WorldWideScience

Sample records for brain region mentions

  1. Automated recognition of brain region mentions in neuroscience literature

    Directory of Open Access Journals (Sweden)

    Leon French

    2009-09-01

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

  2. Brain Region Mapping using Global Metabolomics

    Science.gov (United States)

    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

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

    Science.gov (United States)

    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

  4. 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...

  5. Should ESL Classes Never Mention Religion?

    Institute of Scientific and Technical Information of China (English)

    顾炜俊

    2014-01-01

    As religion is an integrated part of human history and culture, an L2 cannot be learnt without some mentioning of it in the language classes. Teaching about religion cannot only help L2 learners learn the L2 itself but other general knowledge such as history, music and arts. However, differences should be made between teaching religion and teaching about religion and some guidelines should be followed if teachers are to teach it in the language classes.

  6. 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...

  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. 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.

  9. 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

  10. 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.

  11. 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...

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

    Science.gov (United States)

    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.

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

    Energy Technology Data Exchange (ETDEWEB)

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

    2005-02-01

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

  14. 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

  15. 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.

  16. 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.

  17. 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.

  18. 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.

  19. 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.

  20. Automated regional behavioral analysis for human brain images.

    Science.gov (United States)

    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.

  1. 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.

  2. 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.

  3. 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

  4. 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.

  5. 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.…

  6. 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.…

  7. 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.

  8. 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.

  9. 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...

  10. Overview of BioCreative II gene mention recognition

    NARCIS (Netherlands)

    Smith, L.; Tanabe, L.K.; Johnson, R.; Kuo, C.-J.; Chung, I-F.; Hsu, C.-N.; Lin, Y.-S.; Klinger, R.; Friedrich, C.M.; Ganchev, K.; Torii, M.; Liu, H.; Haddow, B.; Struble, C.A.; Povinelli, R.J.; Vlachos, A.; Baumgartner (jr.), W.A.; Hunter, L.; Carpenter, B.; Tsai, R.T.-H.; Dai, H.-J.; Liu, F.; Chen, Y.; Sun, C.; Katrenko, S.; Adriaans, P.; Blaschke, C.; Torres, R.; Neves, M.; Nakov, P.; Divoli, A.; Maña-López, M.; Mata, J.; Wilbur, W.J.

    2008-01-01

    Nineteen teams presented results for the Gene Mention Task at the BioCreative II Workshop. In this task participants designed systems to identify substrings in sentences corresponding to gene name mentions. A variety of different methods were used and the results varied with a highest achieved F1

  11. 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...

  12. 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.

  13. 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.

  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. 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.

  20. 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.

  1. Honorable Mention: Donald F. Klein Early Career Investigator Award

    Science.gov (United States)

    Klumpp, Heide; Ho, S. Shaun; Taylor, Stephan F.; Phan, K. Luan; Abelson, James L.; Liberzon, Israel

    2015-01-01

    Background Individuals vary in the degree to which salient threatening stimuli disrupt or distract from goal-directed cognitive processes. Excessive attention to threat or difficulty resolving the interference created by threat cues could contribute to anxious psychopathology; disruptions in frontal brain regions implicated in attentional control or resolution of emotional interference (e.g. anterior cingulate cortex, “ACC”) might play a role. In this study, we explored the hypothesis that trait anxiety would be associated with ACC activity in an attentional control task with varying levels of threat interference. Methods During functional magnetic resonance imaging, 20 healthy individuals who varied in trait anxiety levels viewed angry, fearful, and neutral faces superimposed on an indoor or outdoor scene. In a high-threat interference condition, subjects identified the gender of the face (Attend Face). In a low-threat interference condition, they identified the scene type (Attend Scene). Whole-brain analysis was used to compare Attend Face with Attend Scene for angry and fearful (versus neutral) faces. Contrasts were correlated with trait anxiety level. Results Behavioral data confirmed that Attend Face produced greater threat interference than Attend Scene. Brain imaging results showed that trait anxiety was inversely associated with bilateral rostral ACC activity for Attend Face relative to Attend Scene for angry faces. A similar relationship was not seen for fearful faces. Conclusions The rostral ACC is implicated in assessing the salience of emotional information and controlling attention to resolve emotional interference. The link between higher trait anxiety and decreased ACC activation for angry faces suggests reduced attentional control for signals of interpersonal threat in healthy anxiety-prone individuals. PMID:21394852

  2. 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

  3. 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.

  4. 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.

  5. 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

  6. 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.

  7. 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.

  8. Overview of BioCreative II gene mention recognition.

    Science.gov (United States)

    Smith, Larry; Tanabe, Lorraine K; Ando, Rie Johnson nee; Kuo, Cheng-Ju; Chung, I-Fang; Hsu, Chun-Nan; Lin, Yu-Shi; Klinger, Roman; Friedrich, Christoph M; Ganchev, Kuzman; Torii, Manabu; Liu, Hongfang; Haddow, Barry; Struble, Craig A; Povinelli, Richard J; Vlachos, Andreas; Baumgartner, William A; Hunter, Lawrence; Carpenter, Bob; Tsai, Richard Tzong-Han; Dai, Hong-Jie; Liu, Feng; Chen, Yifei; Sun, Chengjie; Katrenko, Sophia; Adriaans, Pieter; Blaschke, Christian; Torres, Rafael; Neves, Mariana; Nakov, Preslav; Divoli, Anna; Maña-López, Manuel; Mata, Jacinto; Wilbur, W John

    2008-01-01

    Nineteen teams presented results for the Gene Mention Task at the BioCreative II Workshop. In this task participants designed systems to identify substrings in sentences corresponding to gene name mentions. A variety of different methods were used and the results varied with a highest achieved F1 score of 0.8721. Here we present brief descriptions of all the methods used and a statistical analysis of the results. We also demonstrate that, by combining the results from all submissions, an F score of 0.9066 is feasible, and furthermore that the best result makes use of the lowest scoring submissions.

  9. 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.

  10. Giving good directions: order of mention reflects visual salience

    Directory of Open Access Journals (Sweden)

    Alasdair Daniel Francis Clarke

    2015-12-01

    Full Text Available In complex stimuli, there are many different possible ways to refer to a specified target. Previousstudies have shown that when people are faced with such a task, the content of their referringexpression reflects visual properties such as size, salience and clutter. Here, we extend thesefindings and present evidence that (i the influence of visual perception on sentence constructiongoes beyond content selection and in part determines the order in which different objects arementioned and (ii order of mention influences comprehension. Study 1 (a corpus study ofreference productions shows that when a speaker uses a relational description to mention asalient object, that object is treated as being in the common ground and is more likely to bementioned first. Study 2 (a visual search study asks participants to listen to referring expressionsand find the specified target; in keeping with the above result, we find that search for easy-to-findtargets is faster when the target is mentioned first, while search for harder-to-find targets isfacilitated by mentioning the target later, after a landmark in a relational description. Our findingsshow that seemingly low-level and disparate mental modules like perception and sentenceplanning interact at a high level and in task-dependent ways.

  11. 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.

  12. 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.

  13. 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.

  14. 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.

  15. 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

  16. 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...

  17. Health-Promoting Verses as mentioned in the Holy Quran.

    Science.gov (United States)

    Aboul-Enein, Basil H

    2016-06-01

    The Quran is regarded as both the spiritual and behavioral guidance for all Muslims. This narrative study was designed at examining relevant health-promoting verses in the Quran and to identify the chapters and verses where keywords and phrases are mentioned relevant to health promotion and behavior. Twenty-eight verses were identified, with a focus on diet and nutrition, personal hygiene, alcohol abstention, and the importance of a healthy lifestyle. These results suggest that the Quran could serve as an influential medium for culturally competent public health practitioners in diverse populations, particularly in Muslim communities, for improving and maintaining healthy behaviors.

  18. 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.

  19. Finding trends and statistical patterns in name mentions in news

    CERN Document Server

    Jayin, Abigail Mae C

    2015-01-01

    We extract the individual names of persons mentioned in news reports from a Philippine-based daily in the English language from 2010-2012. Names are extracted using a learning algorithm that filters adjacent capitalized words and runs it through a database of non-names grown through training. The number of mentions of individual names shows strong temporal fluctuations, indicative of the nature of "hot" trends and issues in society. Despite these strong variations, however, we observe stable rank-frequency distributions across different years in the form of power-laws with scaling exponents \\alpha = 0.7, reminiscent of the Zipf's law observed in lexical (i.e. non-name) words. Additionally, we observe that the adjusted frequency for each rank, or the frequency divided by the number of unique names having the same rank, shows a distribution with dual scaling behavior, with the higher-ranked names preserving the \\alpha exponent and the lower-ranked ones showing a power-law exponent \\alpha' = 2.9. We reproduced t...

  20. 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.)

  1. 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...

  2. 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.

  3. Automated recognition of malignancy mentions in biomedical literature

    Directory of Open Access Journals (Sweden)

    Liberman Mark Y

    2006-11-01

    Full Text Available Abstract Background The rapid proliferation of biomedical text makes it increasingly difficult for researchers to identify, synthesize, and utilize developed knowledge in their fields of interest. Automated information extraction procedures can assist in the acquisition and management of this knowledge. Previous efforts in biomedical text mining have focused primarily upon named entity recognition of well-defined molecular objects such as genes, but less work has been performed to identify disease-related objects and concepts. Furthermore, promise has been tempered by an inability to efficiently scale approaches in ways that minimize manual efforts and still perform with high accuracy. Here, we have applied a machine-learning approach previously successful for identifying molecular entities to a disease concept to determine if the underlying probabilistic model effectively generalizes to unrelated concepts with minimal manual intervention for model retraining. Results We developed a named entity recognizer (MTag, an entity tagger for recognizing clinical descriptions of malignancy presented in text. The application uses the machine-learning technique Conditional Random Fields with additional domain-specific features. MTag was tested with 1,010 training and 432 evaluation documents pertaining to cancer genomics. Overall, our experiments resulted in 0.85 precision, 0.83 recall, and 0.84 F-measure on the evaluation set. Compared with a baseline system using string matching of text with a neoplasm term list, MTag performed with a much higher recall rate (92.1% vs. 42.1% recall and demonstrated the ability to learn new patterns. Application of MTag to all MEDLINE abstracts yielded the identification of 580,002 unique and 9,153,340 overall mentions of malignancy. Significantly, addition of an extensive lexicon of malignancy mentions as a feature set for extraction had minimal impact in performance. Conclusion Together, these results suggest that the

  4. 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.

  5. 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.

  6. 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.

  7. 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.

  8. 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.

  9. 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.

  10. 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 (...

  11. 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.

  12. 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

  13. 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.

  14. 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.

  15. 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.

  16. 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.

  17. 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.

  18. 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

  19. 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.

  20. 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...

  1. 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.

  2. 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.

  3. 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.

  4. 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.

  5. 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.

  6. 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

  7. 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

  8. 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.

  9. 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.

  10. 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).

  11. 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.

  12. 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

  13. 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.

  14. 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...

  15. 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.

  16. 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.

  17. 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.

  18. 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.)

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

    Science.gov (United States)

    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.

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

    Directory of Open Access Journals (Sweden)

    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.

  1. 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.).

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

    Science.gov (United States)

    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

  3. 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

  4. 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.

  5. 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.

  6. 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

  7. 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

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

    Directory of Open Access Journals (Sweden)

    Elizabeth A Osterndorff-Kahanek

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

  9. 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.

  10. 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.

  11. 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.

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

    Science.gov (United States)

    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

  13. 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.

  14. 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.

  15. 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.

  16. 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

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

    Science.gov (United States)

    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.

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

    Directory of Open Access Journals (Sweden)

    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.

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

    Directory of Open Access Journals (Sweden)

    Manoj K. Sarma

    2014-01-01

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

  20. 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

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

    Science.gov (United States)

    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.

  2. 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.

  3. 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.

  4. 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...

  5. 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.

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

    Directory of Open Access Journals (Sweden)

    Timothy C. Durazzo

    2015-07-01

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

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

    Science.gov (United States)

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

    2016-02-23

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

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

    Energy Technology Data Exchange (ETDEWEB)

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

    2009-09-15

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

  9. 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.

  10. 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

  11. 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.

  12. 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.

  13. 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.

  14. 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

  15. 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.

  16. 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.

  17. 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.

  18. 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.

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

    Directory of Open Access Journals (Sweden)

    Benedito M.A.C.

    2001-01-01

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

  20. 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.

  1. 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.

  2. 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.

  3. 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.

  4. 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...

  5. 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…

  6. 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.

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

    Science.gov (United States)

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

    2012-01-01

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

  8. 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.

  9. 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

  10. 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...

  11. 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.

  12. 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.

  13. 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

  14. 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

  15. 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.

  16. 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.

  17. 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.

  18. 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.

  19. 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

  20. 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.

  1. 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

  2. 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.

  3. 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.

  4. 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.

  5. 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.

  6. 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.

  7. 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.

  8. 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...

  9. 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...

  10. 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.

  11. 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 ...

  12. 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.

  13. 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...

  14. 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.

  15. 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.

  16. 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.

  17. 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.

  18. 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.

  19. 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.

  20. 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.

  1. 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.

  2. 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.

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

    Science.gov (United States)

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

    2014-01-01

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

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

    Science.gov (United States)

    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.

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

    Science.gov (United States)

    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.

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

    Science.gov (United States)

    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.

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

    Science.gov (United States)

    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.

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

    Science.gov (United States)

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

    2017-08-01

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

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

    Science.gov (United States)

    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.

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

    Science.gov (United States)

    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.

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

    Science.gov (United States)

    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.

  12. 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.

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

    Directory of Open Access Journals (Sweden)

    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.

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

    Science.gov (United States)

    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.

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

    Science.gov (United States)

    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.

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

    Science.gov (United States)

    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.

  17. 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.

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

    Science.gov (United States)

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

    1996-01-01

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

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

    Science.gov (United States)

    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.

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

    Science.gov (United States)

    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.

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

    Science.gov (United States)

    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.

  2. 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.

  3. 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.

  4. 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

  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 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…

  7. 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.

  8. 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.

  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. 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.

  11. 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.

  12. 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).

  13. 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.

  14. 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

  15. 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.

  16. 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.

  17. 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.

  18. 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.

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

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    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

  20. 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.

  1. 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.

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

    Science.gov (United States)

    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.

  3. 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

  4. 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)

  5. 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...

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

    Science.gov (United States)

    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

  7. 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

  8. 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.

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

    Science.gov (United States)

    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

  10. 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

  11. 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.

  12. Arteriolosclerosis that affects multiple brain regions is linked to hippocampal sclerosis of ageing

    Science.gov (United States)

    Neltner, Janna H.; Abner, Erin L.; Baker, Steven; Schmitt, Frederick A.; Kryscio, Richard J.; Jicha, Gregory A.; Smith, Charles D.; Hammack, Eleanor; Kukull, Walter A.; Brenowitz, Willa D.; Van Eldik, Linda J.

    2014-01-01

    Hippocampal sclerosis of ageing is a prevalent brain disease that afflicts older persons and has been linked with cerebrovascular pathology. Arteriolosclerosis is a subtype of cerebrovascular pathology characterized by concentrically thickened arterioles. Here we report data from multiple large autopsy series (University of Kentucky Alzheimer’s Disease Centre, Nun Study, and National Alzheimer’s Coordinating Centre) showing a specific association between hippocampal sclerosis of ageing pathology and arteriolosclerosis. The present analyses incorporate 226 cases of autopsy-proven hippocampal sclerosis of ageing and 1792 controls. Case–control comparisons were performed including digital pathological assessments for detailed analyses of blood vessel morphology. We found no evidence of associations between hippocampal sclerosis of ageing pathology and lacunar infarcts, large infarcts, Circle of Willis atherosclerosis, or cerebral amyloid angiopathy. Individuals with hippocampal sclerosis of ageing pathology did not show increased rates of clinically documented hypertension, diabetes, or other cardiac risk factors. The correlation between arteriolosclerosis and hippocampal sclerosis of ageing pathology was strong in multiple brain regions outside of the hippocampus. For example, the presence of arteriolosclerosis in the frontal cortex (Brodmann area 9) was strongly associated with hippocampal sclerosis of ageing pathology (P ageing (n = 15) and control (n = 42) cases. Following technical studies to optimize immunostaining methods for small blood vessel visualization, our analyses focused on sections immunostained for smooth muscle actin (a marker of arterioles) and CD34 (an endothelial marker), with separate analyses on grey and white matter. A total of 43 834 smooth muscle actin-positive vascular profiles and 603 798 CD34-positive vascular profiles were evaluated. In frontal cortex of cases with hippocampal sclerosis of ageing, smooth muscle actin

  13. 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

  14. 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.

  15. 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.

  16. 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.

  17. 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

  18. 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

  19. 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

  20. 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.

  1. 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

  2. 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.

  3. 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.

  4. 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.

  5. 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.

  6. 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.

  7. 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.)

  8. 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.

  9. 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:

  10. 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.

  11. 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

  12. 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.

  13. 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).

  14. 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.

  15. Active Learning for Mention Detection: A Comparison of Sentence Selection Strategies

    CERN Document Server

    Madnani, Nitin; Kambhatla, Nanda; Roukos, Salim

    2009-01-01

    We propose and compare various sentence selection strategies for active learning for the task of detecting mentions of entities. The best strategy employs the sum of confidences of two statistical classifiers trained on different views of the data. Our experimental results show that, compared to the random selection strategy, this strategy reduces the amount of required labeled training data by over 50% while achieving the same performance. The effect is even more significant when only named mentions are considered: the system achieves the same performance by using only 42% of the training data required by the random selection strategy.

  16. 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.

  17. 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.

  18. 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.

  19. 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...

  20. The persuasive effects of personalization through : name mentioning in a smoking cessation message

    NARCIS (Netherlands)

    Dijkstra, Arie

    2014-01-01

    Mentioning the recipient's name in a persuasive message is one way to personalize messages in an attempt to increase persuasion. However, this type of personalization may lead to a self-threat that activates defensive reactions and to a subsequent decrease in persuasion. A self-affirmation procedure

  1. Collectors of botanical specimens from the flora area mentioned in the Flora of Ethiopia and Eritrea

    DEFF Research Database (Denmark)

    Friis, Ib

    2009-01-01

    Information based on all available sources about full name, nationality, profession, area and period of collection, with whom they are known to have made joint collections, herbaria in which the collections have been deposited etc., for all collectors mentioned in vol. 1-7 of the Flora of Ethiopia...

  2. 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 ...

  3. 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.

  4. 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.

  5. 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.

  6. 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.

  7. 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.

  8. 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.

  9. 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.)

  10. 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.

  11. 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.

  12. 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

  13. 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

  14. 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.

  15. 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.

  16. 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.

  17. 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.)

  18. 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.

  19. 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

  20. 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

  1. 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.

  2. 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.

  3. 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.

  4. 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.

  5. Trend in rates for deaths with mention of schizophrenia on death certificates of US residents, 1999-2010.

    Science.gov (United States)

    Polednak, Anthony P

    2014-07-01

    Trends in mortality rates for schizophrenia using multiple causes of death (including contributory causes) coded on death certificates in the US resident population apparently have not been reported. Age-standardized rates for deaths per 100,000 in 1999-2010 at age 15+ years (and for 15-64 and 65+ years) with mention of schizophrenia were examined for the US resident population, including variation by age, gender, race (blacks/African Americans and whites) and region. Deaths at age 15+ years coded with schizophrenia as underlying cause were only 12 % of all deaths with mention of schizophrenia, for which the rate declined from 1.58 in 1999 (3,407 deaths) to 1.32 in 2010 (3,422 deaths) (percentage change or PC = -16 %). Declines were larger in females than males, in whites than blacks, and occurred in the Northeast, Midwest and South but not the West. The rate increased for age 15-64 years (PC = +28 %) (mainly in males), however, while declining for age 65+ years (PC = -35 %). For deaths at age 15-64 years with schizophrenia coded as other than the underlying cause, the largest continuous increase was for endocrine-metabolic diseases (predominantly diabetes mellitus) as underlying cause, with smaller increases in males for cardiovascular diseases, external causes and neoplasms. Trends in the US rate for deaths with mention of schizophrenia varied among the sociodemographic groups examined. The lack of decline for age 15-64 years requires further study especially with regard to mediators (e.g., obesity) of excess mortality in schizophrenia identified from cohort studies.

  6. Cerebral perfusion imaging with bolus harmonic imaging (Honorable Mention Poster Award)

    Science.gov (United States)

    Kier, Christian; Toth, Daniel; Meyer-Wiethe, Karsten; Schindler, Angela; Cangur, Hakan; Seidel, Gunter; Aach, Til

    2005-04-01

    Fast visualisation of cerebral microcirculation supports diagnosis of acute stroke. However, the commonly used CT/MRI-based methods are time consuming, costly and not applicable to every patient. The bolus perfusion harmonic imaging (BHI) method is an ultrasound imaging technique which makes use of the fact, that ultrasound contrast agents unlike biological tissues resonate at harmonic frequencies. Exploiting this effect, the contrast between perfused and non-perfused areas can be improved. Thus, BHI overcomes the low signal-to-noise ratio of transcranial ultrasound and the high impedance of the skull. By analysing image sequences, visualising the qualitative characteristics of an US contrast agent bolus injection becomes possible. The analysis consists of calculating four perfusion-related parameters, Local Peak Intensity, Time To Peak, Area Under Curve, and Average Rising, from the time/intensity curve and providing them as colour-coded images. For calculating these parameters the fundamental assumption is that image intensity corresponds to contrast agent concentration which in turn shows the perfusion of the corresponding brain region. In a clinical study on patients suffering from acute ischemic stroke it is shown that some of the parameters correlate significantly to the infarction area. Thus, BHI becomes a less time-consuming and inexpensive bedside method for diagnosis of cerebral perfusion deficits.

  7. 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.

  8. 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.

  9. 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.

  10. 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

  11. 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

  12. 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.

  13. A text mining approach to detect mentions of protein glycosylation in biomedical text.

    Science.gov (United States)

    Shukla, Daksha; Jayaraman, Valadi K

    2012-01-01

    Protein Glycosylation is an important post translational event that plays a pivotal role in protein folding and protein is trafficking. We describe a dictionary based and a rule based approach to mine 'mentions' of protein glycosylation in text. The dictionary based approach relies on a set of manually curated dictionaries specially constructed to address this task. Abstracts are then screened for the 'mentions' of words from these dictionaries which are further scored followed by classification on the basis of a threshold. The rule based approaches also relies on the words in the dictionary to arrive at the features which are used for classification. The performance of the system using both the approaches has been evaluated using a manually curated corpus of 3133 abstracts. The evaluation suggests that the performance of the Rule based approach supersedes that of the Dictionary based approach.

  14. 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

  15. Text and Structural Data Mining of Influenza Mentions in Web and Social Media

    OpenAIRE

    Karan P Singh; Mikler, Armin R.; Cook, Diane J.; Courtney D. Corley

    2010-01-01

    Text and structural data mining of web and social media (WSM) provides a novel disease surveillance resource and can identify online communities for targeted public health communications (PHC) to assure wide dissemination of pertinent information. WSM that mention influenza are harvested over a 24-week period, 5 October 2008 to 21 March 2009. Link analysis reveals communities for targeted PHC. Text mining is shown to identify trends in flu posts that correlate to real-world influenza-like ill...

  16. 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.

  17. 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.

  18. 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.

  19. 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

  20. 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.

  1. 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.

  2. 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

  3. 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.

  4. 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

  5. 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.

  6. Mention Detection for Coreference Resolution in Polish. Development of the Formal Grammar

    Directory of Open Access Journals (Sweden)

    Alicja Wójcicka

    2016-12-01

    Full Text Available Mention Detection for Coreference Resolution in Polish. Development of the Formal Grammar This paper presents the results of an improvement and extension of the Shallow Grammar of Polish, designed for the needs of the Computer-based Methods for Coreference Resolution in Polish Texts (CORE project. The role of the Grammar was to detect nominal groups (i.e. multi-level nested phrases that could be considered as mentions in coreference resolution tasks. In this article, the reorganization and changes to the Grammar are described, as well as the results of an evaluation of the Polish Coreference Corpus with manual annotations of mentions and coreferential expressions. A comparison of the second version of the Grammar with an evaluation of the first version reveals an improvement to the recall and F1 measures.   Parsing płytki relacji koreferencji w języku polskim. Rozwój gramatyki formalnej Celem artykułu jest przedstawienie rezultatów prac zmierzających do rozszerzenia gramatyki powierzchniowej języka polskiego, stworzonej na potrzeby projektu "Komputerowe metody identyfikacji nawiązań w tekstach polskich" (grant NCN nr 6505/B/T02/2011/40, oraz poprawy wyników jej działania. Rolą gramatyki powierzchniowej jest wykrywanie grup nominalnych, które mogą wchodzić w relację koreferencji z innymi wyrażeniami w tekście. Nowa gramatyka została przetestowana z użyciem Polskiego Korpusu Koreferencyjnego, w którym grupy nominalne oraz relacje koreferencji między nimi zostały oznaczone ręcznie. Porównanie nowej wersji gramatyki z wersją poprzednią wykazało poprawę zarówno skuteczności wykrywania odpowiednich grup, jak i wzrost miary F1.

  7. 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.

  8. 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.

  9. 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.

  10. 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.

  11. 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.

  12. 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

  13. 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.

  14. 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.

  15. 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.

  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. 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.

  18. Time and Causation in Discourse: Temporal Proximity, Implicit Causality, and Re-mention Biases.

    Science.gov (United States)

    Dery, Jeruen E; Bittner, Dagmar

    2016-08-01

    Using referential processing in discourse featuring implicit causality verbs as a test case, we demonstrate how a discourse's causal and temporal dimensions interact. We show that referential processing is affected by multiple discourse biases, and that these biases do not have uniform effects. In three discourse continuation experiments, we show that the bias to re-mention a particular referent in discourse involving implicit causality verbs is not only affected by the verb's implicit causality bias, but also by the discourse's temporal structure, which at times, can even override the implicit causality bias. Our results add to the growing number of studies that show how various discourse dimensions interact in discourse processing.

  19. Text and structural data mining of influenza mentions in Web and social media.

    Science.gov (United States)

    Corley, Courtney D; Cook, Diane J; Mikler, Armin R; Singh, Karan P

    2010-02-01

    Text and structural data mining of web and social media (WSM) provides a novel disease surveillance resource and can identify online communities for targeted public health communications (PHC) to assure wide dissemination of pertinent information. WSM that mention influenza are harvested over a 24-week period, 5 October 2008 to 21 March 2009. Link analysis reveals communities for targeted PHC. Text mining is shown to identify trends in flu posts that correlate to real-world influenza-like illness patient report data. We also bring to bear a graph-based data mining technique to detect anomalies among flu blogs connected by publisher type, links, and user-tags.

  20. Text and Structural Data Mining of Influenza Mentions in Web and Social Media

    Directory of Open Access Journals (Sweden)

    Karan P. Singh

    2010-02-01

    Full Text Available Text and structural data mining of web and social media (WSM provides a novel disease surveillance resource and can identify online communities for targeted public health communications (PHC to assure wide dissemination of pertinent information. WSM that mention influenza are harvested over a 24-week period, 5 October 2008 to 21 March 2009. Link analysis reveals communities for targeted PHC. Text mining is shown to identify trends in flu posts that correlate to real-world influenza-like illness patient report data. We also bring to bear a graph-based data mining technique to detect anomalies among flu blogs connected by publisher type, links, and user-tags.

  1. 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

  2. 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.

  3. 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

  4. 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.

  5. 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.

  6. 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.

  7. 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.

  8. 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...

  9. 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.

  10. 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.

  11. 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

  12. Relevance of the Mention of Antioxidant Properties in Yogurt Labels: In Vitro Evaluation and Chromatographic Analysis

    Directory of Open Access Journals (Sweden)

    Eliana Pereira

    2013-06-01

    Full Text Available The purpose of the inclusion of fruit (natural additives in yogurt aims to increase its antioxidant activity and functionality. Herein, a comparative study of the antioxidant potential of yogurts with pieces of various fruits was performed, including yogurts with mention of antioxidant properties in the label. Free radicals scavenging activity, reducing power and inhibition of lipid peroxidation were evaluated by in vitro assays, as were the contents in antioxidants such as phenolics, flavonoids, sugars and tocopherols. After analyzing thirteen yogurts containing fruit pieces and a natural one (control, the most interesting were yogurts with pieces of berries (for phenolics, flavonoids and 2,2-dipheny-1-picrylhydrazyl (DPPH scavenging activity, pineapple (for reducing power, blackberry (for β-carotene bleaching inhibition, blackberry “antioxidant” (for tocopherols and cherry (for sugars. The mention of “antioxidant” in the label was relevant for tocopherols, sugars, DPPH scavenging activity and reducing power. No synergisms were observed in yogurts prepared with pieces of different fruits. Nevertheless, the addition of fruit pieces to yogurt was favorable for antioxidant content, increasing the protection of the consumer against diseases related to oxidative stress.

  13. Relevance of the Mention of Antioxidant Properties in Yogurt Labels: In Vitro Evaluation and Chromatographic Analysis.

    Science.gov (United States)

    Pereira, Eliana; Barros, Lillian; Ferreira, Isabel C F R

    2013-01-01

    The purpose of the inclusion of fruit (natural additives) in yogurt aims to increase its antioxidant activity and functionality. Herein, a comparative study of the antioxidant potential of yogurts with pieces of various fruits was performed, including yogurts with mention of antioxidant properties in the label. Free radicals scavenging activity, reducing power and inhibition of lipid peroxidation were evaluated by in vitro assays, as were the contents in antioxidants such as phenolics, flavonoids, sugars and tocopherols. After analyzing thirteen yogurts containing fruit pieces and a natural one (control), the most interesting were yogurts with pieces of berries (for phenolics, flavonoids and 2,2-dipheny-1-picrylhydrazyl (DPPH) scavenging activity), pineapple (for reducing power), blackberry (for β-carotene bleaching inhibition), blackberry "antioxidant" (for tocopherols) and cherry (for sugars). The mention of "antioxidant" in the label was relevant for tocopherols, sugars, DPPH scavenging activity and reducing power. No synergisms were observed in yogurts prepared with pieces of different fruits. Nevertheless, the addition of fruit pieces to yogurt was favorable for antioxidant content, increasing the protection of the consumer against diseases related to oxidative stress.

  14. 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.

  15. 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

  16. 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...

  17. 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.

  18. 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.

  19. 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.

  20. 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.

  1. 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.)

  2. 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.

  3. 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.

  4. 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.

  5. 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.

  6. Sustained spatial attention to vibrotactile stimulation in the flutter range: relevant brain regions and their interaction.

    Directory of Open Access Journals (Sweden)

    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

  7. 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, we used the electrical kindling model of epilepsy to determine whether seizures that originate in different brain regions have differential effects on hippocampal interneuron subpopulations. Long-Evans rats received 99 electrical stimulations of the hippocampus, amygdala, or caudate nucleus, followed by sacrifice and immunohistochemical or western blot analyses. We analyzed markers of dendritic (somatostatin), perisomatic (parvalbumin), and interneuron-selective (calretinin) inhibition, as well as an overall indicator (GAD67) of interneuron distribution across all major hippocampal subfields. Our results indicate that kindling produces selective effects on the number and morphology of different functional classes of GABAergic interneurons. In particular, limbic kindling appears to enhance dendritic inhibition, indicated by a greater number of somatostatin-immunoreactive (-ir) cells in the CA1 pyramidal layer and robust morphological sprouting in the dentate gyrus. We also found a reduction in the number of interneuron-selective calretinin-ir cells in the dentate gyrus of hippocampal-kindled rats, which suggests a possible reduction of synchronized dendritic inhibition. In contrast, perisomatic inhibition indicated by parvalbumin immunoreactivity appears to be largely resilient to the effects of kindling. Finally, we found a significant induction in the number of GAD67-cells in caudate-kindled rats in the dentate gyrus and CA3 hippocampal subfields. Taken together, our results demonstrate that kindling has subfield-selective effects on the different functional classes of hippocampal GABAergic interneurons. J. Comp. Neurol. 525:389-406, 2017. © 2016 Wiley Periodicals, Inc. © 2016 Wiley Periodicals, Inc.

  8. Brain regions involved in processing facial identity and expression are differentially selective for surface and edge information.

    Science.gov (United States)

    Harris, Richard J; Young, Andrew W; Andrews, Timothy J

    2014-08-15

    Although different brain regions are widely considered to be involved in the recognition of facial identity and expression, it remains unclear how these regions process different properties of the visual image. Here, we ask how surface-based reflectance information and edge-based shape cues contribute to the perception and neural representation of facial identity and expression. Contrast-reversal was used to generate images in which normal contrast relationships across the surface of the image were disrupted, but edge information was preserved. In a behavioural experiment, contrast-reversal significantly attenuated judgements of facial identity, but only had a marginal effect on judgements of expression. An fMR-adaptation paradigm was then used to ask how brain regions involved in the processing of identity and expression responded to blocks comprising all normal, all contrast-reversed, or a mixture of normal and contrast-reversed faces. Adaptation in the posterior superior temporal sulcus--a region directly linked with processing facial expression--was relatively unaffected by mixing normal with contrast-reversed faces. In contrast, the response of the fusiform face area--a region linked with processing facial identity--was significantly affected by contrast-reversal. These results offer a new perspective on the reasons underlying the neural segregation of facial identity and expression in which brain regions involved in processing invariant aspects of faces, such as identity, are very sensitive to surface-based cues, whereas regions involved in processing changes in faces, such as expression, are relatively dependent on edge-based cues.

  9. Rethink Chinese Culture Mentioned by Foreigners and Find a Way to Make It Heard

    Institute of Scientific and Technical Information of China (English)

    ZHANG Yu

    2015-01-01

    As China is getting more and more attention and Chinese culture is marching to the world, there come many internet videos on how foreigners think about China. By analyzing two videos“Chinese in foreigners’eyes”and“China, How is it”, I am going to talk about the most impressive culture mentioned by foreigners in these videos with further discussion. And only when we deeply understand our culture, not just see it by its out layer, can we explain our culture to the world effectively. In the first part, I will talk about the most impressive Chinese culture in foreigners’eyes, and in the second part I will talk about some effective and objective ways to show what China is about.

  10. SkipCor: skip-mention coreference resolution using linear-chain conditional random fields.

    Directory of Open Access Journals (Sweden)

    Slavko Žitnik

    Full Text Available Coreference resolution tries to identify all expressions (called mentions in observed text that refer to the same entity. Beside entity extraction and relation extraction, it represents one of the three complementary tasks in Information Extraction. In this paper we describe a novel coreference resolution system SkipCor that reformulates the problem as a sequence labeling task. None of the existing supervised, unsupervised, pairwise or sequence-based models are similar to our approach, which only uses linear-chain conditional random fields and supports high scalability with fast model training and inference, and a straightforward parallelization. We evaluate the proposed system against the ACE 2004, CoNLL 2012 and SemEval 2010 benchmark datasets. SkipCor clearly outperforms two baseline systems that detect coreferentiality using the same features as SkipCor. The obtained results are at least comparable to the current state-of-the-art in coreference resolution.

  11. MutationFinder: a high-performance system for extracting point mutation mentions from text.

    Science.gov (United States)

    Caporaso, J Gregory; Baumgartner, William A; Randolph, David A; Cohen, K Bretonnel; Hunter, Lawrence

    2007-07-15

    Discussion of point mutations is ubiquitous in biomedical literature, and manually compiling databases or literature on mutations in specific genes or proteins is tedious. We present an open-source, rule-based system, MutationFinder, for extracting point mutation mentions from text. On blind test data, it achieves nearly perfect precision and a markedly improved recall over a baseline. MutationFinder, along with a high-quality gold standard data set, and a scoring script for mutation extraction systems have been made publicly available. Implementations, source code and unit tests are available in Python, Perl and Java. MutationFinder can be used as a stand-alone script, or imported by other applications. http://bionlp.sourceforge.net.

  12. Regionally distinct responses of microglia and glial progenitor cells to whole brain irradiation in adult and aging rats.

    Science.gov (United States)

    Hua, Kun; Schindler, Matthew K; McQuail, Joseph A; Forbes, M Elizabeth; Riddle, David R

    2012-01-01

    Radiation therapy has proven efficacy for treating brain tumors and metastases. Higher doses and larger treatment fields increase the probability of eliminating neoplasms and preventing reoccurrence, but dose and field are limited by damage to normal tissues. Normal tissue injury is greatest during development and in populations of proliferating cells but also occurs in adults and older individuals and in non-proliferative cell populations. To better understand radiation-induced normal tissue injury and how it may be affected by aging, we exposed young adult, middle-aged, and old rats to 10 Gy of whole brain irradiation and assessed in gray- and white matter the responses of microglia, the primary cellular mediators of radiation-induced neuroinflammation, and oligodendrocyte precursor cells, the largest population of proliferating cells in the adult brain. We found that aging and/or irradiation caused only a few microglia to transition to the classically "activated" phenotype, e.g., enlarged cell body, few processes, and markers of phagocytosis, that is seen following more damaging neural insults. Microglial changes in response to aging and irradiation were relatively modest and three markers of reactivity - morphology, proliferation, and expression of the lysosomal marker CD68- were regulated largely independently within individual cells. Proliferation of oligodendrocyte precursors did not appear to be altered during normal aging but increased following irradiation. The impacts of irradiation and aging on both microglia and oligodendrocyte precursors were heterogeneous between white- and gray matter and among regions of gray matter, indicating that there are regional regulators of the neural response to brain irradiation. By several measures, the CA3 region of the hippocampus appeared to be differentially sensitive to effects of aging and irradiation. The changes assessed here likely contribute to injury following inflammatory challenges like brain irradiation and

  13. Regionally distinct responses of microglia and glial progenitor cells to whole brain irradiation in adult and aging rats.

    Directory of Open Access Journals (Sweden)

    Kun Hua

    Full Text Available Radiation therapy has proven efficacy for treating brain tumors and metastases. Higher doses and larger treatment fields increase the probability of eliminating neoplasms and preventing reoccurrence, but dose and field are limited by damage to normal tissues. Normal tissue injury is greatest during development and in populations of proliferating cells but also occurs in adults and older individuals and in non-proliferative cell populations. To better understand radiation-induced normal tissue injury and how it may be affected by aging, we exposed young adult, middle-aged, and old rats to 10 Gy of whole brain irradiation and assessed in gray- and white matter the responses of microglia, the primary cellular mediators of radiation-induced neuroinflammation, and oligodendrocyte precursor cells, the largest population of proliferating cells in the adult brain. We found that aging and/or irradiation caused only a few microglia to transition to the classically "activated" phenotype, e.g., enlarged cell body, few processes, and markers of phagocytosis, that is seen following more damaging neural insults. Microglial changes in response to aging and irradiation were relatively modest and three markers of reactivity - morphology, proliferation, and expression of the lysosomal marker CD68- were regulated largely independently within individual cells. Proliferation of oligodendrocyte precursors did not appear to be altered during normal aging but increased following irradiation. The impacts of irradiation and aging on both microglia and oligodendrocyte precursors were heterogeneous between white- and gray matter and among regions of gray matter, indicating that there are regional regulators of the neural response to brain irradiation. By several measures, the CA3 region of the hippocampus appeared to be differentially sensitive to effects of aging and irradiation. The changes assessed here likely contribute to injury following inflammatory challenges like

  14. Specific binding of /sup 125/I-salmon calcitonin to rat brain. Regional variation and calcitonin specificity

    Energy Technology Data Exchange (ETDEWEB)

    Nakamuta, H.; Furukawa, S.; Koida, M. (Nagasaki Univ. (Japan). Faculty of Pharmaceutical Sciences); Yajima, H.; Orlowski, R.C.

    1981-02-01

    Rat brain particulate fraction was found to contain binding sites for /sup 125/I-Salmon Calcitonin-I (/sup 125/I-SCT). Maximum binding occurred in the physiological pH range of 7.25 - 7.5. The binding reaction proceeded in a temperature-dependent manner. Binding sites were broadly distributed among the various rat brain regions and considerable regional differences existed in the affinity and density as detected by Scatchard analysis. The highest affinity was recorded in the case of the hypothalamus and the lowest in the case of the cerebellum. The KD (nM) and Bmax (pmole/mg protein) estimated for the binding to four regions were as follows: hypothalamus: 1.4 and 0.19, midbrain, hippocampus plus striatum: 1.5 and 0.08, pon plus medulla oblongata: 3.0 and 0.15 and cerebellum: 8.3 and 0.20. Using a particulate fraction of rat brain void of cerebellum and cortices, a binding assay for calcitonins was developed. Binding of /sup 125/I-SCT was inhibited by unlabeled salmon, (Asu sup(1,7))-eel and porcine calcitonins in a dose-dependent manner and the IC50s were 2.0, 8.0 and 30 nM, respectively. The IC50s were comparable to those estimated using a kidney particulate fraction. Human calcitonin, ..beta..-endorphin and substance P were weak inhibitors of the binding. Other peptides, drugs and putative neurotransmitters tested (totally 23 substances) failed to inhibit the binding at concentrations of 1.0 ..mu..M. The physiological significance of brain binding sites for calcitonin, with the possibility that the brain may possess endogenous ligands for these sites are discussed.

  15. Simultaneous recording of fluorescence and electrical signals by photometric patch electrode in deep brain regions in vivo

    Science.gov (United States)

    Hirai, Yasuharu; Nishino, Eri

    2015-01-01

    Despite its widespread use, high-resolution imaging with multiphoton microscopy to record neuronal signals in vivo is limited to the surface of brain tissue because of limited light penetration. Moreover, most imaging studies do not simultaneously record electrical neural activity, which is, however, crucial to understanding brain function. Accordingly, we developed a photometric patch electrode (PME) to overcome the depth limitation of optical measurements and also enable the simultaneous recording of neural electrical responses in deep brain regions. The PME recoding system uses a patch electrode to excite a fluorescent dye and to measure the fluorescence signal as a light guide, to record electrical signal, and to apply chemicals to the recorded cells locally. The optical signal was analyzed by either a spectrometer of high light sensitivity or a photomultiplier tube depending on the kinetics of the responses. We used the PME in Oregon Green BAPTA-1 AM-loaded avian auditory nuclei in vivo to monitor calcium signals and electrical responses. We demonstrated distinct response patterns in three different nuclei of the ascending auditory pathway. On acoustic stimulation, a robust calcium fluorescence response occurred in auditory cortex (field L) neurons that outlasted the electrical response. In the auditory midbrain (inferior colliculus), both responses were transient. In the brain-stem cochlear nucleus magnocellularis, calcium response seemed to be effectively suppressed by the activity of metabotropic glutamate receptors. In conclusion, the PME provides a powerful tool to study brain function in vivo at a tissue depth inaccessible to conventional imaging devices. PMID:25761950

  16. Microtask crowdsourcing for disease mention annotation in PubMed abstracts.

    Science.gov (United States)

    Good, Benjamin M; Nanis, Max; Wu, Chunlei; Su, Andrew I

    2015-01-01

    Identifying concepts and relationships in biomedical text enables knowledge to be applied in computational analyses. Many biological natural language processing (BioNLP) projects attempt to address this challenge, but the state of the art still leaves much room for improvement. Progress in BioNLP research depends on large, annotated corpora for evaluating information extraction systems and training machine learning models. Traditionally, such corpora are created by small numbers of expert annotators often working over extended periods of time. Recent studies have shown that workers on microtask crowdsourcing platforms such as Amazon's Mechanical Turk (AMT) can, in aggregate, generate high-quality annotations of biomedical text. Here, we investigated the use of the AMT in capturing disease mentions in PubMed abstracts. We used the NCBI Disease corpus as a gold standard for refining and benchmarking our crowdsourcing protocol. After several iterations, we arrived at a protocol that reproduced the annotations of the 593 documents in the 'training set' of this gold standard with an overall F measure of 0.872 (precision 0.862, recall 0.883). The output can also be tuned to optimize for precision (max = 0.984 when recall = 0.269) or recall (max = 0.980 when precision = 0.436). Each document was completed by 15 workers, and their annotations were merged based on a simple voting method. In total 145 workers combined to complete all 593 documents in the span of 9 days at a cost of $.066 per abstract per worker. The quality of the annotations, as judged with the F measure, increases with the number of workers assigned to each task; however minimal performance gains were observed beyond 8 workers per task. These results add further evidence that microtask crowdsourcing can be a valuable tool for generating well-annotated corpora in BioNLP. Data produced for this analysis are available at http://figshare.com/articles/Disease_Mention_Annotation_with_Mechanical_Turk/1126402.

  17. Amplitude of Sensorimotor Mu Rhythm Is Correlated with BOLD from Multiple Brain Regions: A Simultaneous EEG-fMRI Study

    Science.gov (United States)

    Yin, Siyang; Liu, Yuelu; Ding, Mingzhou

    2016-01-01

    The mu rhythm is a field oscillation in the ∼10Hz range over the sensorimotor cortex. For decades, the suppression of mu (event-related desynchronization) has been used to index movement planning, execution, and imagery. Recent work reports that non-motor processes, such as spatial attention and movement observation, also desynchronize mu, raising the possibility that the mu rhythm is associated with the activity of multiple brain regions and systems. In this study, we tested this hypothesis by recording simultaneous resting-state EEG-fMRI from healthy subjects. Independent component analysis (ICA) was applied to extract the mu components. The amplitude (power) fluctuations of mu were estimated as a time series using a moving-window approach, which, after convolving with a canonical hemodynamic response function (HRF), was correlated with blood-oxygen-level-dependent (BOLD) signals from the entire brain. Two main results were found. First, mu power was negatively correlated with BOLD from areas of the sensorimotor network, the attention control network, the putative mirror neuron system, and the network thought to support theory of mind. Second, mu power was positively correlated with BOLD from areas of the salience network, including anterior cingulate cortex and anterior insula. These results are consistent with the hypothesis that sensorimotor mu rhythm is associated with multiple brain regions and systems. They also suggest that caution should be exercised when attempting to interpret mu modulation in terms of a single brain network. PMID:27499736

  18. Parcellation of the healthy neonatal brain into 107 regions using atlas propagation through intermediate time points in childhood

    Directory of Open Access Journals (Sweden)

    Manuel eBlesa Cabez

    2016-05-01

    Full Text Available Neuroimage analysis pipelines rely on parcellated atlases generated from healthy individuals to provide anatomic context to structural and diffusion MRI data. Atlases constructed using adult data introduce bias into studies of early brain development. We aimed to create a neonatal brain atlas of healthy subjects that can be applied to multi-modal MRI data. Structural and diffusion 3T MRI scans were acquired soon after birth from 33 typically developing neonates born at term (mean postmenstrual age at birth 39+5 weeks, range 37+2-41+6. An adult brain atlas (SRI24/TZO was propagated to the neonatal data using temporal registration via childhood templates with dense temporal samples (NIH Pediatric Database, with the final atlas (Edinburgh Neonatal Atlas, ENA33 constructed using the Symmetric Group Normalization method. After this step, the computed final transformations were applied to T2-weighted data, and fractional anisotropy, mean diffusivity, and tissue segmentations to provide a multi-modal atlas with 107 anatomical regions; a symmetric version was also created to facilitate studies of laterality. Volumes of each region of interest were measured to provide reference data from normal subjects. Because this atlas is generated from step-wise propagation of adult labels through intermediate time points in childhood, it may serve as a useful starting point for modelling brain growth during development.

  19. 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

  20. The acute phase response and soman-induced status epilepticus: temporal, regional and cellular changes in rat brain cytokine concentrations

    Directory of Open Access Journals (Sweden)

    Kan Robert K

    2010-07-01

    Full Text Available Abstract Background Neuroinflammation occurs following brain injury, including soman (GD induced status epilepticus (SE, and may contribute to loss of neural tissue and declined behavioral function. However, little is known about this important pathological process following GD exposure. Limited transcriptional information on a small number of brain-expressed inflammatory mediators has been shown following GD-induced SE and even less information on protein upregulation has been elucidated. The purpose of this study is to further characterize the regional and temporal progression of the neuroinflammatory process following acute GD-induced SE. Methods The protein levels of 10 cytokines was quantified using bead multiplex immunoassays in damaged brain regions (i.e., piriform cortex, hippocampus and thalamus up to 72 hours following seizure onset. Those factors showing significant changes were then localized to neural cells using fluorescent IHC. Results A significant concentration increase was observed in all injured brain regions for four acute phase response (APR induction cytokines: interleukin (IL-1α, IL-1β, IL-6, and tumor necrosis factor (TNF-α. Increases in these APR cytokines corresponded both temporally and regionally to areas of known seizure damage and neuronal death. Neurotoxic cytokines IL-1α and IL-1β were primarily expressed by activated microglia whereas the potentially neuroprotective cytokine IL-6 was expressed by neurons and hypertrophic astrocytes. Conclusions Increases in neurotoxic cytokines likely play an active role in the progression of GD-induced SE neuropathology though the exact role that these and other cytokines play in this process require further study.

  1. Differential Expression of FosB Proteins and Potential Target Genes in Select Brain Regions of Addiction and Depression Patients

    OpenAIRE

    Gajewski, Paula A.; Turecki, Gustavo; Robison, Alfred J.

    2016-01-01

    Chronic exposure to stress or drugs of abuse has been linked to altered gene expression throughout the body, and changes in gene expression in discrete brain regions are thought to underlie many psychiatric diseases, including major depressive disorder and drug addiction. Preclinical models of these disorders have provided evidence for mechanisms of this altered gene expression, including transcription factors, but evidence supporting a role for these factors in human patients has been slow t...

  2. Magnetic resonance imaging of regional hemodynamic and cerebrovascular recovery after lateral fluid-percussion brain injury in rats

    OpenAIRE

    2010-01-01

    Hemodynamic and cerebrovascular factors are crucially involved in secondary damage after traumatic brain injury (TBI). With magnetic resonance imaging, this study aimed to quantify regional cerebral blood flow (CBF) by arterial spin labeling and cerebral blood volume by using an intravascular contrast agent, during 14 days after lateral fluid-percussion injury (LFPI) in rats. Immunohistochemical analysis of vessel density was used to evaluate the contribution of vascular damage. Results show ...

  3. [Preliminary evidence of neurobiological and behavioral consequences of exposure to childhood maltreatment on regional brain development].

    Science.gov (United States)

    Tomoda, Akemi

    2011-09-01

    In recent years, the topic of child abuse as an issue facing Japanese society has gained considerable attention with regard to the field of medicine and education and also in scenarios that relate to child care. The definition of child abuse includes abusing children verbally or psychologically, and is not limited to abusing children physically such as beating, sexual abuse, or neglect. Recent studies have revealed that emotional trauma during childhood development could be much more difficult to treat than physical abuse. Severe abuse during childhood can cause abnormal brain development and have a negative impact later in life. In this review, I will introduce the mechanisms of brain damage due to child abuse with consideration of how and when child abuse can have an impact on the victims' brains. The information presented is based on a collaborative study with the Psychiatry Department at Harvard University on the relationship between brain functions and the human mind.

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

    Directory of Open Access Journals (Sweden)

    Wang Kate

    2010-05-01

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

  5. Validating computationally predicted TMS stimulation areas using direct electrical stimulation in patients with brain tumors near precentral regions

    Directory of Open Access Journals (Sweden)

    Alexander Opitz

    2014-01-01

    Full Text Available The spatial extent of transcranial magnetic stimulation (TMS is of paramount interest for all studies employing this method. It is generally assumed that the induced electric field is the crucial parameter to determine which cortical regions are excited. While it is difficult to directly measure the electric field, one usually relies on computational models to estimate the electric field distribution. Direct electrical stimulation (DES is a local brain stimulation method generally considered the gold standard to map structure–function relationships in the brain. Its application is typically limited to patients undergoing brain surgery. In this study we compare the computationally predicted stimulation area in TMS with the DES area in six patients with tumors near precentral regions. We combine a motor evoked potential (MEP mapping experiment for both TMS and DES with realistic individual finite element method (FEM simulations of the electric field distribution during TMS and DES. On average, stimulation areas in TMS and DES show an overlap of up to 80%, thus validating our computational physiology approach to estimate TMS excitation volumes. Our results can help in understanding the spatial spread of TMS effects and in optimizing stimulation protocols to more specifically target certain cortical regions based on computational modeling.

  6. Region-selective effects of neuroinflammation and antioxidant treatment on peripheral benzodiazepine receptors and NMDA receptors in the rat brain

    Energy Technology Data Exchange (ETDEWEB)

    Biegon, A.; Alvarado, M.; Budinger, T.F.; Grossman, R.; Hensley, K.; West, M.S.; Kotake, Y.; Ono, M.; Floyd, R.A.

    2001-12-10

    Following induction of acute neuroinflammation by intracisternal injection of endotoxin (lipopolysaccharide) in rats, quantitative autoradiography was used to assess the regional level of microglial activation and glutamate (NMDA) receptor binding. The possible protective action of the antioxidant phenyl-tert-butyl nitrone in this model was tested by administering the drug in the drinking water for 6 days starting 24 hours after endotoxin injection. Animals were killed 7 days post-injection and consecutive cryostat brain sections labeled with [3H]PK11195 as a marker of activated microglia and [125I]iodoMK801 as a marker of the open-channel, activated state of NMDA receptors. Lipopolysaccharide increased [3H]PK11195 binding in the brain, with the largest increases (2-3 fold) in temporal and entorhinal cortex, hippocampus, and substantia innominata. A significant (>50 percent) decrease in [125I]iodoMK801 binding was found in the same brain regions. Phenyl-tert-butyl nitrone treatment resulted in a partial inhibition ({approx}25 percent decrease) of the lipopolysaccharide-induced increase in [3H]PK11195 binding but completely reversed the lipopolysaccharide-induced decrease in [125I]iodoMK80 binding in the entorhinal cortex, hippocampus, and substantia innominata. Loss of NMDA receptor function in cortical and hippocampal regions may contribute to the cognitive deficits observed in diseases with a neuroinflammatory component, such as meningitis or Alzheimer's disease.

  7. Epigenetics in schizophrenia: a pilot study of global DNA methylation in different brain regions associated with higher cognitive functions.

    Directory of Open Access Journals (Sweden)

    Raúl Alelú-Paz

    2016-09-01

    Full Text Available Attempts to discover genes that are involved in the pathogenesis of major psychiatric disorders have been frustrating and often fruitless. Concern is building about the need to understand the complex ways in which nature and nurture interact to produce mental illness. We analyze the epigenome in several brain regions from schizophrenic patients with severe cognitive impairment using high-resolution (450k DNA methylation array. We identified 159 differentially methylated CpG sites included in known and novel candidate genes sequences as well as in and intergenic sequences wich functions remain unknown. We found that altered DNA methylation is not restricted to a particular region, but includes others such as CpG shelves and gene bodies, indicating the presence of different DNA methylation signatures depending on the brain area analyzed. Our findings suggest that epimutations are not relatables between different tissues or even between tissues’ regions, highlighting the need to adqueately study brain samples to obtain reliable data concerning the epigenetics of schizophrenia.

  8. Quantitation of normal metabolite concentrations in six brain regions by in-vivo 1 H-MR spectroscopy

    Directory of Open Access Journals (Sweden)

    Minati Ludovico

    2010-01-01

    Full Text Available This study examined the concentrations of brain metabolites visible to in-vivo 1 H-Magnetic Resonance Spectroscopy ( 1 H-MRS at 1.5 T in a sample of 28 normal subjects. Quantitation was attempted for inositol compounds, choline units, total creatine and N-acetyl moieties, using open-source software. Six brain regions were considered: frontal and parietal white matter, medial temporal lobe, thalamus, pons and cerebellum. Absolute concentrations were derived using tissue water as an internal reference and using an external reference; metabolite signal intensity ratios with respect to creatine were also calculated. The inter-individual variability was smaller for absolute concentrations (internal reference as compared to that for signal intensity ratios. Significant regional variability in concentration was found for all metabolites, indicating that separate normative values are needed for different brain regions. The values obtained in this study can be used as reference in future studies, provided the same methodology is followed; it is confirmed that despite unsuccessful attempts in the past, smaller coefficients of variation can indeed be obtained through absolute quantification.

  9. Validating computationally predicted TMS stimulation areas using direct electrical stimulation in patients with brain tumors near precentral regions.

    Science.gov (United States)

    Opitz, Alexander; Zafar, Noman; Bockermann, Volker; Rohde, Veit; Paulus, Walter

    2014-01-01

    The spatial extent of transcranial magnetic stimulation (TMS) is of paramount interest for all studies employing this method. It is generally assumed that the induced electric field is the crucial parameter to determine which cortical regions are excited. While it is difficult to directly measure the electric field, one usually relies on computational models to estimate the electric field distribution. Direct electrical stimulation (DES) is a local brain stimulation method generally considered the gold standard to map structure-function relationships in the brain. Its application is typically limited to patients undergoing brain surgery. In this study we compare the computationally predicted stimulation area in TMS with the DES area in six patients with tumors near precentral regions. We combine a motor evoked potential (MEP) mapping experiment for both TMS and DES with realistic individual finite element method (FEM) simulations of the electric field distribution during TMS and DES. On average, stimulation areas in TMS and DES show an overlap of up to 80%, thus validating our computational physiology approach to estimate TMS excitation volumes. Our results can help in understanding the spatial spread of TMS effects and in optimizing stimulation protocols to more specifically target certain cortical regions based on computational modeling.

  10. Redox proteomic profiling of neuroketal-adducted proteins in human brain: Regional vulnerability at middle age increases in the elderly.

    Science.gov (United States)

    Domínguez, Mayelín; de Oliveira, Eliandre; Odena, María Antonia; Portero, Manuel; Pamplona, Reinald; Ferrer, Isidro

    2016-06-01

    Protein lipoxidation was assessed in the parietal cortex (PC), frontal cortex (FC), and cingulate gyrus (CG) in middle-aged and old-aged individuals with no clinical manifestations of cognitive impairment, in order to increase understanding of regional brain vulnerability to oxidative damage during aging. Twenty-five lipoxidized proteins were identified in all the three regions although with regional specificities, by using redox proteomics to detect target proteins of neuroketals (NKT) adduction. The number of cases with NKT-adducted proteins was higher in old-aged individuals but most oxidized proteins were already present in middle-aged individuals. Differences in vulnerability to oxidation were dependent on the sub-cellular localization, secondary structure, and external exposition of certain amino acids. Lipoxidized proteins included those involved in energy metabolism, cytoskeleton, proteostasis, neurotransmission and O2/CO2, and heme metabolism. Total NKT and soluble oligomer levels were estimated employing slot-blot, and these were compared between age groups. Oligomers increased with age in PC and FC; NKT significantly increased with age in FC, whereas total NKT and oligomer levels were not modified in CG, thus highlighting differences in brain regional vulnerability with age. Oligomers significantly correlated with NKT levels in the three cortical regions, suggesting that protein NKT adduction parallels soluble oligomer formation.

  11. Impact of a single bout of aerobic exercise on regional brain perfusion and activation responses in healthy young adults.

    Directory of Open Access Journals (Sweden)

    Bradley J MacIntosh

    Full Text Available PURPOSE: Despite the generally accepted view that aerobic exercise can have positive effects on brain health, few studies have measured brain responses to exercise over a short time span. The purpose of this study was to examine the impact within one hour of a single bout of exercise on brain perfusion and neuronal activation. METHODS: Healthy adults (n = 16; age range: 20-35 yrs were scanned using Magnetic Resonance Imaging (MRI before and after 20 minutes of exercise at 70% of their age-predicted maximal heart rate. Pseudo-continuous arterial spin labeling (pcASL was used to measure absolute cerebral blood flow (CBF prior to exercise (pre and at 10 min (post-10 and 40 min (post-40 post-exercise. Blood oxygenation level dependent (BOLD functional MRI (fMRI was performed pre and post-exercise to characterize activation differences related to a go/no-go reaction time task. RESULTS: Compared to pre-exercise levels, grey matter CBF was 11% (±9% lower at post-10 (P<0.0004 and not different at post-40 (P = 0.12, while global WM CBF was increased at both time points post-exercise (P<0.0006. Regionally, the hippocampus and insula showed a decrease in perfusion in ROI-analysis at post-10 (P<0.005, FDR corrected, whereas voxel-wise analysis identified elevated perfusion in the left medial postcentral gyrus at post-40 compared to pre (pcorrected = 0.05. BOLD activations were consistent between sessions, however, the left parietal operculum showed reduced BOLD activation after exercise. CONCLUSION: This study provides preliminary evidence of regionalized brain effects associated with a single bout of aerobic exercise. The observed acute cerebrovascular responses may provide some insight into the brain's ability to change in relation to chronic interventions.

  12. Acute and chronic glucocorticoid treatments regulate astrocyte-enriched mRNAs in multiple brain regions in vivo

    Directory of Open Access Journals (Sweden)

    Bradley S. Carter

    2013-08-01

    Full Text Available Previous studies have primarily interpreted gene expression regulation by glucocorticoids in the brain in terms of impact on neurons; however, less is known about the corresponding impact of glucocorticoids on glia and specifically astrocytes in vivo. Recent microarray experiments have identified glucocorticoid-sensitive mRNAs in primary astrocyte cell culture, including a number of mRNAs that have reported astrocyte-enriched expression patterns relative to other brain cell types. Here, we have tested whether elevations of glucocorticoids regulate a subset of these mRNAs in vivo following acute and chronic corticosterone exposure in adult mice. Acute corticosterone exposure was achieved by a single injection of 10 mg/kg corticosterone, and tissue samples were harvested two hours post-injection. Chronic corticosterone exposure was achieved by administering 10 mg/mL corticosterone via drinking water for two weeks. Gene expression was then assessed in two brain regions associated with glucocorticoid action (prefrontal cortex and hippocampus by qPCR and by in situ hybridization. The majority of measured mRNAs regulated by glucocorticoids in astrocytes in vitro were similarly regulated by acute and/or chronic glucocorticoid exposure in vivo. In addition, the expression levels for mRNAs regulated in at least one corticosterone exposure condition (acute/chronic demonstrated moderate positive correlation between the two conditions by brain region. In situ hybridization analyses suggest that select mRNAs are regulated by chronic corticosterone exposure specifically in astroctyes based on (1 similar general expression patterns between corticosterone-treated and vehicle-treated animals and (2 similar expression patterns to the pan-astrocyte marker Aldh1l1. Our findings demonstrate that glucocorticoids regulate astrocyte-enriched mRNAs in vivo and suggest that glucocorticoids regulate gene expression in the brain in a cell type-dependent fashion.

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

    Science.gov (United States)

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

    2015-10-01

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

  14. Brain metabolites in the hippocampus-amygdala region and cerebellum in autism: an {sup 1}H-MR spectroscopy study

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    Otsuka, H.; Harada, M.; Hisaoka, S.; Nishitani, H. [Dept. of Radiology, Univ. of Tokushima, Tokushima City (Japan); Mori, K. [Dept. of Pediatrics, Univ. of Tokushima (Japan)

    1999-07-01

    Histological abnormalities of the brain in autism have been investigated extensively. We studied metabolites in the hippocampusamygdala (HA) region and cerebellum. We examined the right HA region and left cerebellar hemisphere of 27 autistic patients 2-18 years old, 21 boys and 6 girls and 10 normal children 6-14 years old, 4 boys and 6 girls, using the STEAM sequence. This sequence was used to minimise the influence of relaxation times. The N-acetyl aspartate (NAA) concentration was significantly lower (P=0.042) in autistic patients than in normal children (9.37 and 10.95 mM, respectively). There was no significant difference in other metabolites. The correlation coefficient (r value) of NAA between the HA region and cerebellum was 0.616. The decreased NAA concentration may be due to neuronal hypofunction or immature neurons. The NAA concentration in the HA region and cerebellum may be related, because of neuronal circuits or networks. (orig.)

  15. A Cross-Sectional Study of Regional Brain Volume Abnormalities in Lesch-Nyhan Disease and its Variants

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    Schretlen, David J.; Varvaris, Mark; Ho, Tiffany E.; Vannorsdall, Tracy D.; Gordon, Barry; Harris, James C.; Jinnah, H. A.

    2014-01-01

    Background Lesch-Nyhan disease (LND) is a rare, X-linked, neurodevelopmental metabolic disorder that results from a near-complete lack of hypoxanthine phosphoribosyl-transferase enzyme activity. LND is characterized by hyperuricemia, motor neurological abnormalities, recurrent self-injury, and cognitive impairment, but its neural substrates remain poorly understood. Methods In this cross-sectional study, we measured gray matter abnormalities in 21 persons with LND, 17 with an attenuated variant of the phenotype (LNV), and 33 healthy controls using voxel-based morphometry. We conducted an analysis of covariance to identify group differences in regional gray matter volume (GMV), followed by six pair-wise post-hoc group comparisons. Findings Patients with LND showed 20% smaller intracranial volumes (17% gray and 26% white matter) than healthy adults. The largest differences were found in basal ganglia, frontotemporal, and limbic regions, with sparing of parieto-occipital regions. The gray matter volumes of LNV participants invariably fell between those of patients with classical LND and healthy controls. Compared to healthy adults, patients with LND showed additional GMV reductions in the temporal lobe and left lateralized structures, and patients with LNV showed additional reductions in lingual and precuneus regions with sparing of right frontal and temporal regions. LND participants showed reductions in the ventral striatum and prefrontal areas relative to LNV. Interpretation This study of brain morphology reveals regional abnormalities associated with known neurological and behavioral deficits in persons with LND. It also revealed that patients with LNV show milder gray matter abnormalities in many of the same brain regions and preservation of GMV in other regions which could provide important clues to the neural substrates of differences between thephenotypes. PMID:24383089

  16. Regional variations and age-related changes detected with magnetic resonance spectroscopy in the brain of healthy dogs.

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    Ono, Kaori; Kitagawa, Masato; Ito, Daisuke; Tanaka, Natsumi; Watari, Toshihiro

    2014-02-01

    To investigate age-related and regional differences in estimated metabolite concentrations in the brain of healthy dogs by means of magnetic resonance spectroscopy (MRS). 15 healthy Beagles. Dogs were grouped according to age as young (n = 5; all dogs were 2 months old), adult (5; mean age, 4.5 years), or geriatric (5; all dogs were 12 years old). Imaging was performed by use of a 1.5-T MRI system with T1- and T2-weighted spin-echo and fluid-attenuated inversion recovery sequences. Signal intensity measurements for N-acetyl aspartate, creatine, choline, and lactate-alanine (the spectroscopic peaks associated with alanine and lactate could not be reliably differentiated) were determined with MRS, and areas under the spectroscopic peaks (representing concentration estimates) were calculated. Ratios of these metabolite values were compared among age groups and among brain regions with regression analysis. The choline-to-creatine ratio was significantly higher in young dogs, compared with other age groups. The N-acetyl aspartate-to-choline ratio was significantly lower in young dogs and geriatric dogs than in adult dogs. When all age groups were considered, the choline-to-creatine ratio was significantly higher and N-acetyl aspartate-to-choline ratio was significantly lower in the frontal lobe than in all other regions. The N-acetyl aspartate-to-creatine ratio was significantly lower in the cerebellum than in other regions. Metabolite ratios varied significantly among age groups and brain regions in healthy dogs. Future studies should evaluate absolute concentration differences in a larger number of dogs and assess clinical applications in dogs with neurologic diseases.

  17. Exercise increases blood flow to locomotor, vestibular, cardiorespiratory and visual regions of the brain in miniature swine

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    Delp, M. D.; Armstrong, R. B.; Godfrey, D. A.; Laughlin, M. H.; Ross, C. D.; Wilkerson, M. K.

    2001-01-01

    1. The purpose of these experiments was to use radiolabelled microspheres to measure blood flow distribution within the brain, and in particular to areas associated with motor function, maintenance of equilibrium, cardiorespiratory control, vision, hearing and smell, at rest and during exercise in miniature swine. Exercise consisted of steady-state treadmill running at intensities eliciting 70 and 100 % maximal oxygen consumption (V(O(2),max)). 2. Mean arterial pressure was elevated by 17 and 26 % above that at rest during exercise at 70 and 100 % V(O(2),max), respectively. 3. Mean brain blood flow increased 24 and 25 % at 70 and 100 % V(O(2),max), respectively. Blood flow was not locally elevated to cortical regions associated with motor and somatosensory functions during exercise, but was increased to several subcortical areas that are involved in the control of locomotion. 4. Exercise elevated perfusion and diminished vascular resistance in several regions of the brain related to the maintenance of equilibrium (vestibular nuclear area, cerebellar ventral vermis and floccular lobe), cardiorespiratory control (medulla and pons), and vision (dorsal occipital cortex, superior colliculi and lateral geniculate body). Conversely, blood flow to regions related to hearing (cochlear nuclei, inferior colliculi and temporal cortex) and smell (olfactory bulbs and rhinencephalon) were unaltered by exercise and associated with increases in vascular resistance. 5. The data indicate that blood flow increases as a function of exercise intensity to several areas of the brain associated with integrating sensory input and motor output (anterior and dorsal cerebellar vermis) and the maintenance of equilibrium (vestibular nuclei). Additionally, there was an intensity-dependent decrease of vascular resistance in the dorsal cerebellar vermis.

  18. Human embryonic stem cell-derived neurons establish region-specific, long-range projections in the adult brain.

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    Steinbeck, Julius A; Koch, Philipp; Derouiche, Amin; Brüstle, Oliver

    2012-02-01

    While the availability of pluripotent stem cells has opened new prospects for generating neural donor cells for nervous system repair, their capability to integrate with adult brain tissue in a structurally relevant way is still largely unresolved. We addressed the potential of human embryonic stem cell-derived long-term self-renewing neuroepithelial stem cells (lt-NES cells) to establish axonal projections after transplantation into the adult rodent brain. Transgenic and species-specific markers were used to trace the innervation pattern established by transplants in the hippocampus and motor cortex. In vitro, lt-NES cells formed a complex axonal network within several weeks after the initiation of differentiation and expressed a composition of surface receptors known to be instrumental in axonal growth and pathfinding. In vivo, these donor cells adopted projection patterns closely mimicking endogenous projections in two different regions of the adult rodent brain. Hippocampal grafts placed in the dentate gyrus projected to both the ipsilateral and contralateral pyramidal cell layers, while axons of donor neurons placed in the motor cortex extended via the external and internal capsule into the cervical spinal cord and via the corpus callosum into the contralateral cortex. Interestingly, acquisition of these region-specific projection profiles was not correlated with the adoption of a regional phenotype. Upon reaching their destination, human axons established ultrastructural correlates of synaptic connections with host neurons. Together, these data indicate that neurons derived from human pluripotent stem cells are endowed with a remarkable potential to establish orthotopic long-range projections in the adult mammalian brain.

  19. 3-nitropropionic acid-induced mitochondrial permeability transition: comparative study of mitochondria from different tissues and brain regions.

    Science.gov (United States)

    Mirandola, Sandra R; Melo, Daniela R; Saito, Angela; Castilho, Roger F

    2010-02-15

    The adult rat striatum is particularly vulnerable to systemic administration of the succinate dehydrogenase inhibitor 3-nitropropionic acid (3NP), which is known to induce degeneration of the caudate-putamen, as occurs in Huntington's disease. The aim of the present study was to compare the susceptibility of isolated mitochondria from different rat brain regions (striatum, cortex, and cerebellum) as well as from the liver, kidney, and heart to mitochondrial permeability transition (MPT) induced by 3NP and Ca(2+). In the presence of micromolar Ca(2+) concentrations, 3NP induces MPT in a dose-dependent manner, as estimated by mitochondrial swelling and a decrease in the transmembrane electrical potential. A 3NP concentration capable of promoting a 10% inhibition of ADP-stimulated, succinate-supported respiration was sufficient to stimulate Ca(2+)-induced MPT. Brain and heart mitochondria were generally more sensitive to 3NP and Ca(2+)-induced MPT than mitochondria from liver and kidney. In addition, a partial inhibition of mitochondrial respiration by 3NP resulted in more pronounced MPT in striatal mitochondria than in cortical or cerebellar organelles. A similar inhibition of succinate dehydrogenase activity was observed in rat tissue homogenates obtained from various brain regions as well as from liver, kidney, and heart 24 hr after a single i.p. 3NP dose. Mitochondria isolated from forebrains of 3NP-treated rats were also more susceptible to Ca(2+)-induced MPT than those of control rats. We propose that the increased susceptibility of the striatum to 3NP-induced neurodegeneration may be partially explained by its susceptibility to MPT, together with the greater vulnerability of this brain region to glutamate receptor-mediated Ca(2+) influx.

  20. Exercise increases blood flow to locomotor, vestibular, cardiorespiratory and visual regions of the brain in miniature swine

    Science.gov (United States)

    Delp, M. D.; Armstrong, R. B.; Godfrey, D. A.; Laughlin, M. H.; Ross, C. D.; Wilkerson, M. K.

    2001-01-01

    1. The purpose of these experiments was to use radiolabelled microspheres to measure blood flow distribution within the brain, and in particular to areas associated with motor function, maintenance of equilibrium, cardiorespiratory control, vision, hearing and smell, at rest and during exercise in miniature swine. Exercise consisted of steady-state treadmill running at intensities eliciting 70 and 100 % maximal oxygen consumption (V(O(2),max)). 2. Mean arterial pressure was elevated by 17 and 26 % above that at rest during exercise at 70 and 100 % V(O(2),max), respectively. 3. Mean brain blood flow increased 24 and 25 % at 70 and 100 % V(O(2),max), respectively. Blood flow was not locally elevated to cortical regions associated with motor and somatosensory functions during exercise, but was increased to several subcortical areas that are involved in the control of locomotion. 4. Exercise elevated perfusion and diminished vascular resistance in several regions of the brain related to the maintenance of equilibrium (vestibular nuclear area, cerebellar ventral vermis and floccular lobe), cardiorespiratory control (medulla and pons), and vision (dorsal occipital cortex, superior colliculi and lateral geniculate body). Conversely, blood flow to regions related to hearing (cochlear nuclei, inferior colliculi and temporal cortex) and smell (olfactory bulbs and rhinencephalon) were unaltered by exercise and associated with increases in vascular resistance. 5. The data indicate that blood flow increases as a function of exercise intensity to several areas of the brain associated with integrating sensory input and motor output (anterior and dorsal cerebellar vermis) and the maintenance of equilibrium (vestibular nuclei). Additionally, there was an intensity-dependent decrease of vascular resistance in the dorsal cerebellar vermis.

  1. 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.

  2. Therapeutic significance and pharmacological activities of antidiarrheal medicinal plants mention in Ayurveda: A review.

    Science.gov (United States)

    Mishra, Ashish; Seth, Ankit; Maurya, Santosh Kumar

    2016-01-01

    Diarrhea is a serious problem affecting 3-5 billion people per year around the world, especially children of below 5 years. 70% of the world population uses traditional and indigenous medicine for their primary health care. The facts of these indigenous remedies are passed verbally and sometimes as documents. Since ancient time, Ayurveda is the main system of healing in South East Asian countries. Indian literature from ayurvedic texts and other books claim the potency of several plants in the treatment of diarrhea. As the global prospective of ayurvedic medicine is increasing, interest regarding the scientific basis of their action is parallely increasing. Researchers are doing experiments to establish the relation between the claimed action and observed pharmacological activities. In the present article, an attempt was made to compile the scientific basis of medicinal plants used to cure diarrhea in Ayurveda. Literature was collected via electronic search (PubMed, ScienceDirect, Medline, and Google Scholar) from published articles that reports antidiarrheal activity of plants that were mentioned in Ayurveda classics. A total of 109 plant species belonging to 58 families were reported for their antidiarrheal activity. Several Indian medicinal plants have demonstrated promising antidiarrheal effects, but the studies on the antidiarrheal potentials of these plants are not taken beyond proof of concept stage. It is hoped that the article would stimulate future clinical studies because of the paucity of knowledge in this area.

  3. The Use of Recently Developed Histochemical Markers for Localizing Neurotoxicant Induced Regional Brain Pathologies

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    Sumit Sarkar

    2014-04-01

    Full Text Available Neuronal and vascular brain components are interrelated morphologically, physiologically and developmentally. Due to this close interrelationship, it is often difficult to understand the cause and effect relationship between neuronal vs. vascular dysfunction and pathology. This review will discuss four of the more promising recent developments for detecting vascular pathology, and will compare them with the labeling pattern seen with markers of glial and neuronal pathology; following exposure to well characterized neurotoxicants. To detect the vascular dysfunction in the brain, we recently developed a Fluoro-Turquoise gelatin conjugate (FT-gel, a fluorescent probe that helps to delineate between healthy vs. sclerotic vessels. Similarly, we have investigated the potential for Fluoro-Gold to label in vivo all the endothelial cells in the brain as they co-localize with RECA, an endothelial cell marker. We have also developed Amylo-Glo, a fluorescent tracer that can detect neurotoxic A-beta aggregates in the brain. In this article, we will discuss the potential use of these novel histochemical markers to study the neurotoxicant induced brain. We will also discuss neurovascular strategies that may offer novel therapeutic opportunities for neurodegenerative disorders.

  4. Analysis of Alzheimer's disease severity across brain regions by topological analysis of gene co-expression networks

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    Zhang Weixiong

    2010-10-01

    Full Text Available Abstract Background Alzheimer's disease (AD is a progressive neurodegenerative disorder involving variations in the transcriptome of many genes. AD does not affect all brain regions simultaneously. Identifying the differences among the affected regions may shed more light onto the disease progression. We developed a novel method involving the differential topology of gene coexpression networks to understand the association among affected regions and disease severity. Methods We analysed microarray data of four regions - entorhinal cortex (EC, hippocampus (HIP, posterior cingulate cortex (PCC and middle temporal gyrus (MTG from AD affected and normal subjects. A coexpression network was built for each region and the topological overlap between them was examined. Genes with zero topological overlap between two region-specific networks were used to characterise the differences between the two regions. Results and conclusion Results indicate that MTG shows early AD pathology compared to the other regions. We postulate that if the MTG gets affected later in the disease, post-mortem analyses of individuals with end-stage AD will show signs of early AD in the MTG, while the EC, HIP and PCC will have severe pathology. Such knowledge is useful for data collection in clinical studies where sample selection is a limiting factor as well as highlighting the underlying biology of disease progression.

  5. Somatosensory Brain Function and Gray Matter Regional Volumes Differ According to Exercise History: Evidence from Monozygotic Twins.

    Science.gov (United States)

    Hautasaari, Pekka; Savić, Andrej M; Loberg, Otto; Niskanen, Eini; Kaprio, Jaakko; Kujala, Urho M; Tarkka, Ina M

    2017-01-01

    Associations between long-term physical activity and cortical function and brain structure are poorly known. Our aim was to assess whether brain functional and/or structural modulation associated with long-term physical activity is detectable using a discordant monozygotic male twin pair design. Nine monozygotic male twin pairs were carefully selected for an intrapair difference in their leisure-time physical activity of at least three years duration (mean age 34 ± 1 years). We registered somatosensory mismatch response (SMMR) in EEG to electrical stimulation of fingers and whole brain MR images. We obtained exercise history and measured physical fitness and body composition. Equivalent electrical dipole sources of SMMR as well as gray matter (GM) voxel counts in regions of interest indicated by source analysis were evaluated. SMMR dipolar source strengths differed between active and inactive twins within twin pairs in postcentral gyrus, medial frontal gyrus and superior temporal gyrus and in anterior cingulate (AC) GM voxel counts differed similarly. Compared to active twins, their inactive twin brothers showed greater dipole strengths in short periods of the deviant-elicited SMMR and larger AC GM voxel counts. Stronger activation in early unattended cortical processing of the deviant sensory signals in inactive co-twins may imply less effective gating of somatosensory information in inactive twins compared to their active brothers. Present findings indicate that already in 30's long-term physical activity pattern is linked with specific brain indices, both in functional and structural domains.

  6. Microbiome-Derived Lipopolysaccharide Enriched in the Perinuclear Region of Alzheimer’s Disease Brain

    Directory of Open Access Journals (Sweden)

    Yuhai Zhao

    2017-09-01

    Full Text Available Abundant clinical, epidemiological, imaging, genetic, molecular, and pathophysiological data together indicate that there occur an unusual inflammatory reaction and a disruption of the innate-immune signaling system in Alzheimer’s disease (AD brain. Despite many years of intense study, the origin and molecular mechanics of these AD-relevant pathogenic signals are still not well understood. Here, we provide evidence that an intensely pro-inflammatory bacterial lipopolysaccharide (LPS, part of a complex mixture of pro-inflammatory neurotoxins arising from abundant Gram-negative bacilli of the human gastrointestinal (GI tract, are abundant in AD-affected brain neocortex and hippocampus. For the first time, we provide evidence that LPS immunohistochemical signals appear to aggregate in clumps in the parenchyma in control brains, and in AD, about 75% of anti-LPS signals were clustered around the periphery of DAPI-stained nuclei. As LPS is an abundant secretory product of Gram-negative bacilli resident in the human GI-tract, these observations suggest (i that a major source of pro-inflammatory signals in AD brain may originate from internally derived noxious exudates of the GI-tract microbiome; (ii that due to aging, vascular deficits or degenerative disease these neurotoxic molecules may “leak” into the systemic circulation, cerebral vasculature, and on into the brain; and (iii that this internal source of microbiome-derived neurotoxins may play a particularly strong role in shaping the human immune system and contributing to neural degeneration, particularly in the aging CNS. This “Perspectives” paper will further highlight some very recent developments that implicate GI-tract microbiome-derived LPS as an important contributor to inflammatory-neurodegeneration in the AD brain.

  7. Allometric scaling of brain regions to intra-cranial volume: An epidemiological MRI study.

    Science.gov (United States)

    de Jong, Laura W; Vidal, Jean-Sébastien; Forsberg, Lars E; Zijdenbos, Alex P; Haight, Thaddeus; Sigurdsson, Sigurdur; Gudnason, Vilmundur; van Buchem, Mark A; Launer, Lenore J

    2017-01-01

    There is growing evidence that sub-structures of the brain scale allometrically to total brain size, that is, in a non-proportional and non-linear way. Here, scaling of different volumes of interest (VOI) to intra-cranial volume (ICV) was examined. It was assessed whether scaling was allometric or isometric and whether scaling coefficients significantly differed from each other. We also tested to what extent allometric scaling of VOI was introduced by the automated segmentation technique. Furthermore, reproducibility of allometric scaling was studied different age groups and study populations. Study samples included samples of cognitively healthy adults from the community-based Age Gene/Environment Susceptibility-Reykjavik Study (AGES-Reykjavik Study) (N = 3,883), the Coronary Artery Risk Development in Young Adults Study (CARDIA) (N =709), and the Alzheimer's Disease Neuroimaging Initiative (ADNI) (N = 180). Data encompassed participants with different age, ethnicity, risk factor profile, and ICV and VOI obtained with different automated MRI segmentation techniques. Our analysis showed that (1) allometric scaling is a trait of all parts of the brain, (2) scaling of neo-cortical white matter, neo-cortical gray matter, and deep gray matter structures including the cerebellum are significantly different from each other, and (3) allometric scaling of brain structures cannot solely be explained by age-associated atrophy, sex, ethnicity, or a systematic bias from study-specific segmentation algorithm, but appears to be a true feature of brain geometry. Hum Brain Mapp 38:151-164, 2017. © 2016 Wiley Periodicals, Inc.

  8. Regional white matter volume and the relation with attentional functioning in survivors of malignant pediatric brain tumors

    Science.gov (United States)

    Glass, John O.; Mulhern, Raymond K.; White, Holly A.; Wilkinson, Gina M.; Reddick, Wilburn E.

    2003-05-01

    Quantitative assessment of MR examinations in 37 survivors of childhood cancer treated with central nervous system prophylaxis revealed that normal appearing white matter (NAWM) volume is associated with attention-related problems, localized specifically in the right prefrontal region. T1-, T2-, and PD-weighted images were segmented and divided into pre-frontal, frontal, parietal/temporal, and parietal/occipital regions for each hemisphere. These eight regions were analyzed in five slices centered at the level of the basal ganglia. The patient's age at diagnosis and time elapsed from diagnosis were used as covariates in the regressions. Attentional measures showed significant deficiency when compared to age and gender normative values. Total, frontal and/or prefrontal NAWM volumes from the range of slices examined were significantly associated with 5 of the 8 attentional measures. The frontal/prefrontal region of the brain is associated with executive functioning tasks and could potentially be spared as much as possible during therapy planning. The results of the present study further support the contention that NAWM is an important substrate for treatment-induced neurocognitive problems among survivors of malignant brain tumors of childhood.

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

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    Golarai, Golijeh; Ghahremani, Dara G; Eberhardt, Jennifer L; Gabrieli, John D E

    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 rearranged. Response amplitudes were reduced in the AMG and STS when subjects viewed stimuli whose configuration of parts were digitally rearranged, suggesting that these regions represent 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.

  10. The antioxidant effect of astaxanthin is higher in young mice than aged: a region specific study on brain.

    Science.gov (United States)

    Al-Amin, Md Mamun; Akhter, Samiha; Hasan, Ahmed Tasdid; Alam, Tanzir; Nageeb Hasan, S M; Saifullah, A R M; Shohel, Mohammad

    2015-10-01

    Astaxanthin is a potential antioxidant which shows neuroprotective property. We aimed to investigate the age-dependent and region-specific antioxidant effects of astaxanthin in mice brain. Animals were divided into 4 groups; treatment young (3 months, n = 6) (AY), treatment old (16 months, n = 6) (AO), placebo young (3 months, n = 6) (PY) and placebo old (16 months, n = 6) (PO) groups. Treatment group was given astaxanthin (2 mg/kg/day, body weight), and placebo group was given 100 μl of 0.9% normal saline orally to the healthy Swiss albino mice for 4 weeks. The level of non-enzymatic oxidative markers namely malondialdehyde (MDA); nitric oxide (NO); advanced protein oxidation product (APOP); glutathione (GSH) and the activity of enzymatic antioxidants i.e.; catalase (CAT) and superoxide dismutase (SOD) were determined from the isolated brain regions. Treatment with astaxanthin significantly (p Astaxanthin markedly (p astaxanthin is age-dependent, higher in young in compared to the aged brain.

  11. Decreased resting state metabolic activity in frontopolar and parietal brain regions is associated with suicide plans in depressed individuals.

    Science.gov (United States)

    van Heeringen, Kees; Wu, Guo-Rong; Vervaet, Myriam; Vanderhasselt, Marie-Anne; Baeken, Chris

    2017-01-01

    Suicide plans are a major risk factor for suicide, which is a devastating outcome of depression. While structural and functional brain changes have been demonstrated in relation to suicidal thoughts and behaviour, brain mechanisms underlying suicide plans have not yet been studied. Here, we studied changes in regional cerebral metabolic activity in association with suicide plans in depressed individuals. Using (18)FDG-PET, a comparative study of regional cerebral glucose metabolism (rCMRglu) was carried out in depressed individuals with suicidal thoughts and suicide plans, depressed individuals with only suicidal thoughts, depressed individuals without suicide thoughts and plans, and healthy controls. When compared to the other groups, depressed individuals with suicide plans showed relative hypometabolism in the right middle frontal gyrus and the right inferior parietal lobe (Brodmann areas 10 and 39). Suicide plans in depressed individuals appear to be associated with reduced activity in brain areas that are involved in decision-making and choice, more particularly in exploratory behaviour. Copyright © 2016 Elsevier Ltd. All rights reserved.

  12. Projections from a single NUCB2/nesfatin-1 neuron in the paraventricular nucleus to different brain regions involved in feeding.

    Science.gov (United States)

    Maejima, Yuko; Kumamoto, Kensuke; Takenoshita, Seiichi; Shimomura, Kenju

    2016-12-01

    The anorexigenic neuropeptide NEFA/nucleobindin 2 (NUCB2)/nesfatin-1-containing neurons are distributed in the brain regions involved in feeding regulation, including the hypothalamic paraventricular nucleus (PVN). Functionally, NUCB2/nesfatin-1 neurons in the PVN regulate feeding through the hypothalamus and brain stem. However, the neural network of PVN NUCB2/nesfatin-1 neurons has yet to be elucidated. Axon collateral branches allow individual neurons to target multiple neurons. In some cases, each target neuron can be located in different nuclei. Here we show that a single neuron in the PVN projects axonal collaterals to both the dorsal vagal complex (DVC) and the arcuate nucleus (ARC), which are important brain regions for feeding regulation. In this study, after injection of different retrograde tracers into the DVC and ARC, both tracer-labeled neurons were detected in the identical PVN neuron, indicating the axon collateral projections from the single PVN neuron to the DVC and ARC. Furthermore, immunohistochemical analysis revealed that approximately 50 % of the neurons with axon collateral projections from the PVN to the DVC and ARC were found to be NUCB2/nesfatin-1 neurons. Our data suggest that a single NUCB2/nesfatin-1 neuron in the PVN projects to both the ARC and the DVC with axon collateral projection. Although the physiological significance remains to be elucidated, our data offer new perspectives on NUCB2/nesfatin-1 function at the neural network level and food intake regulation.

  13. Regional Homogeneity of Resting-State Brain Activity Suppresses the Effect of Dopamine-Related Genes on Sensory Processing Sensitivity.

    Directory of Open Access Journals (Sweden)

    Chunhui Chen

    Full Text Available Sensory processing sensitivity (SPS is an intrinsic personality trait whose genetic and neural bases have recently been studied. The current study used a neural mediation model to explore whether resting-state brain functions mediated the effects of dopamine-related genes on SPS. 298 healthy Chinese college students (96 males, mean age = 20.42 years, SD = 0.89 were scanned with magnetic resonance imaging during resting state, genotyped for 98 loci within the dopamine system, and administered the Highly Sensitive Person Scale. We extracted a "gene score" that summarized the genetic variations representing the 10 loci that were significantly linked to SPS, and then used path analysis to search for brain regions whose resting-state data would help explain the gene-behavior association. Mediation analysis revealed that temporal homogeneity of regional spontaneous activity (ReHo in the precuneus actually suppressed the effect of dopamine-related genes on SPS. The path model explained 16% of the variance of SPS. This study represents the first attempt at using a multi-gene voxel-based neural mediation model to explore the complex relations among genes, brain, and personality.

  14. Toluene effects on oxidative stress in brain regions of young-adult, middle-age, and senescent Brown Norway rats

    Energy Technology Data Exchange (ETDEWEB)

    Kodavanti, Prasada Rao S., E-mail: kodavanti.prasada@epa.gov [Neurotoxicology Branch, Toxicity Assessment Division, NHEERL, ORD, U.S. Environmental Protection Agency, Research Triangle Park, NC 27711 (United States); Royland, Joyce E. [Genetic and Cellular Toxicology Branch, Integrated Systems Toxicology Division, NHEERL, ORD, U.S. Environmental Protection Agency, Research Triangle Park, NC 27711 (United States); Richards, Judy E. [Research Core Unit, NHEERL, ORD, U.S. Environmental Protection Agency, Research Triangle Park, NC 27711 (United States); Besas, Jonathan; MacPhail, Robert C. [Neurotoxicology Branch, Toxicity Assessment Division, NHEERL, ORD, U.S. Environmental Protection Agency, Research Triangle Park, NC 27711 (United States)

    2011-11-15

    The influence of aging on susceptibility to environmental contaminants is not well understood. To extend knowledge in this area, we examined effects in rat brain of the volatile organic compound, toluene. The objective was to test whether oxidative stress (OS) plays a role in the adverse effects caused by toluene exposure, and if so, if effects are age-dependent. OS parameters were selected to measure the production of reactive oxygen species (NADPH Quinone oxidoreductase 1 (NQO1), NADH Ubiquinone reductase (UBIQ-RD)), antioxidant homeostasis (total antioxidant substances (TAS), superoxide dismutase (SOD), {gamma}-glutamylcysteine synthetase ({gamma}-GCS), glutathione transferase (GST), glutathione peroxidase (GPX), glutathione reductase (GRD)), and oxidative damage (total aconitase and protein carbonyls). In this study, Brown Norway rats (4, 12, and 24 months) were dosed orally with toluene (0, 0.65 or 1 g/kg) in corn oil. Four hours later, frontal cortex, cerebellum, striatum, and hippocampus were dissected, quick frozen on dry ice, and stored at - 80 Degree-Sign C until analysis. Some parameters of OS were found to increase with age in select brain regions. Toluene exposure also resulted in increased OS in select brain regions. For example, an increase in NQO1 activity was seen in frontal cortex and cerebellum of 4 and 12 month old rats following toluene exposure, but only in the hippocampus of 24 month old rats. Similarly, age and toluene effects on glutathione enzymes were varied and brain-region specific. Markers of oxidative damage reflected changes in oxidative stress. Total aconitase activity was increased by toluene in frontal cortex and cerebellum at 12 and 24 months, respectively. Protein carbonyls in both brain regions and in all age groups were increased by toluene, but step-down analyses indicated toluene effects were statistically significant only in 12 month old rats. These results indicate changes in OS parameters with age and toluene exposure

  15. In vivo changes in microglial activation and amyloid deposits in brain regions with hypometabolism in Alzheimer's disease

    Energy Technology Data Exchange (ETDEWEB)

    Yokokura, Masamichi; Mori, Norio; Yoshihara, Yujiro; Wakuda, Tomoyasu; Takebayashi, Kiyokazu; Iwata, Yasuhide; Nakamura, Kazuhiko [Hamamatsu University School of Medicine, Department of Psychiatry and Neurology, Hamamatsu (Japan); Yagi, Shunsuke; Ouchi, Yasuomi [Hamamatsu University School of Medicine, Laboratory of Human Imaging Research, Molecular Imaging Frontier Research Center, Hamamatsu (Japan); Yoshikawa, Etsuji [Hamamatsu Photonics K.K., Central Research Laboratory, Hamamatsu (Japan); Kikuchi, Mitsuru [Kanazawa University, Department of Psychiatry and Neurobiology, Graduate School of Medical Science, Kanazawa (Japan); Sugihara, Genichi; Suda, Shiro; Tsuchiya, Kenji J.; Suzuki, Katsuaki [Hamamatsu University School of Medicine, Research Center for Child Mental Development, Hamamatsu (Japan); Ueki, Takatoshi [Hamamatsu University School of Medicine, Department of Anatomy, Hamamatsu (Japan)

    2011-02-15

    Amyloid {beta} protein (A{beta}) is known as a pathological substance in Alzheimer's disease (AD) and is assumed to coexist with a degree of activated microglia in the brain. However, it remains unclear whether these two events occur in parallel with characteristic hypometabolism in AD in vivo. The purpose of the present study was to clarify the in vivo relationship between A{beta} accumulation and neuroinflammation in those specific brain regions in early AD. Eleven nootropic drug-naive AD patients underwent a series of positron emission tomography (PET) measurements with [{sup 11}C](R)PK11195, [{sup 11}C]PIB and [{sup 18}F]FDG and a battery of cognitive tests within the same day. The binding potentials (BPs) of [{sup 11}C](R)PK11195 were directly compared with those of [{sup 11}C]PIB in the brain regions with reduced glucose metabolism. BPs of [{sup 11}C](R)PK11195 and [{sup 11}C]PIB were significantly higher in the parietotemporal regions of AD patients than in ten healthy controls. In AD patients, there was a negative correlation between dementia score and [{sup 11}C](R)PK11195 BPs, but not [{sup 11}C]PIB, in the limbic, precuneus and prefrontal regions. Direct comparisons showed a significant negative correlation between [{sup 11}C](R)PK11195 and [{sup 11}C]PIB BPs in the posterior cingulate cortex (PCC) (p < 0.05, corrected) that manifested the most severe reduction in [{sup 18}F]FDG uptake. A lack of coupling between microglial activation and amyloid deposits may indicate that A{beta} accumulation shown by [{sup 11}C]PIB is not always the primary cause of microglial activation, but rather the negative correlation present in the PCC suggests that microglia can show higher activation during the production of A{beta} in early AD. (orig.)

  16. Simultaneous quantification of monoamine neurotransmitters and their biogenic metabolites intracellularly and extracellularly in primary neuronal cell cultures and in sub-regions of guinea pig brain

    DEFF Research Database (Denmark)

    Schou-Pedersen, Anne Marie Voigt; Hansen, Stine Normann; Tveden-Nyborg, Pernille

    2016-01-01

    In the present paper, we describe a validated chromatographic method for the simultaneous quantification of monoamine neurotransmitters and their biogenic metabolites intracellularly and extracellularly in primary neuronal cell culture and in sub-regions of the guinea pig brain. Electrochemical d...... and is broadly applicable to monoamine measurements in cell cultures as well as brain biopsies from animal models used in preclinical neurochemistry....

  17. Identification of brain regions predicting epileptogenesis by serial [18F]GE-180 positron emission tomography imaging of neuroinflammation in a rat model of temporal lobe epilepsy

    Directory of Open Access Journals (Sweden)

    Vera Russmann

    2017-01-01

    In conclusion, the data provide evidence that [18F]GE-180 PET brain imaging can serve as a biomarker of epileptogenesis. The identification of brain regions with predictive value might facilitate the development of preventive concepts as well as the early assessment of the interventional success. Future studies are necessary to further confirm the predictivity of the approach.

  18. Radiotherapy of primary brain tumours in the region of the third ventricle

    NARCIS (Netherlands)

    Heesters, M A; Struikmans, H

    1990-01-01

    Patients (n = 18) with a primary brain tumour near the third ventricle and treated by radiotherapy were retrospectively analysed. Four different subgroups of patients, according to the histology (germ cell tumours, astrocytomas, other histologies, no histology) were separately discussed. Third ventr

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

    DEFF Research Database (Denmark)

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

    2014-01-01

    BACKGROUND:Alzheimer's disease (AD) is a progressive, incurable neurodegenerative disease and the most common type of dementia. It cannot be prevented, cured or drastically slowed, even though AD research has increased in the past 5-10 years. Instead of focusing on the brain volume or on the single...

  20. Are Autistic Traits in the General Population Related to Global and Regional Brain Differences?

    Science.gov (United States)

    Koolschijn, P. Cédric M. P.; Geurts, Hilde M.; van der Leij, Andries R.; Scholte, H. Steven

    2015-01-01

    There is accumulating evidence that autistic-related traits in the general population lie on a continuum, with autism spectrum disorders representing the extreme end of this distribution. Here, we tested the hypothesis of a possible relationship between autistic traits and brain morphometry in the general population. Participants completed the…

  1. protein-profiles-of-serum-brain-regions-and-hypophyses-of-pubertal ...

    African Journals Online (AJOL)

    In a completely randomized design, each group of the ... analysis. All the animals were slaughtered and the brains and the hypophyses were carefully dissected out to determine the ... reduced tissue protein synthesis (Dänicke et al., .... evaluation of serum proteins at the Chemical .... processes, including metabolism and.

  2. Induction of brain region-specific forms of obesity by Agouti

    NARCIS (Netherlands)

    Kas, M.J.H.; Tiesjema, B; van Dijk, G; Garner, KM; Barsh, GS; Ter Brake, O; Verhaagen, J; Adan, RAH

    2004-01-01

    Disruption of melanocortin ( MC) signaling, such as by ectopic Agouti overexpression, leads to an obesity syndrome with hyperphagia, obesity, and accelerated body weight gain during high-fat diet. To investigate where in the brain disruption of MC signaling results in obesity, long-term Agouti expre

  3. Induction of brain-region-specific forms of obesity by agouti

    NARCIS (Netherlands)

    Kas, Martien J H; Tiesjema, Birgitte; van Dijk, Gertjan; Garner, Keith M; Barsh, Gregory S; ter Brake, Olivier; Verhaagen, Joost; Adan, Roger A H

    2004-01-01

    Disruption of melanocortin (MC) signaling, such as by ectopic Agouti overexpression, leads to an obesity syndrome with hyperphagia, obesity, and accelerated body weight gain during high-fat diet. To investigate where in the brain disruption of MC signaling results in obesity, long-term Agouti expres

  4. Induction of brain region-specific forms of obesity by Agouti

    NARCIS (Netherlands)

    Kas, M.J.H.; Tiesjema, B; van Dijk, G; Garner, KM; Barsh, GS; Ter Brake, O; Verhaagen, J; Adan, RAH

    2004-01-01

    Disruption of melanocortin ( MC) signaling, such as by ectopic Agouti overexpression, leads to an obesity syndrome with hyperphagia, obesity, and accelerated body weight gain during high-fat diet. To investigate where in the brain disruption of MC signaling results in obesity, long-term Agouti

  5. Regional localization of halopemide, a new psychotropic agent, in the rat brain

    NARCIS (Netherlands)

    Loonen, A.J.M.; Van Wijngaarden, I.; Janssen, P.A.J.; Soudijn, W.

    1978-01-01

    Halopemide is a new psychotropic agent, structurally related to the neuroleptics of the butyrophenone type, but with a different pharmacological and clinical profile. The concentration of halopemide in the rat brain is about 10 times less than that of R 29800, its chemical congener and of spiperone,

  6. Fully automated rodent brain MR image processing pipeline on a Midas server: from acquired images to region-based statistics.

    Science.gov (United States)

    Budin, Francois; Hoogstoel, Marion; Reynolds, Patrick; Grauer, Michael; O'Leary-Moore, Shonagh K; Oguz, Ipek

    2013-01-01

    Magnetic resonance imaging (MRI) of rodent brains enables study of the development and the integrity of the brain under certain conditions (alcohol, drugs etc.). However, these images are difficult to analyze for biomedical researchers with limited image processing experience. In this paper we present an image processing pipeline running on a Midas server, a web-based data storage system. It is composed of the following steps: rigid registration, skull-stripping, average computation, average parcellation, parcellation propagation to individual subjects, and computation of region-based statistics on each image. The pipeline is easy to configure and requires very little image processing knowledge. We present results obtained by processing a data set using this pipeline and demonstrate how this pipeline can be used to find differences between populations.

  7. Regional susceptibility to TNF-α induction of murine brain inflammation via classical IKK/NF-κB signalling.

    Directory of Open Access Journals (Sweden)

    Adam M H Young

    Full Text Available It is becoming clear that inflammation plays a significant role in a number of neurological and psychiatric conditions. Post mortem brain samples in Alzheimer's disease, Parkinson's disease, amyotrophic lateral sclerosis, multiple sclerosis, schizophrenia and most recently autism spectrum condition, all exhibit neuroglial activation and inflammatory markers within the CSF. Many questions remain about the underlying molecular mechanisms. By adding the pro-inflammatory cytokine, TNF-α, to mouse brain tissue we demonstrated that the frontal lobes and temporal region, areas involved in higher functions such as memory and learning, are most susceptible to cytokine-induced inflammation via the NF-κB signalling pathway. We observed direct correlations between the volumetric increase and molecular expression indicating that therapeutic targets in these lobes may require different approaches when treating conditions with a central neuroinflammatory component.

  8. Multiple sclerosis patients lacking oligoclonal bands in the cerebrospinal fluid have less global and regional brain atrophy.

    Science.gov (United States)

    Ferreira, Daniel; Voevodskaya, Olga; Imrell, Kerstin; Stawiarz, Leszek; Spulber, Gabriela; Wahlund, Lars-Olof; Hillert, Jan; Westman, Eric; Karrenbauer, Virginija Danylaité

    2014-09-15

    To investigate whether multiple sclerosis (MS) patients with and without cerebrospinal fluid (CSF) oligoclonal immunoglobulin G bands (OCB) differ in brain atrophy. Twenty-eight OCB-negative and thirty-five OCB-positive patients were included. Larger volumes of total CSF and white matter (WM) lesions; smaller gray matter (GM) volume in the basal ganglia, diencephalon, cerebellum, and hippocampus; and smaller WM volume in corpus callosum, periventricular-deep WM, brainstem, and cerebellum, were observed in OCB-positives. OCB-negative patients, known to differ genetically from OCB-positives, are characterized by less global and regional brain atrophy. This finding supports the notion that OCB-negative MS patients may represent a clinically relevant MS subgroup. Copyright © 2014 Elsevier B.V. All rights reserved.

  9. Mapping patterns of depression-related brain regions with cytochrome oxidase histochemistry: relevance of animal affective systems to human disorders, with a focus on resilience to adverse events.

    Science.gov (United States)

    Harro, Jaanus; Kanarik, Margus; Matrov, Denis; Panksepp, Jaak

    2011-10-01

    The search for novel antidepressants may be facilitated by pre-clinical animal models that relay on specific neural circuit and related neurochemical endpoint measures, which are anchored in concrete neuro-anatomical and functional neural-network analyzes. One of the most important initial considerations must be which regions of the brain are candidates for the maladaptive response to depressogenic challenges. Consideration of persistent differences or changes in the activity of cerebral networks can be achieved by mapping oxidative metabolism in ethologically or pathogenetically relevant animal models. Cytochrome oxidase histochemistry is a technique suitable to detect regional long-term brain activity changes relative to control conditions and has been used in a variety of animal models. This work is summarized and indicates that major changes occur mainly in subcortical areas, highlighting specific brain regions where some alterations in regional oxidative metabolism may represent adaptive changes to depressogenic adverse life events, while others may reflect failures of adaptation. Many of these changes in oxidative metabolism may depend upon the integrity of serotonergic neurotransmission, and occur in several brain regions shown by other techniques to be involved in endogenous affective circuits that control emotional behaviors as well as related higher brain regions that integrate learning and cognitive information processing. These brain regions appear as primary targets for further identification of endophenotypes specific to affective disorders.

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

    Directory of Open Access Journals (Sweden)

    Lumei Liu

    2016-07-01

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

  11. The timing and strength of regional brain activation associated with word recognition in children with reading difficulties

    Directory of Open Access Journals (Sweden)

    Roozbeh eRezaie

    2011-05-01

    Full Text Available The study investigates the relative degree and timing of cortical activation across parietal, temporal, and frontal regions during performance of a continuous visual word recognition task in children who experience reading difficulties (N=44, RD and typical readers (N=40, NI. Minimum norm estimates of regional neurophysiological activity were obtained from magnetoencephalographic recordings. Children with RD showed bilaterally reduced neurophysiological activity in the superior and middle temporal gyri, and increased activity in rostral middle frontal and ventral occipitotemporal cortices, bilaterally. The temporal profile of activity in the RD group, featured near-simultaneous activity peaks in temporal, inferior parietal and prefrontal regions, in contrast to a clear temporal progression of activity among these areas in the NI group. These results replicate and extend previous MEG and fMRI results demonstrating atypical, latency-dependent attributes of the brain circuit involved in word reading in children with reading difficulties.

  12. HIV DNA in CD14+ Reservoirs is Associated with Regional Brain Atrophy in cART-Naïve Patients

    Science.gov (United States)

    Kallianpur, Kalpana J.; Valcour, Victor G.; Lerdlum, Sukalaya; Busovaca, Edgar; Agsalda, Melissa; Sithinamsuwan, Pasiri; Chalermchai, Thep; Fletcher, James L.K.; Tipsuk, Somporn; Shikuma, Cecilia M.; Shiramizu, Bruce T.; Ananworanich, Jintanat

    2014-01-01

    Objective To examine associations between regional brain volumes and HIV DNA in peripheral CD14+ cells (monocytes) among HIV-infected individuals naïve to combination antiretroviral therapy (cART). Design A prospective study of HIV-infected Thai individuals who met Thai national criteria for cART initiation. Enrollment was stratified by HIV DNA in a blinded fashion. Methods CD14+ cells were isolated from peripheral mononuclear cells to high purity (median 91.4% monocytes by flow cytometry), and HIV DNA was quantified by multiplex real-time PCR. Baseline regional brain volumes obtained by T1-weighted 1.5-Tesla magnetic resonance imaging were compared between HIV DNA groups using analysis of covariance (ANCOVA). Results We studied 60 subjects with mean (SD) age of 34.7 (7.0) years, CD4 T-lymphocyte count of 232 (137) cells/mm3, and log10 plasma HIV RNA of 4.8 (0.73). Median (IQR) HIV DNA copy number per 106 CD14+ cells was 54 (102). Using our previously determined optimal cut-point of 45 copies/106 cells for this cohort, a threshold value above which CD14+ HIV DNA identified HIV-associated neurocognitive disorders (HAND), we found that CD14+ HIV DNA ≥ 45 copies/106 cells was associated with reduced volumes of the nucleus accumbens (p = 0.021), brainstem (p = 0.033) and total gray matter (p = 0.045) independently of age, CD4 count and intracranial volume. Conclusion HIV DNA burden in CD14+ monocytes is directly linked to brain volumetric loss. Our findings implicate peripheral viral reservoirs in HIV-associated brain atrophy and support their involvement in the neuropathogenesis of HAND, underscoring the need for therapies that target these cells. PMID:25232899

  13. Cardiac Arrest Alters Regional Ubiquitin Levels in Association with the Blood-Brain Barrier Breakdown and Neuronal Damages in the Porcine Brain.

    Science.gov (United States)

    Sharma, Hari S; Patnaik, Ranjana; Sharma, Aruna; Lafuente, José Vicente; Miclescu, Adriana; Wiklund, Lars

    2015-10-01

    The possibility that ubiquitin expression is altered in cardiac arrest-associated neuropathology was examined in a porcine model using immunohistochemical and biochemical methods. Our observations show that cardiac arrest induces progressive increase in ubiquitin expression in the cortex and hippocampus in a selective and specific manner as compared to corresponding control brains using enzyme-linked immunoassay technique (enzyme-linked immunosorbent assay (ELISA)). Furthermore, immunohistochemical studies showed ubiquitin expression in the neurons exhibiting immunoreaction in the cytoplasm and karyoplasm of distorted or damaged cells. Separate Nissl and ubiquitin staining showed damaged and distorted neurons and in the same cortical region ubiquitin expression indicating that ubiquitin expression after cardiac arrest represents dying neurons. The finding that methylene blue treatment markedly induced neuroprotection following identical cardiac arrest and reduced ubiquitin expression strengthens this view. Taken together, our observations are the first to show that cardiac arrest enhanced ubiquitin expression in the brain that is related to the magnitude of neuronal injury and the finding that methylene blue reduced ubiquitin expression points to its role in cell damage, not reported earlier.

  14. Brain region-specific alterations in the gene expression of cytokines, immune cell markers and cholinergic system components during peripheral endotoxin-induced inflammation.

    Science.gov (United States)

    Silverman, Harold A; Dancho, Meghan; Regnier-Golanov, Angelique; Nasim, Mansoor; Ochani, Mahendar; Olofsson, Peder S; Ahmed, Mohamed; Miller, Edmund J; Chavan, Sangeeta S; Golanov, Eugene; Metz, Christine N; Tracey, Kevin J; Pavlov, Valentin A

    2015-03-11

    Inflammatory conditions characterized by excessive peripheral immune responses are associated with diverse alterations in brain function, and brain-derived neural pathways regulate peripheral inflammation. Important aspects of this bidirectional peripheral immune-brain communication, including the impact of peripheral inflammation on brain region-specific cytokine responses, and brain cholinergic signaling (which plays a role in controlling peripheral cytokine levels), remain unclear. To provide insight, we studied gene expression of cytokines, immune cell markers and brain cholinergic system components in the cortex, cerebellum, brainstem, hippocampus, hypothalamus, striatum and thalamus in mice after an intraperitoneal lipopolysaccharide injection. Endotoxemia was accompanied by elevated serum levels of interleukin (IL)-1β, IL-6 and other cytokines and brain region-specific increases in Il1b (the highest increase, relative to basal level, was in cortex; the lowest increase was in cerebellum) and Il6 (highest increase in cerebellum; lowest increase in striatum) mRNA expression. Gene expression of brain Gfap (astrocyte marker) was also differentially increased. However, Iba1 (microglia marker) mRNA expression was decreased in the cortex, hippocampus and other brain regions in parallel with morphological changes, indicating microglia activation. Brain choline acetyltransferase (Chat ) mRNA expression was decreased in the striatum, acetylcholinesterase (Ache) mRNA expression was decreased in the cortex and increased in the hippocampus, and M1 muscarinic acetylcholine receptor (Chrm1) mRNA expression was decreased in the cortex and the brainstem. These results reveal a previously unrecognized regional specificity in brain immunoregulatory and cholinergic system gene expression in the context of peripheral inflammation and are of interest for designing future antiinflammatory approaches.

  15. Brain Basics

    Medline Plus

    Full Text Available ... brain may play a role in disorders like schizophrenia or attention deficit hyperactivity disorder (ADHD) . Glutamate —the ... mental disorders, including autism , obsessive compulsive disorder (OCD) , schizophrenia , and depression . Brain Regions Just as many neurons ...

  16. Expertise modulates local regional homogeneity of spontaneous brain activity in the resting brain: an fMRI study using the model of skilled acupuncturists.

    Science.gov (United States)

    Dong, Minghao; Qin, Wei; Zhao, Ling; Yang, Xuejuan; Yuan, Kai; Zeng, Fang; Sun, Jinbo; Yu, Dahua; von Deneen, Karen M; Liang, Fanrong; Tian, Jie

    2014-03-01

    Studies on training/expertise-related effects on human brain in context of neuroplasticity have revealed that plastic changes modulate not only task activations but also patterns and strength of internetworks and intranetworks functional connectivity in the resting state. Much has known about plastic changes in resting state on global level; however, how training/expertise-related effect affects patterns of local spontaneous activity in resting brain remains elusive. We investigated the homogeneity of local blood oxygen level-dependent fluctuations in the resting state using a regional homogeneity (ReHo) analysis among 16 acupuncturists and 16 matched nonacupuncturists (NA). To prove acupuncturists' expertise, we used a series of psychophysical tests. Our results demonstrated that, acupuncturists significantly outperformed NA in tactile-motor and emotional regulation domain and the acupuncturist group showed increased coherence in local BOLD signal fluctuations in the left primary motor cortex (MI), the left primary somatosensory cortex (SI) and the left ventral medial prefrontal cortex/orbitofrontal cortex (VMPFC/OFC). Regression analysis displayed that, in the acupuncturists group, ReHo of VMPFC/OFC could predict behavioral outcomes, evidenced by negative correlation between unpleasantness ratings and ReHo of VMPFC/OFC and ReHo of SI and MI positively correlated with the duration of acupuncture practice. We suggest that expertise could modulate patterns of local resting state activity by increasing regional clustering strength, which is likely to contribute to advanced local information processing efficiency. Our study completes the understanding of neuroplasticity changes by adding the evidence of local resting state activity alterations, which is helpful for elucidating in what manner training effect extends beyond resting state.

  17. 33 CFR 137.15 - References: Where can I get a copy of the publication mentioned in this part?

    Science.gov (United States)

    2010-07-01

    ...-OWNER DEFENSE Introduction § 137.15 References: Where can I get a copy of the publication mentioned in... inspection at the Coast Guard National Pollution Funds Center, Law Library, 4200 Wilson Boulevard, Suite 1000...

  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. Effects of different endocrine disruptor (EDC) mixtures on gene expression in neonatal rat brain regions

    DEFF Research Database (Denmark)

    Lichtensteiger, Walter; Bassetti-Gaille, Catherine; Faass, Oliver

    2013-01-01

    EDC mixtures on gene expression in developing brain. Amix (8 anti-androgenic chemicals), Emix (4 estrogenic chemicals) and Tmix (Amix + Emix + paracetamol recently identified as anti-androgenic) were administered by oral gavage to rat dams from gestational day 7 until weaning, at doses corresponding...... to 450×, 200× and 100× high end human intakes (S. Christiansen et al., 2012. International Journal of Andrology 35, 303). At postnatal day 6, during the last part of sexual brain differentiation, exon microarray analyses were performed in medial preoptic area (MPO) in the highest dose group, and real...... of individual mRNAs demonstrated treatment- and sex-dependent differences between MPO and VMH. Effects were dose-dependent. Prominent are effects on the expression of genes involved in excitatory glutamatergic synapse formation and function. These data indicate that effects of complex EDC mixtures on developing...

  1. FAUNISTICAL DATA REGARDING SPIDERS (ARACHNIDA: ARANEAE FROM SOUTH-EASTERN ROMANIA WITH MENTION OF SOME RARE SPECIES

    Directory of Open Access Journals (Sweden)

    I. DUMA

    2005-01-01

    Full Text Available In this paper we present the results of the faunistical study made in the south-eastern Romania in the summers of 2004 and 2006. We found 118 species of araneae belonging to 21 families. Among them there were some rare species: Argiope lobata (Pallas, 1772 mentioned for the third time in Romania, Hariaeus melloteei (Simon, 1886 mentioned for the second time in our country and Latrodectus tredecimguttatus (Rossi, 1890.

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

    OpenAIRE

    Mackey, Scott,; Chaarani, Bader; Kan, Kees-Jan; Philip A. Spechler; Orr, Catherine; Banaschewski, Tobias; Barker, Gareth; Arun L W Bokde; Bromberg, Uli; Büchel, Christian; Cattrell, Anna; Conrod, Patricia J.; Desrivières, Sylvane; Flor, Herta; Frouin, Vincent

    2016-01-01

    IN_PRESS Export Date: 27 September 2016 Article in Press Background Individual differences in impulsivity and early adversity are known to be strong predictors of adolescent antisocial behavior. However, the neurobiological bases of impulsivity and their relation to antisocial behavior and adversity are poorly understood. Methods Impulsivity was estimated with a temporal discounting task. Voxel-based morphometry was used to determine the brain structural correlates of tempora...

  3. The effects of aerobic exercise on the structure and function of DMN-related brain regions: a systematic review.

    Science.gov (United States)

    Li, Mo-Yi; Huang, Mao-Mao; Li, Shu-Zhen; Tao, Jing; Zheng, Guo-Hua; Chen, Li-Dian

    2016-08-05

    Physical activity may play a role in both the prevention and slowing of brain volume loss and may be beneficial in terms of improving the functional connectivity of brain regions. But much less is known about the potential benefit of aerobic exercise for the structure and function of the default mode network (DMN) brain regions. This systematic review examines the effects of aerobic exercise on the structure and function of DMN brain regions in human adulthood. Seven electronic databases were searched for prospective controlled studies published up to April 2015. The quality of the selected studies was evaluated with the Cochrane Collaboration's tool for assessing the risk of bias. RevMan 5.3 software was applied for data analysis. Finally, 14 studies with 631 participants were identified. Meta-analysis revealed that aerobic exercise could significantly increase right hippocampal volume (SMD = 0.26, 95% CI 0.01-0.51, p = 0.04, I(2) = 7%, 4 studies), and trends of similar effects were observed in the total (SMD = 0.12, 95% CI -0.17 to 0.41, p = 0.43, I(2) = 0%, 5 studies), left (SMD = 0.12, 95% CI -0.13 to 0.37, p = 0.33, I(2) = 14%, 4 studies), left anterior (SMD = 0.12, 95% CI -0.16 to 0.40, p = 0.41, I(2) = 74%, 2 studies) and right anterior (SMD = 0.10, 95% CI -0.17 to 0.38, p = 0.46, I(2) = 76%, 4 studies) hippocampal volumes compared to the no-exercise interventions. A few studies reported that relative to no-exercise interventions, aerobic exercise could significantly decrease the atrophy of the medial temporal lobe, slow the anterior cingulate cortex (ACC) volume loss, increase functional connectivity within the hippocampus and improve signal activation in the cingulate gyrus and ACC. The current review suggests that aerobic exercise may have positive effects on the right hippocampus and potentially beneficial effects on the overall and other parts of the hippocampus, the cingulate cortex and the medial temporal areas of the DMN. Moreover, aerobic exercise

  4. Regional brain volume abnormalities in Lesch-Nyhan disease and its variants: a cross-sectional study.

    Science.gov (United States)

    Schretlen, David J; Varvaris, Mark; Ho, Tiffany E; Vannorsdall, Tracy D; Gordon, Barry; Harris, James C; Jinnah, H A

    2013-12-01

    Lesch-Nyhan disease is a rare, X-linked, neurodevelopmental metabolic disorder that is caused by abnormalities in the levels of hypoxanthine-guanine phosphoribosyltransferase enzyme activity. The neural substrates associated with Lesch-Nyhan disease remain poorly understood. We aimed to use voxel-based morphometry to identify affected brain regions in classic Lesch-Nyhan disease and Lesch-Nyhan variant disease, and to identify regions that differ between the two disease types. In this cross-sectional study, we recruited patients with classic Lesch-Nyhan disease or Lesch-Nyhan variant disease from clinics, referrals, the Lesch-Nyhan Syndrome Registry, and the Matheny School and Hospital (Peapack, NJ, USA), and healthy controls from the Baltimore metropolitan area (MD, USA). We used voxel-based morphometry to analyse grey matter volume between groups using a three-group ANCOVA, followed by six pairwise post-hoc group comparisons. Between Oct 3, 1993, and April 29, 2013, we recruited 21 patients with classic Lesch-Nyhan disease, 17 patients with variant disease, and 33 healthy controls. Patients with classic Lesch-Nyhan disease had a 20% reduction in intracranial volume (17% reduction in grey matter volume; 26% reduction in white matter volume) compared with healthy adults. The largest differences were in basal ganglia, and frontotemporal and limbic regions, with sparing of parieto-occipital regions. Grey matter volumes of patients with Lesch-Nyhan variant disease were invariably between those of patients with classic Lesch-Nyhan disease and healthy controls. Compared with healthy controls, patients with classic disease showed additional grey matter volume reductions in the temporal lobe and left lateralised structures, and patients with variant disease showed additional reductions in lingual and precuneus regions with sparing of right frontal and temporal regions. Patients with classic disease had reductions of volume in the ventral striatum and prefrontal areas

  5. Extended exposure to a palatable cafeteria diet alters gene expression in brain regions implicated in reward, and withdrawal from this diet alters gene expression in brain regions associated with stress.

    Science.gov (United States)

    Martire, Sarah I; Maniam, Jayanthi; South, Timothy; Holmes, Nathan; Westbrook, R Fred; Morris, Margaret J

    2014-05-15

    Like people, rodents exposed to energy-rich foods over-eat and become overweight. Removal of this diet activates stress systems, which may explain why people have difficulty dieting. We exposed rats to energy-rich foods in order to identify changes in the brain induced by that diet and by its removal. Sprague Dawley rats were fed lab-chow or an energy-rich cafeteria diet (plus chow). Following 6 or 15 weeks, half of each group was switched to the opposing diet. Rats were culled 48-h later. We measured fat mass, plasma hormones, and assessed brains for mRNA expression of several genes. Cafeteria-fed rats consumed more kilojoules, weighed more and had elevated leptin (plus reduced CORT at 15 weeks) relative to chow-fed rats. Fifteen weeks of cafeteria diet suppressed μ-opioid and CB1 receptor mRNA in the VTA, but elevated amygdala GR, and 6 weeks of cafeteria diet reduced BDNF, compared to chow-fed rats. Rats switched to the cafeteria diet ate similar amounts as rats maintained on the diet, and switching to cafeteria diet after 15 weeks reduced amygdala GR expression. Rats switched to chow ate less than rats maintained on chow, and switching to chow following 15 weeks of cafeteria diet increased hypothalamic CRH mRNA. Therefore, 15 weeks of cafeteria diet produced changes in brain regions implicated in reward processes. Switching these rats to chow activated the HPA axis, while switching chow-fed rats to the cafeteria diet decreased GR expression in the amygdala, a region associated with stress. These findings have implications for dieting in humans. Crown Copyright © 2014. Published by Elsevier B.V. All rights reserved.

  6. TMS-EEG: A window into the neurophysiological effects of transcranial electrical stimulation in non-motor brain regions.

    Science.gov (United States)

    Hill, Aron T; Rogasch, Nigel C; Fitzgerald, Paul B; Hoy, Kate E

    2016-05-01

    Transcranial electrical stimulation (tES) techniques are able to induce changes in cortical excitability and plasticity through the administration of weak currents to the brain and are currently being used to manipulate a vast array of cognitive processes. Despite the widespread use of tES technologies within both research and remedial settings, their precise neurophysiological mechanisms of action are not well established outside of the motor cortex. The expanding use of tES within non-motor brain regions highlights the growing need for a more comprehensive understanding of the effects of stimulation across a diversity of cortical locations. The combination of transcranial magnetic stimulation with electroencephalography (TMS-EEG) provides a method of directly probing both local and widespread changes in brain neurophysiology, through the recording of TMS-evoked potentials and cortical oscillations. In this review we explore TMS-EEG as a tool for examining the impact of tES on cortical function and argue that multimodal approaches which combine tES with TMS-EEG could lead to a deeper understanding of the mechanisms which underlie tES-induced cognitive modulation.

  7. Brain Regions for Perceiving and Reasoning about Other People in School-Aged Children

    Science.gov (United States)

    Saxe, Rebecca R.; Whitfield-Gabrieli, Susan; Scholz, Jonathan; Pelphrey, Kevin A.

    2009-01-01

    Neuroimaging studies with adults have identified cortical regions recruited when people think about other people's thoughts (theory of mind): temporo-parietal junction, posterior cingulate, and medial prefrontal cortex. These same regions were recruited in 13 children aged 6-11 years when they listened to sections of a story describing a…

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

    DEFF Research Database (Denmark)

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

    1982-01-01

    Regional cerebral blood flow (rCBF) was measured in 23 patients with brain tumors using the 133Xe intra-carotid injection method and a 254 channel gamma camera. The glioblastomas (4) and astrocytomas (4) all showed hyperemia in the tumor and tumor-near region. This was also seen in several mening...

  9. Regional variation in brain white matter diffusion index changes following chemoradiotherapy: a prospective study using tract-based spatial statistics.

    Directory of Open Access Journals (Sweden)

    Christopher H Chapman

    Full Text Available There is little known about how brain white matter structures differ in their response to radiation, which may have implications for radiation-induced neurocognitive impairment. We used diffusion tensor imaging (DTI to examine regional variation in white matter changes following chemoradiotherapy.Fourteen patients receiving two or three weeks of whole-brain radiation therapy (RT ± chemotherapy underwent DTI pre-RT, at end-RT, and one month post-RT. Three diffusion indices were measured: fractional anisotropy (FA, radial diffusivity (RD, and axial diffusivity (AD. We determined significant individual voxel changes of diffusion indices using tract-based spatial statistics, and mean changes of the indices within fourteen white matter structures of interest.Voxels of significant FA decreases and RD increases were seen in all structures (p<0.05, with the largest changes (20-50% in the fornix, cingula, and corpus callosum. There were highly significant between-structure differences in pre-RT to end-RT mean FA changes (p<0.001. The inferior cingula had a mean FA decrease from pre-RT to end-RT significantly greater than 11 of the 13 other structures (p<0.00385.Brain white matter structures varied greatly in their response to chemoradiotherapy as measured by DTI changes. Changes in FA and RD related to white matter demyelination were prominent in the cingula and fornix, structures relevant to radiation-induced neurocognitive impairment. Future research should evaluate DTI as a predictive biomarker of brain chemoradiotherapy adverse effects.

  10. B7-H1 shapes T-cell–mediated brain endothelial cell dysfunction and regional encephalitogenicity in spontaneous CNS autoimmunity

    Science.gov (United States)

    Klotz, Luisa; Kuzmanov, Ivan; Hucke, Stephanie; Gross, Catharina C.; Posevitz, Vilmos; Dreykluft, Angela; Schulte-Mecklenbeck, Andreas; Janoschka, Claudia; Lindner, Maren; Herold, Martin; Schwab, Nicholas; Ludwig-Portugall, Isis; Kurts, Christian; Meuth, Sven G.; Kuhlmann, Tanja; Wiendl, Heinz

    2016-01-01

    Molecular mechanisms that determine lesion localization or phenotype variation in multiple sclerosis are mostly unidentified. Although transmigration of activated encephalitogenic T cells across the blood–brain barrier (BBB) is a crucial step in the disease pathogenesis of CNS autoimmunity, the consequences on brain endothelial barrier integrity upon interaction with such T cells and subsequent lesion formation and distribution are largely unknown. We made use of a transgenic spontaneous mouse model of CNS autoimmunity characterized by inflammatory demyelinating lesions confined to optic nerves and spinal cord (OSE mice). Genetic ablation of a single immune-regulatory molecule in this model [i.e., B7-homolog 1 (B7-H1, PD-L1)] not only significantly increased incidence of spontaneous CNS autoimmunity and aggravated disease course, especially in the later stages of disease, but also importantly resulted in encephalitogenic T-cell infiltration and lesion formation in normally unaffected brain regions, such as the cerebrum and cerebellum. Interestingly, B7-H1 ablation on myelin oligodendrocyte glycoprotein-specific CD4+ T cells, but not on antigen-presenting cells, amplified T-cell effector functions, such as IFN-γ and granzyme B production. Therefore, these T cells were rendered more capable of eliciting cell contact-dependent brain endothelial cell dysfunction and increased barrier permeability in an in vitro model of the BBB. Our findings suggest that a single immune-regulatory molecule on T cells can be ultimately responsible for localized BBB breakdown, and thus substantial changes in lesion topography in the context of CNS autoimmunity. PMID:27671636

  11. Waxholm Space atlas of the rat brain hippocampal region: three-dimensional delineations based on magnetic resonance and diffusion tensor imaging.

    Science.gov (United States)

    Kjonigsen, Lisa J; Lillehaug, Sveinung; Bjaalie, Jan G; Witter, Menno P; Leergaard, Trygve B

    2015-03-01

    Atlases of the rat brain are widely used as reference for orientation, planning of experiments, and as tools for assigning location to experimental data. Improved quality and use of magnetic resonance imaging (MRI) and other tomographical imaging techniques in rats have allowed the development of new three-dimensional (3-D) volumetric brain atlas templates. The rat hippocampal region is a commonly used model for basic research on memory and learning, and for preclinical investigations of brain disease. The region features a complex anatomical organization with multiple subdivisions that can be identified on the basis of specific cytoarchitectonic or chemoarchitectonic criteria. We here investigate the extent to which it is possible to identify boundaries of divisions of the hippocampal region on the basis of high-resolution MRI contrast. We present the boundaries of 13 divisions, identified and delineated based on multiple types of image contrast observed in the recently published Waxholm Space MRI/DTI template for the Sprague Dawley rat brain (Papp et al., Neuroimage 97:374-386, 2014). The new detailed delineations of the hippocampal formation and parahippocampal region (Waxholm Space atlas of the Sprague Dawley rat brain, v2.0) are shared via the INCF Software Center (http://software.incf.org/), where also the MRI/DTI reference template is available. The present update of the Waxholm Space atlas of the rat brain is intended to facilitate interpretation, analysis, and integration of experimental data from this anatomically complex region.

  12. Iron-Restricted Diet Affects Brain Ferritin Levels, Dopamine Metabolism and Cellular Prion Protein in a Region-Specific Manner

    Directory of Open Access Journals (Sweden)

    Jessica M. V. Pino

    2017-05-01

    Full Text Available Iron is an essential micronutrient for several physiological functions, including the regulation of dopaminergic neurotransmission. On the other hand, both iron, and dopamine can affect the folding and aggregation of proteins related with neurodegenerative diseases, such as cellular prion protein (PrPC and α-synuclein, suggesting that deregulation of iron homeostasis and the consequential disturbance of dopamine metabolism can be a risk factor for conformational diseases. These proteins, in turn, are known to participate in the regulation of iron and dopamine metabolism. In this study, we evaluated the effects of dietary iron restriction on brain ferritin levels, dopamine metabolism, and the expression levels of PrPC and α-synuclein. To achieve this goal, C57BL/6 mice were fed with iron restricted diet (IR or with normal diet (CTL for 1 month. IR reduced iron and ferritin levels in liver. Ferritin reduction was also observed in the hippocampus. However, in the striatum of IR group, ferritin level was increased, suggesting that under iron-deficient condition, each brain area might acquire distinct capacity to store iron. Increased lipid peroxidation was observed only in hippocampus of IR group, where ferritin level was reduced. IR also generated discrete results regarding dopamine metabolism of distinct brain regions: in striatum, the level of dopamine metabolites (DOPAC and HVA was reduced; in prefrontal cortex, only HVA was increased along with the enhanced MAO-A activity; in hippocampus, no alterations were observed. PrPC levels were increased only in the striatum of IR group, where ferritin level was also increased. PrPC is known to play roles in iron uptake. Thus, the increase of PrPC in striatum of IR group might be related to the increased ferritin level. α-synuclein was not altered in any regions. Abnormal accumulation of ferritin, increased MAO-A activity or lipid peroxidation are molecular features observed in several neurological

  13. Regional brain stem atrophy in idiopathic Parkinson's disease detected by anatomical MRI.

    Science.gov (United States)

    Jubault, Thomas; Brambati, Simona M; Degroot, Clotilde; Kullmann, Benoît; Strafella, Antonio P; Lafontaine, Anne-Louise; Chouinard, Sylvain; Monchi, Oury

    2009-12-10

    Idiopathic Parkinson's disease (PD) is a neurodegenerative disorder characterized by the dysfunction of dopaminergic dependent cortico-basal ganglia loops and diagnosed on the basis of motor symptoms (tremors and/or rigidity and bradykinesia). Post-mortem studies tend to show that the destruction of dopaminergic neurons in the substantia nigra constitutes an intermediate step in a broader neurodegenerative process rather than a unique feature of Parkinson's disease, as a consistent pattern of progression would exist, originating from the medulla oblongata/pontine tegmentum. To date, neuroimaging techniques have been unable to characterize the pre-symptomatic stages of PD. However, if such a regular neurodegenerative pattern were to exist, consistent damages would be found in the brain stem, even at early stages of the disease. We recruited 23 PD patients at Hoenn and Yahr stages I to II of the disease and 18 healthy controls (HC) matched for age. T1-weighted anatomical scans were acquired (MPRAGE, 1 mm3 resolution) and analyzed using an optimized VBM protocol to detect white and grey matter volume reduction without spatial a priori. When the HC group was compared to the PD group, a single cluster exhibited statistical difference (p<0.05 corrected for false detection rate, 4287 mm3) in the brain stem, between the pons and the medulla oblongata. The present study provides in-vivo evidence that brain stem damage may be the first identifiable stage of PD neuropathology, and that the identification of this consistent damage along with other factors could help with earlier diagnosis in the future. This damage could also explain some non-motor symptoms in PD that often precede diagnosis, such as autonomic dysfunction and sleep disorders.

  14. Regional brain stem atrophy in idiopathic Parkinson's disease detected by anatomical MRI.

    Directory of Open Access Journals (Sweden)

    Thomas Jubault

    Full Text Available Idiopathic Parkinson's disease (PD is a neurodegenerative disorder characterized by the dysfunction of dopaminergic dependent cortico-basal ganglia loops and diagnosed on the basis of motor symptoms (tremors and/or rigidity and bradykinesia. Post-mortem studies tend to show that the destruction of dopaminergic neurons in the substantia nigra constitutes an intermediate step in a broader neurodegenerative process rather than a unique feature of Parkinson's disease, as a consistent pattern of progression would exist, originating from the medulla oblongata/pontine tegmentum. To date, neuroimaging techniques have been unable to characterize the pre-symptomatic stages of PD. However, if such a regular neurodegenerative pattern were to exist, consistent damages would be found in the brain stem, even at early stages of the disease. We recruited 23 PD patients at Hoenn and Yahr stages I to II of the disease and 18 healthy controls (HC matched for age. T1-weighted anatomical scans were acquired (MPRAGE, 1 mm3 resolution and analyzed using an optimized VBM protocol to detect white and grey matter volume reduction without spatial a priori. When the HC group was compared to the PD group, a single cluster exhibited statistical difference (p<0.05 corrected for false detection rate, 4287 mm3 in the brain stem, between the pons and the medulla oblongata. The present study provides in-vivo evidence that brain stem damage may be the first identifiable stage of PD neuropathology, and that the identification of this consistent damage along with other factors could help with earlier diagnosis in the future. This damage could also explain some non-motor symptoms in PD that often precede diagnosis, such as autonomic dysfunction and sleep disorders.

  15. A comparative antibody analysis of Pannexin1 expression in four rat brain regions reveals varying subcellular localizations

    Directory of Open Access Journals (Sweden)

    Angela C Cone

    2013-02-01

    Full Text Available 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 patterns. Localizations of Panx1 in brain slices were generated using automated wide-field mosaic confocal microscopy for imaging large regions of interest while retaining maximum resolution for examining cell populations and compartments. We compared Panx1 expression over the cerebellum, hippocampus with adjacent cortex, thalamus and olfactory bulb. While Panx1 localizes to the same neuronal cell types, subcellular localizations differ. Two antibodies with epitopes against the intracellular loop and one against the carboxy terminus preferentially labeled cell bodies, while an antibody raised against an N-terminal peptide highlighted neuronal processes more than cell bodies. These labeling patterns may be a reflection of different cellular and subcellular localizations of full-length and/or modified Panx1 channels where each antibody is highlighting unique or differentially accessible Panx1 populations. However, we cannot rule out that one or more of these antibodies have specificity issues. All data associated with experiments from these four antibodies are presented in a manner that allows them to be compared and our claims thoroughly evaluated, rather than eliminating results that were questionable. Each antibody is given a unique identifier through the NIF Antibody Registry that can be used to track usage of individual antibodies across papers and all image and metadata are made available in the public repository, the Cell Centered Database, for on

  16. 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.

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

    Science.gov (United States)

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

    2012-01-01

    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 patterns. Localizations of Panx1 in brain slices were generated using automated wide field mosaic confocal