish functional and effective connectivity.

  19. Altered Spontaneous Brain Activity in Cortical and Subcortical Regions in Parkinson’s Disease

    Directory of Open Access Journals (Sweden)

    Jie Xiang

    2016-01-01

    Full Text Available Purpose. The present study aimed to explore the changes of amplitude of low-frequency fluctuations (ALFF at rest in patients with Parkinson’s disease (PD. Methods. Twenty-four PD patients and 22 healthy age-matched controls participated in the study. ALFF was measured on the whole brain of all participants. A two-sample t-test was then performed to detect the group differences with age, gender, education level, head motion, and gray matter volume as covariates. Results. It was showed that PD patients had significantly decreased ALFF in the left thalamus/caudate and right insula/inferior prefrontal gyrus, whereas they had increased ALFF in the right medial prefrontal cortex (BA 8/6 and dorsolateral prefrontal cortex (BA 9/10. Conclusions. Our results indicated that significant alterations of ALFF in the subcortical regions and prefrontal cortex have been detected in PD patients, independent of age, gender, education, head motion, and structural atrophy. The current findings further provide insights into the biological mechanism of the disease.

  20. Long-term occupational stress is associated with regional reductions in brain tissue volumes.

    Directory of Open Access Journals (Sweden)

    Eva Blix

    Full Text Available There are increasing reports of cognitive and psychological declines related to occupational stress in subjects without psychiatric premorbidity or major life trauma. The underlying neurobiology is unknown, and many question the notion that the described disabilities represent a medical condition. Using PET we recently found that persons suffering from chronic occupational stress had limbic reductions in the 5-HT1A receptor binding potential. Here we examine whether chronic work-related stress is also associated with changes in brain structure. We performed MRI-based voxel-based morphometry and structural volumetry in stressed subjects and unstressed controls focusing on gray (GM and white matter (WM volumes, and the volumes of hippocampus, caudate, and putamen - structures known to be susceptible to neurotoxic changes. Stressed subjects exhibited significant reductions in the GM volumes of the anterior cingulate cortex and the dorsolateral prefrontal cortex. Furthermore, their caudate and putamen volumes were reduced, and the volumes correlated inversely to the degree of perceived stress. Our results add to previous data on chronic psychosocial stress, and indicate a morphological involvement of the frontostriatal circuits. The present findings of morphological changes in these regions confirm our previous conclusion that symptoms from occupational stress merit careful investigations and targeted treatment.

  1. Effects of reward sensitivity and regional brain volumes on substance use initiation in adolescence

    Science.gov (United States)

    Collins, Paul; Muetzel, Ryan; Schissel, Ann; Lim, Kelvin O.; Luciana, Monica

    2015-01-01

    This longitudinal study examines associations between baseline individual differences and developmental changes in reward [i.e. behavioral approach system (BAS)] sensitivity and relevant brain structures’ volumes to prospective substance use initiation during adolescence. A community sample of adolescents ages 15–18 with no prior substance use was assessed for substance use initiation (i.e. initiation of regular alcohol use and/or any use of other substances) during a 2-year follow-up period and for alcohol use frequency in the last year of the follow-up. Longitudinal ‘increases’ in BAS sensitivity were associated with substance use initiation and increased alcohol use frequency during the follow-up. Moreover, adolescents with smaller left nucleus accumbens at baseline were more likely to initiate substance use during the follow-up period. This study provides support for the link between developmental increases in reward sensitivity and substance use initiation in adolescence. The study also emphasizes the potential importance of individual differences in volumes of subcortical regions and their structural development for substance use initiation during adolescence. PMID:24526186

  2. Regional distribution of methionine adenosyltransferase in rat brain as measured by a rapid radiochemical method

    Energy Technology Data Exchange (ETDEWEB)

    Hiemke, C.; Ghraf, R.

    1981-09-01

    The distribution of methionine adenosyltransferase (MAT) in the CNS of the rat was studied by use of a rapid, sensitive and specific radiochemical method. The S-adenosyl-(methyl-/sup 14/C)L-methionine ((/sup 14/C)SAM) generated by adenosyl transfer from ATP to (methyl-/sup 14/C)L-methionine is quantitated by use of a SAM-consuming transmethylation reaction. Catechol O-methyltransferase (COMT), prepared from rat liver, transfers the methyl-/sup 14/C group of SAM to 3,4-dihydroxybenzoic acid. The /sup 14/C-labelled methylation products, vanillic acid and isovanillic acid, are separated from unreacted methionine by solvent extraction and quantitated by liquid scintillation counting. Compared to other methods of MAT determination, which include separation of generated SAM from methionine by ion-exchange chromatography, the assay described exhibited the same high degree of specificity and sensitivity but proved to be less time consuming. MAT activity was found to be uniformly distributed between various brain regions and the pituitary gland of adult male rats. In the pineal gland the enzyme activity is about tenfold higher.

  3. Synaptic genes are extensively downregulated across multiple brain regions in normal human aging and Alzheimer's disease.

    Science.gov (United States)

    Berchtold, Nicole C; Coleman, Paul D; Cribbs, David H; Rogers, Joseph; Gillen, Daniel L; Cotman, Carl W

    2013-06-01

    Synapses are essential for transmitting, processing, and storing information, all of which decline in aging and Alzheimer's disease (AD). Because synapse loss only partially accounts for the cognitive declines seen in aging and AD, we hypothesized that existing synapses might undergo molecular changes that reduce their functional capacity. Microarrays were used to evaluate expression profiles of 340 synaptic genes in aging (20-99 years) and AD across 4 brain regions from 81 cases. The analysis revealed an unexpectedly large number of significant expression changes in synapse-related genes in aging, with many undergoing progressive downregulation across aging and AD. Functional classification of the genes showing altered expression revealed that multiple aspects of synaptic function are affected, notably synaptic vesicle trafficking and release, neurotransmitter receptors and receptor trafficking, postsynaptic density scaffolding, cell adhesion regulating synaptic stability, and neuromodulatory systems. The widespread declines in synaptic gene expression in normal aging suggests that function of existing synapses might be impaired, and that a common set of synaptic genes are vulnerable to change in aging and AD.

  4. CLINICAL STUDY OF ISCHEMIC PENUMBRA REGION IN BRAIN ELECTRICAL ACTIVITY MAPPING

    Institute of Scientific and Technical Information of China (English)

    Liu Qingrui; Liu Mingshun; Gu Lanjie; Mei Fengjun

    2000-01-01

    Department of Neurology, Fourth Affiliated Hospital. Hebei Medical University, Shijiazhuang ABSTRACT OBJETIVE To study features and clinical usage of ischemic penumbra region(IPR) in brain electrical activity mapping(BEAM).BACKGROUND To explore the functional improvement index of IPR untraumaticly. METH0DS 69 patients with acute cerebral infarction were divided into two groups according to different therapeutic time window--early treatment group( 32 cases, treatment in 12 hours)and contral group (37 cases, treatment in 12-72 hours).They were analysed in BEAM pre-and post-treatment Results: BEAM showed that the power of infarcted core was decreased and IPR became smaller in slow waves significantly after treatment in early treatment group and this change was in good agreement with improvement of clinical functions and SPECT DISCUSSION The key to treat acute cerebral infarction was to improve functions of IPR as 8oos as possible, BEAM could show the location and size of IPR. CONCLUSION BEAM was one of important index in evaluating the function of IPR.

  5. Effects of reward sensitivity and regional brain volumes on substance use initiation in adolescence.

    Science.gov (United States)

    Urošević, Snežana; Collins, Paul; Muetzel, Ryan; Schissel, Ann; Lim, Kelvin O; Luciana, Monica

    2015-01-01

    This longitudinal study examines associations between baseline individual differences and developmental changes in reward [i.e. behavioral approach system (BAS)] sensitivity and relevant brain structures' volumes to prospective substance use initiation during adolescence. A community sample of adolescents ages 15-18 with no prior substance use was assessed for substance use initiation (i.e. initiation of regular alcohol use and/or any use of other substances) during a 2-year follow-up period and for alcohol use frequency in the last year of the follow-up. Longitudinal 'increases' in BAS sensitivity were associated with substance use initiation and increased alcohol use frequency during the follow-up. Moreover, adolescents with smaller left nucleus accumbens at baseline were more likely to initiate substance use during the follow-up period. This study provides support for the link between developmental increases in reward sensitivity and substance use initiation in adolescence. The study also emphasizes the potential importance of individual differences in volumes of subcortical regions and their structural development for substance use initiation during adolescence.

  6. Combining data on health care utilization and socioeconomic status of a defined population: use of a population oriented health information system for regional planning.

    Science.gov (United States)

    Brommels, M; Heinonen, M O; Tuomola, S

    1987-01-01

    Health services planning on a regional or national level needs information on health care utilization as well as data on the population to be served. Health or hospital information systems usually cover services provision and utilization, and population data for planning purposes must be obtained from other sources. In the health information system presented, hospital performance data are combined with census and socioeconomic data of the population. That makes cautious analysis of reasons for variation in health care utilization within the planning area possible. The HIS is regional, including 11 health care providers, and population based, linking data to municipality (38 in all). The system is described, including its structure, input registration, file content and output formats. An output example is presented. Necessary conditions for use of the HIS in planning activities are that the corresponding health care delivery system is comprehensive, the population served well defined, and that good control of patient flow and user behaviour is achieved. Use is limited by the character of information stored in the HIS: it is registered retrospectively and by routine. In a system covering various hospitals and municipalities, engaging different types of clerical and health care personnel, data reliability is also a critical issue.

  7. 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

  8. Analysis of the protein network of cholesterol homeostasis in different brain regions: an age and sex dependent perspective.

    Science.gov (United States)

    Segatto, Marco; Di Giovanni, Annalaura; Marino, Maria; Pallottini, Valentina

    2013-07-01

    Although a great knowledge about the patho-physiological roles of cholesterol metabolism perturbation in several organs has been reached, scarce information is available on the regulation of cholesterol homeostasis in the brain where this lipid is involved in the maintenance of several of neuronal processes. Currently, no study is available in literature dealing how and if sex and age may modulate the major proteins involved in the regulatory network of cholesterol levels in different brain regions. Here, we investigated the behavior of 3-hydroxy 3-methylglutaryl coenzyme A reductase (HMGR) and low-density lipoprotein receptor (LDLr) in adult (3-month-old) and aged (12-month-old) male and female rats. The analyses were performed in four different brain regions: cortex, brain stem, hippocampus, and cerebellum which represent brain areas characterized by different neuronal cell types, metabolism, cytoarchitecture and white matter composition. The results show that in hippocampus HMGR is lower (30%) in adult female rats than in age-matched males. Differences in LDLr expression are also observable in old females with respect to age-matched males: the protein levels increase (40%) in hippocampus and decrease (20%) in cortex, displaying different mechanisms of regulation. The mechanism underlying the observed modifications are ascribable to Insig-1 and SREBP-1 modulation. The obtained data demonstrate that age- and sex-related differences in cholesterol homeostasis maintenance exist among brain regions, such as the hippocampus and the prefrontal cortex, important for learning, memory and affection. Some of these differences could be at the root of marked gender disparities observed in clinical disease incidence, manifestation, and prognosis.

  9. Sleep deprivation disturbed regional brain activity in healthy subjects: evidence from a functional magnetic resonance-imaging study

    Directory of Open Access Journals (Sweden)

    Wang L

    2016-04-01

    Full Text Available Li Wang, Yin Chen, Ying Yao, Yu Pan, Yi Sun Department of Neurology, Sir Run Run Shaw Hospital, School of Medicine, Zhejiang University, Hangzhou, People’s Republic of China Objective: The aim of this study was to use amplitude of low-frequency fluctuation (ALFF to explore regional brain activities in healthy subjects after sleep deprivation (SD.Materials and methods: A total of 16 healthy subjects (eight females, eight males underwent the session twice: once was after normal sleep (NS, and the other was after SD. ALFF was used to assess local brain features. The mean ALFF-signal values of the different brain areas were evaluated to investigate relationships with clinical features and were analyzed with a receiver-operating characteristic curve.Results: Compared with NS subjects, SD subjects showed a lower response-accuracy rate, longer response time, and higher lapse rate. Compared with NS subjects, SD subjects showed higher ALFF area in the right cuneus and lower ALFF area in the right lentiform nucleus, right claustrum, left dorsolateral prefrontal cortex, and left inferior parietal cortex. ALFF differences in regional brain areas showed high sensitivity and specificity. In the SD group, mean ALFF of the right claustrum showed a significant positive correlation with accuracy rate (r=0.687, P=0.013 and a negative correlation with lapse rate (r=-0.706, P=0.01. Mean ALFF of the dorsolateral prefrontal cortex showed a significant positive correlation with response time (r=0.675, P=0.016.Conclusion: SD disturbed the regional brain activity of the default-mode network, its anticorrelated “task-positive” network, and the advanced cognitive function brain areas. Keywords: sleep deprivation, amplitude of low-frequency fluctuation, default-mode network, functional magnetic resonance imaging

  10. Differences in regional brain volume related to the extraversion-introversion dimension--a voxel based morphometry study.

    Science.gov (United States)

    Forsman, Lea J; de Manzano, Orjan; Karabanov, Anke; Madison, Guy; Ullén, Fredrik

    2012-01-01

    Extraverted individuals are sociable, behaviorally active, and happy. We report data from a voxel based morphometry study investigating, for the first time, if regional volume in gray and white matter brain regions is related to extraversion. For both gray and white matter, all correlations between extraversion and regional brain volume were negative, i.e. the regions were larger in introverts. Gray matter correlations were found in regions that included the right prefrontal cortex and the cortex around the right temporo-parietal junction--regions that are known to be involved in behavioral inhibition, introspection, and social-emotional processing, e.g. evaluation of social stimuli and reasoning about the mental states of others. White matter correlations extended from the brainstem to widespread cortical regions, and were largely due to global effects, i.e. a larger total white matter volume in introverts. We speculate that these white matter findings may reflect differences in ascending modulatory projections affecting cortical regions involved in behavioral regulation.

  11. Application of machine learning methods to describe the effects of conjugated equine estrogens therapy on region-specific brain volumes.

    Science.gov (United States)

    Casanova, Ramon; Espeland, Mark A; Goveas, Joseph S; Davatzikos, Christos; Gaussoin, Sarah A; Maldjian, Joseph A; Brunner, Robert L; Kuller, Lewis H; Johnson, Karen C; Mysiw, W Jerry; Wagner, Benjamin; Resnick, Susan M

    2011-05-01

    Use of conjugated equine estrogens (CEE) has been linked to smaller regional brain volumes in women aged ≥65 years; however, it is unknown whether this results in a broad-based characteristic pattern of effects. Structural magnetic resonance imaging was used to assess regional volumes of normal tissue and ischemic lesions among 513 women who had been enrolled in a randomized clinical trial of CEE therapy for an average of 6.6 years, beginning at ages 65-80 years. A multivariate pattern analysis, based on a machine learning technique that combined Random Forest and logistic regression with L(1) penalty, was applied to identify patterns among regional volumes associated with therapy and whether patterns discriminate between treatment groups. The multivariate pattern analysis detected smaller regional volumes of normal tissue within the limbic and temporal lobes among women that had been assigned to CEE therapy. Mean decrements ranged as high as 7% in the left entorhinal cortex and 5% in the left perirhinal cortex, which exceeded the effect sizes reported previously in frontal lobe and hippocampus. Overall accuracy of classification based on these patterns, however, was projected to be only 54.5%. Prescription of CEE therapy for an average of 6.6 years is associated with lower regional brain volumes, but it does not induce a characteristic spatial pattern of changes in brain volumes of sufficient magnitude to discriminate users and nonusers. Copyright © 2011 Elsevier Inc. All rights reserved.

  12. 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.

  13. 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.

  14. Spontaneous mentalizing captures variability in the cortical thickness of social brain regions

    National Research Council Canada - National Science Library

    Rice, Katherine; Redcay, Elizabeth

    2015-01-01

    .... "In this story, what does Steve think Julia believes?"). Neuroanatomical measures may provide a way to explore the brain bases of individual differences in more naturalistic everyday mentalizing...

  15. The social network-network: size is predicted by brain structure and function in the amygdala and paralimbic regions.

    Science.gov (United States)

    Von Der Heide, Rebecca; Vyas, Govinda; Olson, Ingrid R

    2014-12-01

    The social brain hypothesis proposes that the large size of the primate neocortex evolved to support complex and demanding social interactions. Accordingly, recent studies have reported correlations between the size of an individual's social network and the density of gray matter (GM) in regions of the brain implicated in social cognition. However, the reported relationships between GM density and social group size are somewhat inconsistent with studies reporting correlations in different brain regions. One factor that might account for these discrepancies is the use of different measures of social network size (SNS). This study used several measures of SNS to assess the relationships SNS and GM density. The second goal of this study was to test the relationship between social network measures and functional brain activity. Participants performed a social closeness task using photos of their friends and unknown people. Across the VBM and functional magnetic resonance imaging analyses, individual differences in SNS were consistently related to structural and functional differences in three regions: the left amygdala, right amygdala and the right entorhinal/ventral anterior temporal cortex.

  16. Overlapping and non-overlapping brain regions for theory of mind and self reflection in individual subjects.

    Science.gov (United States)

    Saxe, Rebecca; Moran, Joseph M; Scholz, Jonathan; Gabrieli, John

    2006-12-01

    When subjects are required to reason about someone's false belief, a consistent pattern of brain regions are recruited including the medial prefrontal cortex, medial precuneus and bilateral temporo-parietal junction. Previous group analyses suggest that the two medial regions, but not the lateral regions, are also recruited when subjects engage in self-reflection. The current study directly compared the results of the 'false belief' and 'self' tasks in individual subjects. Consistent with previous reports, the medial prefrontal and medial precuneus regions recruited by the two tasks significantly overlap in individual subjects, although there was also evidence for non-overlapping voxels in medial regions. The temporo-parietal regions are only recruited for the 'theory of mind' task. Six possible models of the relationship between theory of mind, self-reflection and autobiographical memory, all consistent with both neurobiological and developmental evidence to date, are discussed.

  17. 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.

  18. Distribution of Non-Persistent Endocrine Disruptors in Two Different Regions of the Human Brain

    NARCIS (Netherlands)

    Meer, Thomas P van der; Artacho-Cordón, Francisco; Swaab, Dick F; Struik, Dicky; Makris, Konstantinos C; Wolffenbuttel, Bruce H R; Frederiksen, Hanne; Vliet-Ostaptchouk, Jana V van

    2017-01-01

    Non-persistent endocrine disrupting chemicals (npEDCs) can affect multiple organs and systems in the body. Whether npEDCs can accumulate in the human brain is largely unknown. The major aim of this pilot study was to examine the presence of environmental phenols and parabens in two distinct brain

  19. Distribution of Non-Persistent Endocrine Disruptors in Two Different Regions of the Human Brain

    DEFF Research Database (Denmark)

    van der Meer, Thomas P; Artacho-Cordón, Francisco; Swaab, Dick F

    2017-01-01

    Non-persistent endocrine disrupting chemicals (npEDCs) can affect multiple organs and systems in the body. Whether npEDCs can accumulate in the human brain is largely unknown. The major aim of this pilot study was to examine the presence of environmental phenols and parabens in two distinct brain...

  20. Influence of Punica granatum L. on region specific responses in rat brain during Alloxan-Induced diabetes

    Institute of Scientific and Technical Information of China (English)

    Sushil Kumar Middha; Talambedu Usha; Tekupalli RaviKiran

    2012-01-01

    Objective: The present study was carried out to investigate the effects of Punica granatum peel methanolic extract (PGPE) on cerebral cortex (CC) and Hippocampus (HC) brain antioxidant defense system and markers of lipid and protein oxidation in alloxan induced diabetic rats.Methods:Oral administration of PGPE (75 and 150 mg of kg body weight) for 45 days resulted in significant reduction in blood glucose levels. Results: Supplementation of diabetic rats with PGPE showed increased activities of SOD and GPx with concomitant decrease in MDA and PC content. Region-specific changes were more evident in the HC when compared to CC. Conclusions: The present study indicated that PGPE can ameliorate brain oxidative stress in alloxan induced diabetic rats by up regulating antioxidant defense mechanism by attenuating lipid and protein oxidation. PGPE thus may be used as a potential therapeutic agent in preventing diabetic complications in the brain.

  1. 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 hom...

  2. The effects of gender and depression severity on the association between alpha asymmetry and depression across four brain regions.

    Science.gov (United States)

    Jesulola, Emmanuel; Sharpley, Christopher F; Agnew, Linda L

    2017-03-15

    Data describing the association between EEG asymmetry and depression status have been equivocal. Effects from brain regions involved, depression severity, and the generalisability of findings across genders, have been inconsistently examined and/or verified. This study investigated these issues within a community sample to potentially expand the asymmetry hypothesis to non-severe depression participants. The singular effects of brain region and electrode site, gender, and depression severity, plus the interaction between gender and depression severity across brain regions were investigated in a study of alpha asymmetry among 46 males and 54 females (M age=32.5 yr, SD=14.13 yr) using the Self-rating Depression Scale (Zung, 1973). There was no significant difference across genders or age for depression severity. Dichotomous classification of depressed state produced similar but slightly different results from analysis of the whole range of depression status, although the frontal region was the only area where depression was consistently significantly associated with EEG asymmetry, and then only for females. However, the direction of those differences for females was opposite of that predicted by the EEG asymmetry-depression hypothesis. Several methodological issues that may have contributed to these findings are discussed, with suggestions made for future research that focusses upon individual depression symptom profiles rather than dichotomous or total depression scores in order to assist in developing a clinically-relevant model of EEG asymmetry in depressed persons.

  3. Neuropsin Expression Correlates with Dendritic Marker MAP2c Level in Different Brain Regions of Aging Mice.

    Science.gov (United States)

    Konar, Arpita; Thakur, M K

    2015-01-01

    Neuropsin (NP) is a serine protease, implicated in synaptic plasticity and memory acquisition through cleavage of synaptic adhesion molecule, L1CAM. However, NP has not been explored during brain aging that entails drastic deterioration of plasticity and memory with selective regional vulnerability. Therefore, we have analysed the expression of NP and correlated with its function via analysis of endogenous cleavage of L1CAM and level of dendritic marker MAP2c in different regions of the aging mouse brain. While NP expression gradually decreased in the cerebral cortex during aging, it showed a sharp rise in both olfactory bulb and hippocampus in adult and thereafter declined in old age. NP expression was moderate in young medulla, but undetectable in midbrain and cerebellum. It was positively correlated with L1CAM cleavage and MAP2c level in different brain regions during aging. Taken together, our study shows age-dependent regional variation in NP expression and its positive correlation with MAP2c level, suggesting the involvement of NP in MAP2c mediated alterations in dendritic morphology during aging.

  4. 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.)

  5. Intra-Amniotic LPS Induced Region-Specific Changes in Presynaptic Bouton Densities in the Ovine Fetal Brain

    Directory of Open Access Journals (Sweden)

    Eveline Strackx

    2015-01-01

    Full Text Available Rationale. Chorioamnionitis has been associated with increased risk for fetal brain damage. Although, it is now accepted that synaptic dysfunction might be responsible for functional deficits, synaptic densities/numbers after a fetal inflammatory challenge have not been studied in different regions yet. Therefore, we tested in this study the hypothesis that LPS-induced chorioamnionitis caused profound changes in synaptic densities in different regions of the fetal sheep brain. Material and Methods. Chorioamnionitis was induced by a 10 mg intra-amniotic LPS injection at two different exposure intervals. The fetal brain was studied at 125 days of gestation (term = 150 days either 2 (LPS2D group or 14 days (LPS14D group after LPS or saline injection (control group. Synaptophysin immunohistochemistry was used to quantify the presynaptic density in layers 2-3 and 5-6 of the motor cortex, somatosensory cortex, entorhinal cortex, and piriforme cortex, in the nucleus caudatus and putamen and in CA1/2, CA3, and dentate gyrus of the hippocampus. Results. There was a significant reduction in presynaptic bouton densities in layers 2-3 and 5-6 of the motor cortex and in layers 2-3 of the entorhinal and the somatosensory cortex, in the nucleus caudate and putamen and the CA1/2 and CA3 of the hippocampus in the LPS2D compared to control animals. Only in the motor cortex and putamen, the presynaptic density was significantly decreased in the LPS14 D compared to the control group. No changes were found in the dentate gyrus of the hippocampus and the piriforme cortex. Conclusion. We demonstrated that LPS-induced chorioamnionitis caused a decreased density in presynaptic boutons in different areas in the fetal brain. These synaptic changes seemed to be region-specific, with some regions being more affected than others, and seemed to be transient in some regions.

  6. Sexually dimorphic effects of catechol-O-methyltransferase (COMT inhibition on dopamine metabolism in multiple brain regions.

    Directory of Open Access Journals (Sweden)

    Linda M Laatikainen

    Full Text Available The catechol-O-methyltransferase (COMT enzyme metabolises catecholamines. COMT inhibitors are licensed for the adjunctive treatment of Parkinson's disease and are attractive therapeutic candidates for other neuropsychiatric conditions. COMT regulates dopamine levels in the prefrontal cortex (PFC but plays a lesser role in the striatum. However, its significance in other brain regions is largely unknown, despite its links with a broad range of behavioural phenotypes hinting at more widespread effects. Here, we investigated the effect of acute systemic administration of the brain-penetrant COMT inhibitor tolcapone on tissue levels of dopamine, noradrenaline, and the dopamine metabolites 3,4-dihydroxyphenylacetic acid (DOPAC and homovanillic acid (HVA. We examined PFC, striatum, hippocampus and cerebellum in the rat. We studied both males and females, given sexual dimorphisms in several aspects of COMT's function. Compared with vehicle, tolcapone significantly increased dopamine levels in the ventral hippocampus, but did not affect dopamine in other regions, nor noradrenaline in any region investigated. Tolcapone increased DOPAC and/or decreased HVA in all brain regions studied. Notably, several of the changes in DOPAC and HVA, particularly those in PFC, were more prominent in females than males. These data demonstrate that COMT alters ventral hippocampal dopamine levels, as well as regulating dopamine metabolism in all brain regions studied. They demonstrate that COMT is of significance beyond the PFC, consistent with its links with a broad range of behavioural phenotypes. Furthermore, they suggest that the impact of tolcapone may be greater in females than males, a finding which may be of clinical significance in terms of the efficacy and dosing of COMT inhibitors.

  7. Regional distributions of manganese, iron, copper, and zinc in the brains of 6-hydroxydopamine-induced parkinsonian rats.

    Science.gov (United States)

    Tarohda, Tohru; Ishida, Yasushi; Kawai, Keiichi; Yamamoto, Masayoshi; Amano, Ryohei

    2005-09-01

    Time courses of changes in manganese, iron, copper, and zinc concentrations were examined in regions of the brain of a 6-hydroxydopamine (6-OHDA)-induced rat model of Parkinson's disease using inductively coupled plasma mass spectrometry (ICP-MS). The concentrations were simultaneously determined in brain section at the level of the substantia nigra 1, 3, 7, 10, 14, and 21 days after the 6-OHDA treatment and compared with those of control rats. The distributions of these elements were obtained for 18 regions of the sagittal section (1-mm thick). The ICP-MS results indicated that Mn, Fe, Cu, and Zn levels of the 6-OHDA-induced parkinsonian brain were observed to increase in all regions that lay along the dopaminergic pathway. In the substantia nigra, the increase in Mn level occurred rapidly from 3 to 7 days and preceded those in the other elements, reaching a plateau in the 6-OHDA brain. Iron and Zn levels increased gradually until 7 days and then increased rapidly from 7 to 10 days. The increase in the copper level was slightly delayed. In other regions, such as the globus pallidus, putamen, and amygdala, the levels of Mn, Fe, Cu, and Zn increased with time after 6-OHDA treatment, although the time courses of their changes were region-specific. These findings contribute to our understanding of the roles of Mn and Fe in the induction of neurological symptoms and progressive loss of dopaminergic neurons in the development of Parkinson's disease. Manganese may hold the key to disturbing cellular Fe homeostasis and accelerating Fe levels, which play the most important role in the development of Parkinson's disease.

  8. Sustained spatial attention to vibrotactile stimulation in the flutter range: relevant brain regions and their interaction.

    Science.gov (United States)

    Goltz, Dominique; Pleger, Burkhard; Thiel, Sabrina D; Thiel, Sabrina; Villringer, Arno; Müller, Matthias M

    2013-01-01

    The present functional magnetic resonance imaging (fMRI) study was designed to get a better understanding of the brain regions involved in sustained spatial attention to tactile events and to ascertain to what extent their activation was correlated. We presented continuous 20 Hz vibrotactile stimuli (range of flutter) concurrently to the left and right index fingers of healthy human volunteers. An arrow cue instructed subjects in a trial-by-trial fashion to attend to the left or right index finger and to detect rare target events that were embedded in the vibrotactile stimulation streams. We found blood oxygen level-dependent (BOLD) attentional modulation in primary somatosensory cortex (SI), mainly covering Brodmann area 1, 2, and 3b, as well as in secondary somatosensory cortex (SII), contralateral to the to-be-attended hand. Furthermore, attention to the right (dominant) hand resulted in additional BOLD modulation in left posterior insula. All of the effects were caused by an increased activation when attention was paid to the contralateral hand, except for the effects in left SI and insula. In left SI, the effect was related to a mixture of both a slight increase in activation when attention was paid to the contralateral hand as well as a slight decrease in activation when attention was paid to the ipsilateral hand (i.e., the tactile distraction condition). In contrast, the effect in left posterior insula was exclusively driven by a relative decrease in activation in the tactile distraction condition, which points to an active inhibition when tactile information is irrelevant. Finally, correlation analyses indicate a linear relationship between attention effects in intrahemispheric somatosensory cortices, since attentional modulation in SI and SII were interrelated within one hemisphere but not across hemispheres. All in all, our results provide a basis for future research on sustained attention to continuous vibrotactile stimulation in the range of flutter.

  9. Sustained spatial attention to vibrotactile stimulation in the flutter range: relevant brain regions and their interaction.

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    Dominique Goltz

    Full Text Available The present functional magnetic resonance imaging (fMRI study was designed to get a better understanding of the brain regions involved in sustained spatial attention to tactile events and to ascertain to what extent their activation was correlated. We presented continuous 20 Hz vibrotactile stimuli (range of flutter concurrently to the left and right index fingers of healthy human volunteers. An arrow cue instructed subjects in a trial-by-trial fashion to attend to the left or right index finger and to detect rare target events that were embedded in the vibrotactile stimulation streams. We found blood oxygen level-dependent (BOLD attentional modulation in primary somatosensory cortex (SI, mainly covering Brodmann area 1, 2, and 3b, as well as in secondary somatosensory cortex (SII, contralateral to the to-be-attended hand. Furthermore, attention to the right (dominant hand resulted in additional BOLD modulation in left posterior insula. All of the effects were caused by an increased activation when attention was paid to the contralateral hand, except for the effects in left SI and insula. In left SI, the effect was related to a mixture of both a slight increase in activation when attention was paid to the contralateral hand as well as a slight decrease in activation when attention was paid to the ipsilateral hand (i.e., the tactile distraction condition. In contrast, the effect in left posterior insula was exclusively driven by a relative decrease in activation in the tactile distraction condition, which points to an active inhibition when tactile information is irrelevant. Finally, correlation analyses indicate a linear relationship between attention effects in intrahemispheric somatosensory cortices, since attentional modulation in SI and SII were interrelated within one hemisphere but not across hemispheres. All in all, our results provide a basis for future research on sustained attention to continuous vibrotactile stimulation in the range

  10. Selective plasticity of hippocampal GABAergic interneuron populations following kindling of different brain regions.

    Science.gov (United States)

    Botterill, J J; Nogovitsyn, N; Caruncho, H J; Kalynchuk, L E

    2017-02-01

    The vulnerability and plasticity of hippocampal GABAergic interneurons is a topic of broad interest and debate in the field of epilepsy. In this experiment,