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Sample records for human postmortem brain

  1. Isolation of primary microglia from the human post-mortem brain: effects of ante- and post-mortem variables.

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    Mizee, Mark R; Miedema, Suzanne S M; van der Poel, Marlijn; Adelia; Schuurman, Karianne G; van Strien, Miriam E; Melief, Jeroen; Smolders, Joost; Hendrickx, Debbie A; Heutinck, Kirstin M; Hamann, Jörg; Huitinga, Inge

    2017-02-17

    Microglia are key players in the central nervous system in health and disease. Much pioneering research on microglia function has been carried out in vivo with the use of genetic animal models. However, to fully understand the role of microglia in neurological and psychiatric disorders, it is crucial to study primary human microglia from brain donors. We have developed a rapid procedure for the isolation of pure human microglia from autopsy tissue using density gradient centrifugation followed by CD11b-specific cell selection. The protocol can be completed in 4 h, with an average yield of 450,000 and 145,000 viable cells per gram of white and grey matter tissue respectively. This method allows for the immediate phenotyping of microglia in relation to brain donor clinical variables, and shows the microglia population to be distinguishable from autologous choroid plexus macrophages. This protocol has been applied to samples from over 100 brain donors from the Netherlands Brain Bank, providing a robust dataset to analyze the effects of age, post-mortem delay, brain acidity, and neurological diagnosis on microglia yield and phenotype. Our data show that cerebrospinal fluid pH is positively correlated to microglial cell yield, but donor age and post-mortem delay do not negatively affect viable microglia yield. Analysis of CD45 and CD11b expression showed that changes in microglia phenotype can be attributed to a neurological diagnosis, and are not influenced by variation in ante- and post-mortem parameters. Cryogenic storage of primary microglia was shown to be possible, albeit with variable levels of recovery and effects on phenotype and RNA quality. Microglial gene expression substantially changed due to culture, including the loss of the microglia-specific markers, showing the importance of immediate microglia phenotyping. We conclude that primary microglia can be isolated effectively and rapidly from human post-mortem brain tissue, allowing for the study of the

  2. Limited predictability of postmortem human brain tissue quality by RNA integrity numbers.

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    Sonntag, Kai-C; Tejada, George; Subburaju, Sivan; Berretta, Sabina; Benes, Francine M; Woo, Tsung-Ung W

    2016-07-01

    The RNA integrity number (RIN) is often considered to be a critical measure of the quality of postmortem human brains. However, it has been suggested that RINs do not necessarily reflect the availability of intact mRNA. Using the Agilent bioanalyzer and qRT-PCR, we explored whether RINs provide a meaningful way of assessing mRNA degradation and integrity in human brain samples by evaluating the expression of 3'-5' mRNA sequences of the cytochrome C-1 (CYC1) gene. Analysis of electropherograms showed that RINs were not consistently correlated with RNA or cDNA profiles and appeared to be poor predictors of overall cDNA quality. Cycle thresholds from qRT-PCR analysis to quantify the amount of CYC1 mRNA revealed positive correlations of RINs with amplification of full-length transcripts, despite the variable degree of linear degradation along the 3'-5' sequence. These data demonstrate that in postmortem human brain tissue the RIN is an indicator of mRNA quantity independent of degradation, but does not predict mRNA integrity, suggesting that RINs provide an incomplete measure of brain tissue quality. Quality assessment of postmortem human brains by RNA integrity numbers (RINs) may be misleading, as they do not measure intact mRNAs. We show that the RIN is an indicator of mRNA quantity independent of degradation, but does not predict mRNA integrity, suggesting that RINs provide an incomplete measure of brain tissue quality. Our results resolve controversial assumption on interpreting quality assessments of human postmortem brains by RINs. © 2016 International Society for Neurochemistry.

  3. Autoradiographic analysis of alpha 1-noradrenergic receptors in the human brain postmortem. Effect of suicide

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    Gross-Isseroff, R.; Dillon, K.A.; Fieldust, S.J.; Biegon, A. (Weizmann Institute of Science, Rehovot (Israel))

    1990-11-01

    In vitro quantitative autoradiography of alpha 1-noradrenergic receptors, using tritiated prazosin as a ligand, was performed on 24 human brains postmortem. Twelve brains were obtained from suicide victims and 12 from matched controls. We found significant lower binding to alpha 1 receptors in several brain regions of the suicide group as compared with matched controls. This decrease in receptor density was evident in portions of the prefrontal cortex, as well as the temporal cortex and in the caudate nucleus. Age, sex, presence of alcohol, and time of death to autopsy did not affect prazosin binding, in our sample, as measured by autoradiography.

  4. Postmortem diffusion MRI of the human brainstem and thalamus for deep brain stimulator electrode localization.

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    Calabrese, Evan; Hickey, Patrick; Hulette, Christine; Zhang, Jingxian; Parente, Beth; Lad, Shivanand P; Johnson, G Allan

    2015-08-01

    Deep brain stimulation (DBS) is an established surgical therapy for medically refractory tremor disorders including essential tremor (ET) and is currently under investigation for use in a variety of other neurologic and psychiatric disorders. There is growing evidence that the anti-tremor effects of DBS for ET are directly related to modulation of the dentatorubrothalamic tract (DRT), a white matter pathway that connects the cerebellum, red nucleus, and ventral intermediate nucleus of the thalamus. Emerging white matter targets for DBS, like the DRT, will require improved three-dimensional (3D) reference maps of deep brain anatomy and structural connectivity for accurate electrode targeting. High-resolution diffusion MRI of postmortem brain specimens can provide detailed volumetric images of important deep brain nuclei and 3D reconstructions of white matter pathways with probabilistic tractography techniques. We present a high spatial and angular resolution diffusion MRI template of the postmortem human brainstem and thalamus with 3D reconstructions of the nuclei and white matter tracts involved in ET circuitry. We demonstrate registration of these data to in vivo, clinical images from patients receiving DBS therapy, and correlate electrode proximity to tractography of the DRT with improvement of ET symptoms. © 2015 Wiley Periodicals, Inc.

  5. The post-synaptic density of human postmortem brain tissues: an experimental study paradigm for neuropsychiatric illnesses.

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    Chang-Gyu Hahn

    Full Text Available Recent molecular genetics studies have suggested various trans-synaptic processes for pathophysiologic mechanisms of neuropsychiatric illnesses. Examination of pre- and post-synaptic scaffolds in the brains of patients would greatly aid further investigation, yet such an approach in human postmortem tissue has yet to be tested. We have examined three methods using density gradient based purification of synaptosomes followed by detergent extraction (Method 1 and the pH based differential extraction of synaptic membranes (Methods 2 and 3. All three methods separated fractions from human postmortem brains that were highly enriched in typical PSD proteins, almost to the exclusion of pre-synaptic proteins. We examined these fractions using electron microscopy (EM and verified the integrity of the synaptic membrane and PSD fractions derived from human postmortem brain tissues. We analyzed protein composition of the PSD fractions using two dimensional liquid chromatography tandem mass spectrometry (2D LC-MS/MS and observed known PSD proteins by mass spectrometry. Immunoprecipitation and immunoblot studies revealed that expected protein-protein interactions and certain posttranscriptional modulations were maintained in PSD fractions. Our results demonstrate that PSD fractions can be isolated from human postmortem brain tissues with a reasonable degree of integrity. This approach may foster novel postmortem brain research paradigms in which the stoichiometry and protein composition of specific microdomains are examined.

  6. Selection of Candidate Housekeeping Genes for Normalization in Human Postmortem Brain Samples

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    Aldo Pagano

    2011-08-01

    Full Text Available The most frequently used technique to study the expression profile of genes involved in common neurological disorders is quantitative real-time RT-PCR, which allows the indirect detection of very low amounts of selected mRNAs in tissue samples. Expression analysis by RT-qPCR requires an appropriate normalization to the expression level of genes characterized by a stable, constitutive transcription. However, the identification of a gene transcribed at a very stable level is difficult if not impossible, since significant fluctuations of the level of mRNA synthesis often accompanies changes of cell behavior. The aim of this study is to identify the most stable genes in postmortem human brain samples of patients affected by Alzheimer’s disease (AD suitable as reference genes. The experiments analyzed 12 commonly used reference genes in brain samples from eight individuals with AD and seven controls. After a careful analysis of the results calculated by geNorm and NormFinder algorithms, we found that CYC1 and EIF4A2 are the best reference genes. We remark on the importance of the determination of the best reference genes for each sample to be analyzed and suggest a practical combination of reference genes to be used in the analysis of human postmortem samples.

  7. Open chromatin profiling of human postmortem brain infers functional roles for non-coding schizophrenia loci.

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    Fullard, John F; Giambartolomei, Claudia; Hauberg, Mads E; Xu, Ke; Voloudakis, Georgios; Shao, Zhiping; Bare, Christopher; Dudley, Joel T; Mattheisen, Manuel; Robakis, Nikolaos K; Haroutunian, Vahram; Roussos, Panos

    2017-05-15

    Open chromatin provides access to DNA-binding proteins for the correct spatiotemporal regulation of gene expression. Mapping chromatin accessibility has been widely used to identify the location of cis regulatory elements (CREs) including promoters and enhancers. CREs show tissue- and cell-type specificity and disease-associated variants are often enriched for CREs in the tissues and cells that pertain to a given disease. To better understand the role of CREs in neuropsychiatric disorders we applied the Assay for Transposase Accessible Chromatin followed by sequencing (ATAC-seq) to neuronal and non-neuronal nuclei isolated from frozen postmortem human brain by fluorescence-activated nuclear sorting (FANS). Most of the identified open chromatin regions (OCRs) are differentially accessible between neurons and non-neurons, and show enrichment with known cell type markers, promoters and enhancers. Relative to those of non-neurons, neuronal OCRs are more evolutionarily conserved and are enriched in distal regulatory elements. Transcription factor (TF) footprinting analysis identifies differences in the regulome between neuronal and non-neuronal cells and ascribes putative functional roles to a number of non-coding schizophrenia (SCZ) risk variants. Among the identified variants is a Single Nucleotide Polymorphism (SNP) proximal to the gene encoding SNX19. In vitro experiments reveal that this SNP leads to an increase in transcriptional activity. As elevated expression of SNX19 has been associated with SCZ, our data provide evidence that the identified SNP contributes to disease. These results represent the first analysis of OCRs and TF-binding sites in distinct populations of postmortem human brain cells and further our understanding of the regulome and the impact of neuropsychiatric disease-associated genetic risk variants. © The Author 2017. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

  8. Novel microRNA discovery using small RNA sequencing in post-mortem human brain.

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    Wake, Christian; Labadorf, Adam; Dumitriu, Alexandra; Hoss, Andrew G; Bregu, Joli; Albrecht, Kenneth H; DeStefano, Anita L; Myers, Richard H

    2016-10-04

    MicroRNAs (miRNAs) are short, non-coding RNAs that regulate gene expression mainly through translational repression of target mRNA molecules. More than 2700 human miRNAs have been identified and some are known to be associated with disease phenotypes and to display tissue-specific patterns of expression. We used high-throughput small RNA sequencing to discover novel miRNAs in 93 human post-mortem prefrontal cortex samples from individuals with Huntington's disease (n = 28) or Parkinson's disease (n = 29) and controls without neurological impairment (n = 36). A custom miRNA identification analysis pipeline was built, which utilizes miRDeep* miRNA identification and result filtering based on false positive rate estimates. Ninety-nine novel miRNA candidates with a false positive rate of less than 5 % were identified. Thirty-four of the candidate miRNAs show sequence similarity with known mature miRNA sequences and may be novel members of known miRNA families, while the remaining 65 may constitute previously undiscovered families of miRNAs. Nineteen of the 99 candidate miRNAs were replicated using independent, publicly-available human brain RNA-sequencing samples, and seven were experimentally validated using qPCR. We have used small RNA sequencing to identify 99 putative novel miRNAs that are present in human brain samples.

  9. Characterization of CB1 cannabinoid receptor immunoreactivity in postmortem human brain homogenates.

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    De Jesús, M López; Sallés, J; Meana, J J; Callado, L F

    2006-06-30

    The CB1 cannabinoid receptor (CB1) is the predominant type of cannabinoid receptor in the CNS, in which it displays a unique anatomical distribution and is present at higher densities than most other known seven transmembrane domain receptors. Nevertheless, as with almost all seven transmembrane domain receptors, the tertiary and quaternary structure of this receptor is still unknown. Studies of CB1 in rat cerebral tissue are scarce, and even less is known regarding the expression of CB1 in the human brain. Thus, the aim of the present work was to characterize CB1 expression in membranes from postmortem human brain using specific antisera raised against this protein. Western blot analysis of P1 and P2 fractions, and crude plasma membrane preparations from the prefrontal cortex showed that CB1 migrated as a 60 kDa monomer under reducing conditions. These data were confirmed by blotting experiments carried out with human U373MG astrocytoma cells as a positive control for CB1 expression and wild-type CHO cells as negative control. In addition, when proteins were solubilized in the absence of dithiothreitol, the anti-human CB1 antiserum detected a new band migrating at around 120 kDa corresponding in size to a putative CB1 dimer. This band was sensitive to reducing agents (50 mM dithiothreitol) and showed sodium dodecylsulphate stability, suggesting the existence of disulfide-linked CB1 dimers in the membrane preparations. Important differences in the anatomical distribution of CB1 were observed with regard to that described previously in monkey and rat; in the human brain, CB1 levels were higher in cortex and caudate than in the cerebellum.

  10. Differential Changes in Postsynaptic Density Proteins in Postmortem Huntington’s Disease and Parkinson’s Disease Human Brains

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    C. Fourie

    2014-01-01

    Full Text Available NMDA and AMPA-type glutamate receptors and their bound membrane-associated guanylate kinases (MAGUKs are critical for synapse development and plasticity. We hypothesised that these proteins may play a role in the changes in synapse function that occur in Huntington’s disease (HD and Parkinson’s disease (PD. We performed immunohistochemical analysis of human postmortem brain tissue to examine changes in the expression of SAP97, PSD-95, GluA2 and GluN1 in human control, and HD- and PD-affected hippocampus and striatum. Significant increases in SAP97 and PSD-95 were observed in the HD and PD hippocampus, and PSD95 was downregulated in HD striatum. We observed a significant increase in GluN1 in the HD hippocampus and a decrease in GluA2 in HD and PD striatum. Parallel immunohistochemistry experiments in the YAC128 mouse model of HD showed no change in the expression levels of these synaptic proteins. Our human data show that major but different changes occur in glutamatergic proteins in HD versus PD human brains. Moreover, the changes in human HD brains differ from those occurring in the YAC128 HD mouse model, suggesting that unique changes occur at a subcellular level in the HD human hippocampus.

  11. Diffusion tractography of the subcortical auditory system in a postmortem human brain

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    Sitek, Kevin

    2017-01-01

    The subcortical auditory system is challenging to identify with standard human brain imaging techniques: MRI signal decreases toward the center of the brain as well as at higher resolution, both of which are necessary for imaging small brainstem auditory structures.Using high-resolution diffusion-weighted MRI, we asked:Can we identify auditory structures and connections in high-resolution ex vivo images?Which structures and connections can be mapped in vivo?

  12. Gender-specific gene expression in post-mortem human brain: localization to sex chromosomes.

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    Vawter, Marquis P; Evans, Simon; Choudary, Prabhakara; Tomita, Hiroaki; Meador-Woodruff, Jim; Molnar, Margherita; Li, Jun; Lopez, Juan F; Myers, Rick; Cox, David; Watson, Stanley J; Akil, Huda; Jones, Edward G; Bunney, William E

    2004-02-01

    Gender differences in brain development and in the prevalence of neuropsychiatric disorders such as depression have been reported. Gender differences in human brain might be related to patterns of gene expression. Microarray technology is one useful method for investigation of gene expression in brain. We investigated gene expression, cell types, and regional expression patterns of differentially expressed sex chromosome genes in brain. We profiled gene expression in male and female dorsolateral prefrontal cortex, anterior cingulate cortex, and cerebellum using the Affymetrix oligonucleotide microarray platform. Differentially expressed genes between males and females on the Y chromosome (DBY, SMCY, UTY, RPS4Y, and USP9Y) and X chromosome (XIST) were confirmed using real-time PCR measurements. In situ hybridization confirmed the differential expression of gender-specific genes and neuronal expression of XIST, RPS4Y, SMCY, and UTY in three brain regions examined. The XIST gene, which silences gene expression on regions of the X chromosome, is expressed in a subset of neurons. Since a subset of neurons express gender-specific genes, neural subpopulations may exhibit a subtle sexual dimorphism at the level of differences in gene regulation and function. The distinctive pattern of neuronal expression of XIST, RPS4Y, SMCY, and UTY and other sex chromosome genes in neuronal subpopulations may possibly contribute to gender differences in prevalence noted for some neuropsychiatric disorders. Studies of the protein expression of these sex-chromosome-linked genes in brain tissue are required to address the functional consequences of the observed gene expression differences.

  13. An improved anatomical MRI technique with suppression of fixative fluid artifacts for the investigation of human postmortem brain phantoms.

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    Droby, Amgad; Yuen, Kenneth Sung Lai; Schänzer, Anne; Spiwoks-Becker, Isabella; Acker, Till; Lienerth, Bianca; Zipp, Frauke; Deichmann, Ralf

    2017-03-01

    Phantoms are often used to assess MR system stability in multicenter studies. Postmortem brain phantoms best replicate human brain anatomy, allowing for a combined assessment of the MR system and software chain for data analysis. However, a wash-out of fixative fluid affecting T1 values and thus T1-weighted sequences such as magnetization-prepared 180 degrees radiofrequency pulses and rapid gradient-echo (MP-RAGE) has been reported for brain phantoms, hampering their immediate use. The purpose of this study was the creation of anatomical data that provide the characteristics of conventional data while avoiding this artifact. Two brain phantoms were scanned at several time points, acquiring conventional MP-RAGE data and quantitative T1 and proton density (PD) maps. Assuming a suitable cutoff value T1cut , synthetic MP-RAGE data were created from these maps, being T1-weighted for T1 > T1cut to reduce fluid signal in the sulci, but PD-weighted for T1 phantoms, avoiding artifacts induced by the wash-out of fixative fluid, and thus achieving high signal stability shortly after fixation. Magn Reson Med 77:1115-1123, 2017. © 2016 International Society for Magnetic Resonance in Medicine. © 2016 International Society for Magnetic Resonance in Medicine.

  14. A comparison of mitochondrial DNA isolation methods in frozen post-mortem human brain tissue--applications for studies of mitochondrial genetics in brain disorders.

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    Devall, Matthew; Burrage, Joe; Caswell, Richard; Johnson, Matthew; Troakes, Claire; Al-Sarraj, Safa; Jeffries, Aaron R; Mill, Jonathan; Lunnon, Katie

    2015-10-01

    Given that many brain disorders are characterized by mitochondrial dysfunction, there is a growing interest in investigating genetic and epigenetic variation in mitochondrial DNA (mtDNA). One major caveat for such studies is the presence of nuclear-mitochondrial pseudogenes (NUMTs), which are regions of the mitochondrial genome that have been inserted into the nuclear genome over evolution and, if not accounted for, can confound genetic studies of mtDNA. Here we provide the first systematic comparison of methods for isolating mtDNA from frozen post-mortem human brain tissue. Our data show that a commercial method from Miltenyi Biotec, which magnetically isolates mitochondria using antibodies raised against the mitochondrial import receptor subunit TOM22, gives significant mtDNA enrichment and should be considered the method of choice for mtDNA studies in frozen brain tissue.

  15. Experimental Investigation of Cavitation as a Possible Damage Mechanism in Blast-Induced Traumatic Brain Injury in Post-Mortem Human Subject Heads.

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    Salzar, Robert S; Treichler, Derrick; Wardlaw, Andrew; Weiss, Greg; Goeller, Jacques

    2017-04-15

    The potential of blast-induced traumatic brain injury from the mechanism of localized cavitation of the cerebrospinal fluid (CSF) is investigated. While the mechanism and criteria for non-impact blast-induced traumatic brain injury is still unknown, this study demonstrates that local cavitation in the CSF layer of the cranial volume could contribute to these injuries. The cranial contents of three post-mortem human subject (PMHS) heads were replaced with both a normal saline solution and a ballistic gel mixture with a simulated CSF layer. Each were instrumented with multiple pressure transducers and placed inside identical shock tubes at two different research facilities. Sensor data indicates that cavitation may have occurred in the PMHS models at pressure levels below those for a 50% risk of blast lung injury. This study points to skull flexion, the result of the shock wave on the front of the skull leading to a negative pressure in the contrecoup, as a possible mechanism that contributes to the onset of cavitation. Based on observation of intracranial pressure transducer data from the PMHS model, cavitation onset is thought to occur from approximately a 140 kPa head-on incident blast.

  16. Unexpected brain finding in pre-autopsy postmortem CT.

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    Chatzaraki, Vasiliki; Bolliger, Stephan A; Thali, Michael J; Eggert, Sebastian; Ruder, Thomas D

    2017-09-01

    A case is presented in which pre-autopsy postmortem computed tomography (PMCT) revealed an unexpected brain abscess with a related frontal sinusitis and an erosion of the posterior wall of the frontal sinus. PMCT findings enabled the forensic pathologists to adapt protective measures during autopsy and protect their health from infection. Pre-autopsy PMCT has been also useful in the early differential diagnosis procedure. The complementary use of postmortem imaging and autopsy can improve the quality of forensic death investigations.

  17. Distribution patterns of postmortem damage in human mitochondrial DNA

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    Gilbert, M Thomas P; Willerslev, Eske; Hansen, Anders J

    2002-01-01

    The distribution of postmortem damage in mitochondrial DNA retrieved from 37 ancient human DNA samples was analyzed by cloning and was compared with a selection of published animal data. A relative rate of damage (rho(v)) was calculated for nucleotide positions within the human hypervariable region......, such as MT5, have lower in vivo mutation rates and lower postmortem-damage rates. The postmortem data also identify a possible functional subregion of the HVR1, termed "low-diversity 1," through the lack of sequence damage. The amount of postmortem damage observed in mitochondrial coding regions...

  18. Postmortem Quetiapine Reference Concentrations in Brain and Blood

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    Skov, Louise; Johansen, Sys Stybe; Linnet, Kristian

    2015-01-01

    Brain tissue is a useful alternative to blood in postmortem forensic investigations, but scarcity of information on reference concentrations in brain tissue makes interpretation challenging. Here we present a study of 43 cases where the antipsychotic drug quetiapine was quantified in brain tissue...... and related to concentrations in postmortem blood. For cases, where quetiapine was unrelated to the cause of death (N 5 36), the 10–90 percentiles for quetiapine concentrations in brain tissue were 0.030 – 1.54 mg/kg (median 0.48 mg/kg, mean 0.79 mg/kg). Corresponding blood 10 –90 percentile values were 0.......007 – 0.39 mg/kg (median 0.15 mg/kg, mean 0.19 mg/kg), giving brain –blood ratio 10 –90 percentiles of 2.31 – 6.54 (median 3.87, mean 4.32). Both correspond well to the limited amount of data found in the literature. For cases where quetiapine was a contributing factor to death (N 5 5), the median value...

  19. Effect of post-mortem delay on N-terminal huntingtin protein fragments in human control and Huntington disease brain lysates.

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    Schut, Menno H; Patassini, Stefano; Kim, Eric H; Bullock, Jocelyn; Waldvogel, Henry J; Faull, Richard L M; Pepers, Barry A; den Dunnen, Johan T; van Ommen, Gert-Jan B; van Roon-Mom, Willeke M C

    2017-01-01

    Huntington disease is associated with elongation of a CAG repeat in the HTT gene that results in a mutant huntingtin protein. Several studies have implicated N-terminal huntingtin protein fragments in Huntington disease pathogenesis. Ideally, these fragments are studied in human brain tissue. However, the use of human brain tissue comes with certain unavoidable variables such as post mortem delay, artefacts from freeze-thaw cycles and subject-to-subject variation. Knowledge on how these variables might affect N-terminal huntingtin protein fragments in post mortem human brain is important for a proper interpretation of study results. The effect of post mortem delay on protein in human brain is known to vary depending on the protein of interest. In the present study, we have assessed the effect of post mortem delay on N-terminal huntingtin protein fragments using western blot. We mimicked post mortem delay in one individual control case and one individual Huntington disease case with low initial post mortem delay. The influence of subject-to-subject variation on N-terminal huntingtin fragments was assessed in human cortex and human striatum using two cohorts of control and Huntington disease subjects. Our results show that effects of post mortem delay on N-terminal huntingtin protein fragments are minor in our individual subjects. Additionally, one freeze-thaw cycle decreases the huntingtin western blot signal intensity in the cortex control subject, but does not introduce additional N-terminal huntingtin fragments. Our results suggest that subject-to-subject variation contributes more to variability in N-terminal huntingtin fragments than post mortem delay.

  20. Determining the presence of periodontopathic virulence factors in short-term postmortem Alzheimer's disease brain tissue.

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    Poole, Sophie; Singhrao, Sim K; Kesavalu, Lakshmyya; Curtis, Michael A; Crean, StJohn

    2013-01-01

    The aim of this study was to establish a link between periodontal disease and Alzheimer's disease (AD) with a view to identifying the major periodontal disease bacteria (Treponema denticola, Tannerella forsythia, and Porphyromonas gingivalis) and/or bacterial components in brain tissue from 12 h postmortem delay. Our request matched 10 AD cases for tissue from Brains for Dementia Research alongside 10 non-AD age-related controls with similar or greater postmortem interval. We exposed SVGp12, an astrocyte cell line, to culture supernatant containing lipopolysaccharide (LPS) from the putative periodontal bacteria P. gingivalis. The challenged SVGp12 cells and cryosections from AD and control brains were immunolabeled and immunoblotted using a battery of antibodies including the anti-P. gingivalis-specific monoclonal antibody. Immunofluorescence labeling demonstrated the SVGp12 cell line was able to adsorb LPS from culture supernatant on its surface membrane; similar labeling was observed in four out of 10 AD cases. Immunoblotting demonstrated bands corresponding to LPS from P. gingivalis in the SVGp12 cell lysate and in the same four AD brain specimens which were positive when screened by immunofluorescence. All controls remained negative throughout while the same four cases were consistently positive for P. gingivalis LPS (p = 0.029). This study confirms that LPS from periodontal bacteria can access the AD brain during life as labeling in the corresponding controls, with equivalent/longer postmortem interval, was absent. Demonstration of a known chronic oral-pathogen-related virulence factor reaching the human brains suggests an inflammatory role in the existing AD pathology.

  1. The Correlations Between Postmortem Brain Pathologies and Cognitive Dysfunction in Aging and Alzheimer's Disease.

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    Qiu, Wen-Ying; Yang, Qian; Zhang, Wanying; Wang, Naili; Zhang, Di; Huang, Yue; Ma, Chao

    2017-11-06

    Background The pathological diagnostic criteria for Alzheimer's disease (AD) updated by National Institute on Aging-Alzheimer's Association (NIA-AA) in 2012 has been widely adopted, but the clinicopathological relevance remained obscure in Chinese population. Objective This study aims to investigate the correlations between the antemortem clinical cognitive performances and the postmortem neuropathological changes in the aging and AD brains collected in a human brain bank in China. Method A total of 52 human brains with antemortem cognitive status information [Everyday Cognition (ECog)] were collected through the willed donation program by CAMS/PUMC Human Brain Bank. Pathological changes were evaluated with the "ABC" score following the guidelines of NIA-AA. The clinicopathological relationship was analyzed with correlation analysis and general linear multivariate model. Results The general ABC score has a significant correlation with global ECog score (r=0.37, p=0.014) and most of ECog domains. The CERAD score of neuritic plaques (C score) has a significant correlation with global ECog score (r=0.40, p=0.007) and the majority of ECog domains, such as memory (r=0.50, p=0.001), language (r=0.45, p=0.002), visuospatial functions (r=0.31, p=0.040), planning (r=0.35, p=0.021) and organization (r=0.39, p=0.010). The Braak stage of neurofibrillary tangles (NFTs) (B score) has a moderate correlation with memory (r=0.32, p=0.035). The Thal phases of amyloid-β (Aβ) deposits (A score) presents no significant correlation with any of ECog domains. Conclusion In this study, we verified the correlation of postmortem C and B scores, but not the A score with cognition performance in a collection of samples from the Chinese human brain bank. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

  2. Metabolomics of Neurotransmitters and Related Metabolites in Post-Mortem Tissue from the Dorsal and Ventral Striatum of Alcoholic Human Brain.

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    Kashem, Mohammed Abul; Ahmed, Selina; Sultana, Nilufa; Ahmed, Eakhlas U; Pickford, Russell; Rae, Caroline; Šerý, Omar; McGregor, Iain S; Balcar, Vladimir J

    2016-02-01

    We report on changes in neurotransmitter metabolome and protein expression in the striatum of humans exposed to heavy long-term consumption of alcohol. Extracts from post mortem striatal tissue (dorsal striatum; DS comprising caudate nucleus; CN and putamen; P and ventral striatum; VS constituted by nucleus accumbens; NAc) were analysed by high performance liquid chromatography coupled with tandem mass spectrometry. Proteomics was studied in CN by two-dimensional gel electrophoresis followed by mass-spectrometry. Proteomics identified 25 unique molecules expressed differently by the alcohol-affected tissue. Two were dopamine-related proteins and one a GABA-synthesizing enzyme GAD65. Two proteins that are related to apoptosis and/or neuronal loss (BiD and amyloid-β A4 precursor protein-binding family B member 3) were increased. There were no differences in the levels of dopamine (DA), 3,4-dihydrophenylacetic acid (DOPAC), serotonin (5HT), homovanillic acid (HVA), 5-hydroxyindoleacetic acid (HIAA), histamine, L-glutamate (Glu), γ-aminobutyric acid (GABA), tyrosine (Tyr) and tryptophan (Tryp) between the DS (CN and P) and VS (NAc) in control brains. Choline (Ch) and acetylcholine (Ach) were higher and norepinephrine (NE) lower, in the VS. Alcoholic striata had lower levels of neurotransmitters except for Glu (30 % higher in the alcoholic ventral striatum). Ratios of DOPAC/DA and HIAA/5HT were higher in alcoholic striatum indicating an increase in the DA and 5HT turnover. Glutathione was significantly reduced in all three regions of alcohol-affected striatum. We conclude that neurotransmitter systems in both the DS (CN and P) and the VS (NAc) were significantly influenced by long-term heavy alcohol intake associated with alcoholism.

  3. Postmortem concentrations of gamma-hydroxybutyrate (GHB) in peripheral blood and brain tissue - Differentiating between postmortem formation and antemortem intake

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    Thomsen, Ragnar; Rasmussen, Brian Schou; Johansen, Sys Stybe

    2017-01-01

    to fermentation processes. The endogenous nature of GHB leads to difficulty in interpretation of concentrations, as the source of GHB is not obvious. Postmortem brain and blood samples were collected from 221 individuals at autopsy. Of these, 218 were not suspected of having ingested GHB, while GHB intake...... was reported for the last three (cases A-C). Decomposition level was estimated and cases classified into no/minor and advanced decomposition. Brain samples were extracted from the frontal lobe; only gray matter from the cerebral cortex was used. Blood was drawn from the femoral vein. Brain samples were...... homogenized and diluted with water. Brain homogenates or femoral blood were then prepared using protein precipitation and GHB was quantified with UHPLC-MS/MS. For 189 cases where ingestion of GHB was not suspected and where no/minor decomposition had occurred the concentrations were in the range 4.8-45.4mg...

  4. Utility of real-time Taqman PCR for antemortem and postmortem diagnosis of human rabies.

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    Mani, Reeta Subramaniam; Madhusudana, Shampur Narayan; Mahadevan, Anita; Reddy, Vijayalakshmi; Belludi, Ashwin Yajaman; Shankar, Susarla Krishna

    2014-10-01

    Rabies, a fatal zoonotic viral encephalitis remains a neglected disease in India despite a high disease burden. Laboratory confirmation is essential, especially in patients with paralytic rabies who pose a diagnostic dilemma. However, conventional tests for diagnosis of rabies have several limitations. In the present study the utility of a real-time TaqMan PCR assay was evaluated for antemortem/postmortem diagnosis of rabies. Human clinical samples received for antemortem rabies diagnosis (CSF, saliva, nuchal skin biopsy, serum), and samples obtained postmortem from laboratory confirmed rabies in humans (brain tissue, CSF, serum) and animals (brain tissue) were included in the study. All CSF and sera were tested for rabies viral neutralizing antibodies (RVNA) by rapid fluorescent focus inhibition test (RFFIT) and all samples (except sera) were processed for detection of rabies viral RNA by real-time TaqMan PCR. All the 29 (100%) brain tissues from confirmed cases of human and animal rabies, and 11/14 (78.5%) CSF samples obtained postmortem from confirmed human rabies cases were positive by real-time TaqMan PCR. Rabies viral RNA was detected in 5/11 (45.4%) CSF samples, 6/10 (60%) nuchal skin biopsies, and 6/7 (85.7%) saliva samples received for antemortem diagnosis. Real-time TaqMan PCR alone could achieve antemortem rabies diagnosis in 11/13 (84.6%) cases; combined with RVNA detection in CSF antemortem rabies diagnosis could be achieved in all 13 (100%) cases. Real-time TaqMan PCR should be made available widely as an adjunctive test for diagnosis of human rabies in high disease burden countries like India. © 2013 Wiley Periodicals, Inc.

  5. Postmortem Scavenging of Human Remains by Domestic Cats

    Directory of Open Access Journals (Sweden)

    Ananya Suntirukpong, M.D.

    2017-11-01

    Full Text Available Objective: Crime scene investigators, forensic medicine doctors and pathologists, and forensic anthropologists frequently encounter postmortem scavenging of human remains by household pets. Case presentation: The authors present a case report of a partially skeletonized adult male found dead after more than three months in his apartment in Thailand. The body was in an advanced stage of decomposition with nearly complete skeletonization of the head, neck, hands, and feet. The presence of maggots and necrophagous (flesh eating beetles on the body confirmed that insects had consumed much of the soft tissues. Examination of the hand and foot bones revealed canine tooth puncture marks. Evidence of chewing indicated that one or more of the decedent’s three house cats had fed on the body after death. Recognizing and identifying carnivore and rodent activity on the soft flesh and bones of human remains is important in interpreting and reconstructing postmortem damage. Thorough analysis may help explain why skeletal elements are missing, damaged, or out of anatomical position. Conclusion: This report presents a multi-disciplinary approach combining forensic anthropology and forensic medicine in examining and interpreting human remains.

  6. Racking the brain: Detection of cerebral edema on postmortem computed tomography compared with forensic autopsy

    Energy Technology Data Exchange (ETDEWEB)

    Berger, Nicole [Institute of Forensic Medicine, Virtopsy, University of Zurich, Winterthurerstrasse 190/52, 8057 Zurich (Switzerland); Institute of Diagnostic and Interventional Radiology, University Hospital of Zurich, Raemistrasse 100, 8091 Zurich (Switzerland); Ampanozi, Garyfalia; Schweitzer, Wolf; Ross, Steffen G.; Gascho, Dominic [Institute of Forensic Medicine, Virtopsy, University of Zurich, Winterthurerstrasse 190/52, 8057 Zurich (Switzerland); Ruder, Thomas D. [Institute of Forensic Medicine, Virtopsy, University of Zurich, Winterthurerstrasse 190/52, 8057 Zurich (Switzerland); Institute of Diagnostic, Interventional and Pediatric Radiology, University Hospital of Bern, Freiburgstrasse, 3010 Bern (Switzerland); Thali, Michael J. [Institute of Forensic Medicine, Virtopsy, University of Zurich, Winterthurerstrasse 190/52, 8057 Zurich (Switzerland); Flach, Patricia M., E-mail: patricia.flach@irm.uzh.ch [Institute of Forensic Medicine, Virtopsy, University of Zurich, Winterthurerstrasse 190/52, 8057 Zurich (Switzerland); Institute of Diagnostic and Interventional Radiology, University Hospital of Zurich, Raemistrasse 100, 8091 Zurich (Switzerland)

    2015-04-15

    Graphical abstract: -- Highlights: •Postmortem swelling of the brain is a typical finding on PMCT and occurs concomitant with potential antemortem or agonal brain edema. •Cerebral edema despite normal postmortem swelling is indicated by narrowed temporal horns and symmetrical herniation of the cerebral tonsils on PMCT. •Cases with intoxication or asphyxia demonstrated higher deviations of the attenuation between white and gray matter (>20 Hounsfield Units) and a ratio >1.58 between the gray and white matter. •The Hounsfield measurements of the white and gray matter help to determine the cause of death in cases of intoxication or asphyxia. -- Abstract: Purpose: The purpose of this study was to compare postmortem computed tomography with forensic autopsy regarding their diagnostic reliability of differentiating between pre-existing cerebral edema and physiological postmortem brain swelling. Materials and methods: The study collective included a total of 109 cases (n = 109/200, 83 male, 26 female, mean age: 53.2 years) and were retrospectively evaluated for the following parameters (as related to the distinct age groups and causes of death): tonsillar herniation, the width of the outer and inner cerebrospinal fluid spaces and the radiodensity measurements (in Hounsfield Units) of the gray and white matter. The results were compared with the findings of subsequent autopsies as the gold standard for diagnosing cerebral edema. p-Values <0.05 were considered statistically significant. Results: Cerebellar edema (despite normal postmortem swelling) can be reliably assessed using postmortem computed tomography and is indicated by narrowed temporal horns and symmetrical herniation of the cerebellar tonsils (p < 0.001). There was a significant difference (p < 0.001) between intoxication (or asphyxia) and all other causes of death; the former causes demonstrated higher deviations of the attenuation between white and gray matter (>20 Hounsfield Units), and the gray to

  7. Racking the brain: detection of cerebral edema on postmortem computed tomography compared with forensic autopsy.

    Science.gov (United States)

    Berger, Nicole; Ampanozi, Garyfalia; Schweitzer, Wolf; Ross, Steffen G; Gascho, Dominic; Ruder, Thomas D; Thali, Michael J; Flach, Patricia M

    2015-04-01

    The purpose of this study was to compare postmortem computed tomography with forensic autopsy regarding their diagnostic reliability of differentiating between pre-existing cerebral edema and physiological postmortem brain swelling. The study collective included a total of 109 cases (n=109/200, 83 male, 26 female, mean age: 53.2 years) and were retrospectively evaluated for the following parameters (as related to the distinct age groups and causes of death): tonsillar herniation, the width of the outer and inner cerebrospinal fluid spaces and the radiodensity measurements (in Hounsfield Units) of the gray and white matter. The results were compared with the findings of subsequent autopsies as the gold standard for diagnosing cerebral edema. p-Values 20 Hounsfield Units), and the gray to white matter ratio was >1.58 when leukoencephalopathy was excluded. Despite normal postmortem changes, generalized brain edema can be differentiated on postmortem computed tomography, and white and gray matter Hounsfield measurements help to determine the cause of death in cases of intoxication or asphyxia. Racking the brain about feasible applications for a precise and reliable brain diagnostic forensic radiology method has just begun. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

  8. A Genotype Resource for Postmortem Brain Samples from the Autism Tissue Program

    Science.gov (United States)

    Wintle, Richard F.; Lionel, Anath C.; Hu, Pingzhao; Ginsberg, Stephen D.; Pinto, Dalila; Thiruvahindrapduram, Bhooma; Wei, John; Marshall, Christian R.; Pickett, Jane; Cook, Edwin H.; Scherer, Stephen W.

    2015-01-01

    The Autism Tissue Program (ATP), a science program of Autism Speaks, provides researchers with access to well-characterized postmortem brain tissues. Researchers access these tissues through a peer-reviewed, project-based approval process, and obtain related clinical information from a secure, online informatics portal. However, few of these samples have DNA banked from other sources (such as a blood sample from the same individual), hindering genotype–phenotype correlation and interpretation of gene expression data derived fromthe banked brain tissue. Here, we describe an initiative to extract DNA from Brodmann Area 19, and genotype these samples using both the Affymetrix Genome-Wide Human SNP Array 6.0 and the Illumina Human1M-Duo DNA Analysis BeadChip genome-wide microarray technologies. We additionally verify reported gender, and infer ethnic background from the single nucleotide polymorphism data. We have also used a rigorous, multiple algorithm approach to identify genomic copy number variation (CNV) from these array data. Following an initial proof of principle study using two samples, 52 experimental samples, consisting of 27 subjects with confirmed or suspected autism and related disorders, 5 subjects with cytogenetically visible duplications of 15q, 2 with epilepsy and 18 age-matched normal controls were processed, yielding high-quality genotype data in all cases. The genotype and CNV data are provided via the ATP informatics portal as a resource for the autism research community. PMID:21254448

  9. Influence of liver pathology on markers of postmortem brain tissue quality.

    Science.gov (United States)

    Sheedy, Donna; Say, Meichien; Stevens, Julia; Harper, Clive G; Kril, Jillian J

    2012-01-01

    Postmortem brain tissue provides an important resource to investigate various brain disorders, including those resulting from the effects of alcohol abuse. Unlike the traditionally recognized confounders to tissue quality (e.g., coma, hypoxia), our understanding of the effects of liver disease is incomplete. The aim of this study was to determine the effects of liver pathology, and in particular cirrhosis resulting in hepatic encephalopathy (HE), on 2 postmortem brain tissue quality markers, brain pH and RNA integrity. We measured tissue quality markers in a cohort of alcohol abuse and control cases collected by the NSW Tissue Resource Centre. Cerebellar tissue was used to evaluate both brain pH and RNA quality (as indicated by the RNA integrity number: RIN). A histological assessment was performed on each case to exclude coexisting pathologies (e.g., cerebrovascular disease, hypoxic encephalopathy, neurodegenerative disease) and to assess the presence or absence of HE. Autopsy reports were reviewed for liver pathology and toxicology. Analysis revealed that cases of alcohol abuse had a lower mean (±SD) brain pH, 6.46 (±0.3) as compared with the control mean 6.64 (±0.2). The mean RIN for the alcohol abuse group was 6.97 (±1.3) and controls 7.66 (±0.5). The severity of liver pathology affected both brain pH (p brain pH (p = 0.0019). The results show that the presence of cirrhosis and, more so, HE reduces the pH and RIN of postmortem brain tissue. Copyright © 2011 by the Research Society on Alcoholism.

  10. STEP levels are unchanged in pre-frontal cortex and associative striatum in post-mortem human brain samples from subjects with schizophrenia, bipolar disorder and major depressive disorder.

    Directory of Open Access Journals (Sweden)

    Thomas A Lanz

    Full Text Available Increased protein levels of striatal-enriched tyrosine phosphatase (STEP have recently been reported in postmortem schizophrenic cortex. The present study sought to replicate this finding in a separate cohort of postmortem samples and to extend observations to striatum, including subjects with bipolar disorder and major depressive disorder in the analysis. No statistically significant changes between disease and control subjects were found in STEP mRNA or protein levels in dorsolateral prefrontal cortex or associative striatum. Although samples were matched for several covariates, postmortem interval correlated negatively with STEP protein levels, emphasizing the importance of including these analyses in postmortem studies.

  11. Virtopsy: postmortem imaging of the human heart in situ using MSCT and MRI.

    Science.gov (United States)

    Jackowski, Christian; Schweitzer, Wolf; Thali, Michael; Yen, Kathrin; Aghayev, Emin; Sonnenschein, Martin; Vock, Peter; Dirnhofer, Richard

    2005-04-20

    The rapid further development of computed tomography (CT) and magnetic resonance imaging (MRI) induced the idea to use these techniques for postmortem documentation of forensic findings. Until now, only a few institutes of forensic medicine have acquired experience in postmortem cross-sectional imaging. Protocols, image interpretation and visualization have to be adapted to the postmortem conditions. Especially, postmortem alterations, such as putrefaction and livores, different temperature of the corpse and the loss of the circulation are a challenge for the imaging process and interpretation. Advantages of postmortem imaging are the higher exposure and resolution available in CT when there is no concern for biologic effects of ionizing radiation, and the lack of cardiac motion artifacts during scanning. CT and MRI may become useful tools for postmortem documentation in forensic medicine. In Bern, 80 human corpses underwent postmortem imaging by CT and MRI prior to traditional autopsy until the month of August 2003. Here, we describe the imaging appearance of postmortem alterations--internal livores, putrefaction, postmortem clotting--and distinguish them from the forensic findings of the heart, such as calcification, endocarditis, myocardial infarction, myocardial scarring, injury and other morphological alterations.

  12. Are animal models predictive for human postmortem muscle protein degradation?

    Science.gov (United States)

    Ehrenfellner, Bianca; Zissler, Angela; Steinbacher, Peter; Monticelli, Fabio C; Pittner, Stefan

    2017-11-01

    A most precise determination of the postmortem interval (PMI) is a crucial aspect in forensic casework. Although there are diverse approaches available to date, the high heterogeneity of cases together with the respective postmortal changes often limit the validity and sufficiency of many methods. Recently, a novel approach for time since death estimation by the analysis of postmortal changes of muscle proteins was proposed. It is however necessary to improve the reliability and accuracy, especially by analysis of possible influencing factors on protein degradation. This is ideally investigated on standardized animal models that, however, require legitimization by a comparison of human and animal tissue, and in this specific case of protein degradation profiles. Only if protein degradation events occur in comparable fashion within different species, respective findings can sufficiently be transferred from the animal model to application in humans. Therefor samples from two frequently used animal models (mouse and pig), as well as forensic cases with representative protein profiles of highly differing PMIs were analyzed. Despite physical and physiological differences between species, western blot analysis revealed similar patterns in most of the investigated proteins. Even most degradation events occurred in comparable fashion. In some other aspects, however, human and animal profiles depicted distinct differences. The results of this experimental series clearly indicate the huge importance of comparative studies, whenever animal models are considered. Although animal models could be shown to reflect the basic principles of protein degradation processes in humans, we also gained insight in the difficulties and limitations of the applicability of the developed methodology in different mammalian species regarding protein specificity and methodic functionality.

  13. Correlation of in vivo neuroimaging abnormalities with postmortem human immunodeficiency virus encephalitis and dendritic loss

    DEFF Research Database (Denmark)

    Archibald, Sarah L.; Masliah, Eliezer; Fennema-Notestine, Christine

    2004-01-01

    previous studies have linked brain viral levels to these alterations, other neuropathological mechanisms might also contribute to them. OBJECTIVE: To examine the relationship between findings on premortem magnetic resonance images and postmortem neuropathologic evidence of human immunodeficiency virus (HIV......) encephalitis and neurodegeneration. DESIGN: Morphometric analysis of magnetic resonance imaging in seropositive cases with matched seronegative controls, and the correlation of these volumes to neuropathological measures in autopsied seropositive cases. SETTING: University of California, San Diego, HIV...... Neurobehavioral Research Center. SUBJECTS: Twenty-one seropositive subjects studied at autopsy and 19 seronegative cases. MAIN OUTCOME MEASURES: In vivo structural magnetic resonance imaging data analyzed by quantitative methods, with comparison of volumes from magnetic resonance imaging and neuropathological...

  14. Whole brain analysis of postmortem density changes of grey and white matter on computed tomography by statistical parametric mapping

    Energy Technology Data Exchange (ETDEWEB)

    Nishiyama, Yuichi; Mori, Hiroshi; Katsube, Takashi; Kitagaki, Hajime [Shimane University Faculty of Medicine, Department of Radiology, Izumo-shi, Shimane (Japan); Kanayama, Hidekazu; Tada, Keiji; Yamamoto, Yasushi [Shimane University Hospital, Department of Radiology, Izumo-shi, Shimane (Japan); Takeshita, Haruo [Shimane University Faculty of Medicine, Department of Legal Medicine, Izumo-shi, Shimane (Japan); Kawakami, Kazunori [Fujifilm RI Pharma, Co., Ltd., Tokyo (Japan)

    2017-06-15

    This study examined the usefulness of statistical parametric mapping (SPM) for investigating postmortem changes on brain computed tomography (CT). This retrospective study included 128 patients (23 - 100 years old) without cerebral abnormalities who underwent unenhanced brain CT before and after death. The antemortem CT (AMCT) scans and postmortem CT (PMCT) scans were spatially normalized using our original brain CT template, and postmortem changes of CT values (in Hounsfield units; HU) were analysed by the SPM technique. Compared with AMCT scans, 58.6 % and 98.4 % of PMCT scans showed loss of the cerebral sulci and an unclear grey matter (GM)-white matter (WM) interface, respectively. SPM analysis revealed a significant decrease in cortical GM density within 70 min after death on PMCT scans, suggesting cytotoxic brain oedema. Furthermore, there was a significant increase in the density of the WM, lenticular nucleus and thalamus more than 120 min after death. The SPM technique demonstrated typical postmortem changes on brain CT scans, and revealed that the unclear GM-WM interface on early PMCT scans is caused by a rapid decrease in cortical GM density combined with a delayed increase in WM density. SPM may be useful for assessment of whole brain postmortem changes. (orig.)

  15. Postmortem Brain and Blood Reference Concentrations of Alprazolam, Bromazepam, Chlordiazepoxide, Diazepam, and their Metabolites and a Review of the Literature

    DEFF Research Database (Denmark)

    Skov, Louise; Holm, Karen Marie Dollerup; Johansen, Sys Stybe

    2016-01-01

    , the brain, might be considered. Here we present reference concentrations of femoral blood and brain tissue of selected benzodiazepines (BZDs). Using LC-MS/MS, we quantified alprazolam, bromazepam, chlordiazepoxide, diazepam, and the metabolites desmethyldiazepam, oxazepam and temazepam in postmortem femoral...

  16. UV-laser microdissection and mRNA expression analysis of individual neurons from postmortem Parkinson's disease brains.

    Science.gov (United States)

    Gründemann, Jan; Schlaudraff, Falk; Liss, Birgit

    2011-01-01

    Cell specificity of gene expression analysis is essential to avoid tissue sample related artifacts, in particular when the relative number of target cells present in the compared tissues varies dramatically, e.g., when comparing dopamine neurons in midbrain tissues from control subjects with those from Parkinson's disease (PD) cases. Here, we describe a detailed protocol that combines contact-free UV-laser microdissection and quantitative PCR of reverse-transcribed RNA of individual neurons from postmortem human midbrain tissue from PD patients and unaffected controls. Among expression changes in a variety of dopamine neuron marker, maintenance, and cell-metabolism genes, we found that α-synuclein mRNA levels were significantly elevated in individual neuromelanin-positive dopamine midbrain neurons from PD brains when compared to those from matched controls.

  17. Comprehensive postmortem analyses of intestinal microbiota changes and bacterial translocation in human flora associated mice.

    Directory of Open Access Journals (Sweden)

    Markus M Heimesaat

    Full Text Available BACKGROUND: Postmortem microbiological examinations are performed in forensic and medical pathology for defining uncertain causes of deaths and for screening of deceased tissue donors. Interpretation of bacteriological data, however, is hampered by false-positive results due to agonal spread of microorganisms, postmortem bacterial translocation, and environmental contamination. METHODOLOGY/PRINCIPAL FINDINGS: We performed a kinetic survey of naturally occurring postmortem gut flora changes in the small and large intestines of conventional and gnotobiotic mice associated with a human microbiota (hfa applying cultural and molecular methods. Sacrificed mice were kept under ambient conditions for up to 72 hours postmortem. Intestinal microbiota changes were most pronounced in the ileal lumen where enterobacteria and enterococci increased by 3-5 orders of magnitude in conventional and hfa mice. Interestingly, comparable intestinal overgrowth was shown in acute and chronic intestinal inflammation in mice and men. In hfa mice, ileal overgrowth with enterococci and enterobacteria started 3 and 24 hours postmortem, respectively. Strikingly, intestinal bacteria translocated to extra-intestinal compartments such as mesenteric lymphnodes, spleen, liver, kidney, and cardiac blood as early as 5 min after death. Furthermore, intestinal tissue destruction was characterized by increased numbers of apoptotic cells and neutrophils within 3 hours postmortem, whereas counts of proliferative cells as well as T- and B-lymphocytes and regulatory T-cells decreased between 3 and 12 hours postmortem. CONCLUSIONS/SIGNIFICANCE: We conclude that kinetics of ileal overgrowth with enterobacteria and enterococci in hfa mice can be used as an indicator for compromized intestinal functionality and for more precisely defining the time point of death under defined ambient conditions. The rapid translocation of intestinal bacteria starting within a few minutes after death will help

  18. Comprehensive postmortem analyses of intestinal microbiota changes and bacterial translocation in human flora associated mice.

    Science.gov (United States)

    Heimesaat, Markus M; Boelke, Silvia; Fischer, André; Haag, Lea-Maxie; Loddenkemper, Christoph; Kühl, Anja A; Göbel, Ulf B; Bereswill, Stefan

    2012-01-01

    Postmortem microbiological examinations are performed in forensic and medical pathology for defining uncertain causes of deaths and for screening of deceased tissue donors. Interpretation of bacteriological data, however, is hampered by false-positive results due to agonal spread of microorganisms, postmortem bacterial translocation, and environmental contamination. We performed a kinetic survey of naturally occurring postmortem gut flora changes in the small and large intestines of conventional and gnotobiotic mice associated with a human microbiota (hfa) applying cultural and molecular methods. Sacrificed mice were kept under ambient conditions for up to 72 hours postmortem. Intestinal microbiota changes were most pronounced in the ileal lumen where enterobacteria and enterococci increased by 3-5 orders of magnitude in conventional and hfa mice. Interestingly, comparable intestinal overgrowth was shown in acute and chronic intestinal inflammation in mice and men. In hfa mice, ileal overgrowth with enterococci and enterobacteria started 3 and 24 hours postmortem, respectively. Strikingly, intestinal bacteria translocated to extra-intestinal compartments such as mesenteric lymphnodes, spleen, liver, kidney, and cardiac blood as early as 5 min after death. Furthermore, intestinal tissue destruction was characterized by increased numbers of apoptotic cells and neutrophils within 3 hours postmortem, whereas counts of proliferative cells as well as T- and B-lymphocytes and regulatory T-cells decreased between 3 and 12 hours postmortem. We conclude that kinetics of ileal overgrowth with enterobacteria and enterococci in hfa mice can be used as an indicator for compromized intestinal functionality and for more precisely defining the time point of death under defined ambient conditions. The rapid translocation of intestinal bacteria starting within a few minutes after death will help to distinguish between relevant bacteria and secondary contaminants thus providing

  19. Postmortem succession of gut microbial communities in deceased human subjects

    Directory of Open Access Journals (Sweden)

    Jennifer M. DeBruyn

    2017-06-01

    Full Text Available The human microbiome has demonstrated an importance for the health and functioning in living individuals. However, the fate of the microbiome after death is less understood. In addition to a better understanding of microbe-mediated decomposition processes, postmortem succession of human-associated microbial communities has been suggested as a possible forensic tool for estimating time since death, or postmortem interval (PMI. The objective of our study was to document postmortem changes in human gut bacterial communities. Gut microflora were repeatedly sampled from the caeca of cadavers as they decayed under natural environmental conditions. 16S rRNA gene amplicon sequencing revealed that over time, bacterial richness significantly increased (rs = 0.449 while diversity decreased (rs =  − 0.701. The composition of gut bacterial communities changed in a similar manner over time towards a common decay community. OTUs belonging to Bacteroidales (Bacteroides, Parabacteroides significantly declined while Clostridiales (Clostridium, Anaerosphaera and the fly-associated Gammaproteobacteria Ignatzschineria and Wohlfahrtiimonas increased. Our examination of human caeca microflora in decomposing cadavers adds to the growing literature on postmortem microbial communities, which will ultimately contribute to a better understanding of decomposition processes.

  20. Human wound colonization by Lucilia eximia and Chrysomya rufifacies (Diptera: Calliphoridae): myiasis, perimortem, or postmortem colonization?

    Science.gov (United States)

    Sanford, Michelle R; Whitworth, Terry L; Phatak, Darshan R

    2014-05-01

    The infestation of human or animal tissues by fly larvae has been given distinctive terminology depending on the timing and location of colonization. Wounds and orifices colonized by Diptera in a living human or animal are typically referred to as myiasis. When the colonization occurs after death, it is referred to as postmortem colonization and can be used to estimate the minimum postmortem interval. What happens when the human, as in the case presented here, has a necrotic limb while the human remains alive, at least for a short period of time? The case presented here documents perimortem wound colonization by Lucilia eximia (Wiedemann) and Chrysomya rufifacies (Macquart) and the considerations for approximating development temperatures and estimating the time of colonization (TOC). This represents the first record of L. eximia in human myiasis in the United States and the first record of the co-occurrence of L. eximia and C. rufifacies in human myiasis in the United States. The TOC was estimated using both ambient and body temperature. Insect colonization before death complicates the estimation of TOC and minimum postmortem interval and illustrates the problem of temperature approximation in forensic entomology casework.

  1. Vitreous humour as a potential DNA source for postmortem human identification.

    Directory of Open Access Journals (Sweden)

    Renata Zbiec

    2007-06-01

    Full Text Available PURPOSE
    The aim of this study was the assessment of vitreous humor as a potential DNA for forensic human postmortem identification.

    MATERIAL AND METHODS
    Vitreous humor samples were collected using two alternative approaches from 25 corpses of either sex during autopsies. DNA was extracted by standard organic method. Recovered DNA was quantitiated fluorometrically. AmpFlSTR SGM Plus kit and ABI 310 Genetic Analyzer (Applera were used to obtain genetic profiles.

    RESULTS
    Different DNA yields were quantitated in vitreous body depending on cause of death and sampling approach.

    CONCLUSION
    Vitreous humor is a potential DNA for forensic human postmortem identification depending on a sampling method used.

  2. The Energy Metabolism Dysfunction in Psychiatric Disorders Postmortem Brains: Focus on Proteomic Evidence

    Directory of Open Access Journals (Sweden)

    Giuliana S. Zuccoli

    2017-09-01

    Full Text Available Psychiatric disorders represent a great medical and social challenge and people suffering from these conditions face many impairments regarding personal and professional life. In addition, a mental disorder will manifest itself in approximately one quarter of the world's population at some period of their life. Dysfunction in energy metabolism is one of the most consistent scientific findings associated with these disorders. With this is mind, this review compiled data on disturbances in energy metabolism found by proteomic analyses of postmortem brains collected from patients affected by the most prevalent psychiatric disorders: schizophrenia (SCZ, bipolar disorder (BPD, and major depressive disorder (MDD. We searched in the PubMed database to gather the studies and compiled all the differentially expressed proteins reported in each work. SCZ studies revealed 92 differentially expressed proteins related to energy metabolism, while 95 proteins were discovered in BPD, and 41 proteins in MDD. With the compiled data, it was possible to determine which proteins related to energy metabolism were found to be altered in all the disorders as well as which ones were altered exclusively in one of them. In conclusion, the information gathered in this work could contribute to a better understanding of the impaired metabolic mechanisms and hopefully bring insights into the underlying neuropathology of psychiatric disorders.

  3. Comparison of Metal Levels between Postmortem Brain and Ventricular Fluid in Alzheimer?s Disease and Nondemented Elderly Controls

    OpenAIRE

    Szabo, Steven T.; Harry, G. Jean; Hayden, Kathleen M.; Szabo, David T.; Birnbaum, Linda

    2015-01-01

    An essential metal hypothesis for neurodegenerative disease suggests an alteration in metal homeostasis contributing to the onset and progression of disease. Similar associations have been proposed for nonessential metals. To examine the relationship between metal levels in brain tissue and ventricular fluid (VF), postmortem samples of frontal cortex (FC) and VF from Alzheimer?s disease (AD) cases and nondemented elderly subjects were analyzed for arsenic (As), cadmium (Cd), chromium (Cr), co...

  4. Postmortem examination of human fetuses: a comparison of 2-dimensional ultrasound with invasive autopsy.

    Science.gov (United States)

    Kang, Xin; Shelmerdine, Susan C; Hurtado, Ivan; Bevilacqua, Elisa; Hutchinson, Ciaran; Mandalia, Uday; Segers, Valerie; Cos Sanchez, Teresa; Cannie, Mieke M; Carlin, Andrew; Sebire, Neil J; Arthurs, Owen J; Jani, Jacques C

    2017-08-07

    To compare the diagnostic usefulness of postmortem ultrasound with invasive autopsy in fetuses at different gestational ages. We performed postmortem 2-dimensional ultrasound on 163 fetuses at 13-42 weeks gestation, blinded to clinical details. Logistic regression analysis was used to investigate the effect on non-diagnostic results of gestational age during postmortem ultrasound, presence of maceration, and cause of death. In 123 cases where invasive autopsy was available, the diagnostic accuracy of ultrasound in detecting major organ abnormalities was evaluated, using invasive autopsy as a gold standard. For the fetal brain, a non-diagnostic result was found in 17 (39.5%) of 43 fetuses with maceration and was significantly more common as compared to fetuses without maceration (24 [20.0%] of 120 fetuses [p=0.013]). For the fetal thorax, a non-diagnostic result was found in 15 (34.1%) of 44 fetuses at autopsy. It may therefore play a role as a first-line examination before other virtual autopsy techniques are indicated. This article is protected by copyright. All rights reserved.

  5. Governing the postmortem procurement of human body material for research.

    Science.gov (United States)

    Van Assche, Kristof; Capitaine, Laura; Pennings, Guido; Sterckx, Sigrid

    2015-03-01

    Human body material removed post mortem is a particularly valuable resource for research. Considering the efforts that are currently being made to study the biochemical processes and possible genetic causes that underlie cancer and cardiovascular and neurodegenerative diseases, it is likely that this type of research will continue to gain in importance. However, post mortem procurement of human body material for research raises specific ethical concerns, more in particular with regard to the consent of the research participant. In this paper, we attempt to determine which consent regime should govern the post mortem procurement of body material for research. In order to do so, we assess the various arguments that could be put forward in support of a duty to make body material available for research purposes after death. We argue that this duty does in practice not support conscription but is sufficiently strong to defend a policy of presumed rather than explicit consent.

  6. Ex-vivo MR Volumetry of Human Brain Hemispheres

    Science.gov (United States)

    Kotrotsou, Aikaterini; Bennett, David A.; Schneider, Julie A.; Dawe, Robert J.; Golak, Tom; Leurgans, Sue E.; Yu, Lei; Arfanakis, Konstantinos

    2013-01-01

    Purpose The aims of this work were to: a) develop an approach for ex-vivo MR volumetry of human brain hemispheres that does not contaminate the results of histopathological examination, b) longitudinally assess regional brain volumes postmortem, and c) investigate the relationship between MR volumetric measurements performed in-vivo and ex-vivo. Methods An approach for ex-vivo MR volumetry of human brain hemispheres was developed. Five hemispheres from elderly subjects were imaged ex-vivo longitudinally. All datasets were segmented. The longitudinal behavior of volumes measured ex-vivo was assessed. The relationship between in-vivo and ex-vivo volumetric measurements was investigated in seven elderly subjects imaged both ante-mortem and postmortem. Results The presented approach for ex-vivo MR volumetry did not contaminate the results of histopathological examination. For a period of 6 months postmortem, within-subject volume variation across time points was substantially smaller than inter-subject volume variation. A close linear correspondence was detected between in-vivo and ex-vivo volumetric measurements. Conclusion Regional brain volumes measured with the presented approach for ex-vivo MR volumetry remain relatively unchanged for a period of 6 months postmortem. Furthermore, the linear relationship between in-vivo and ex-vivo MR volumetric measurements suggests that the presented approach captures information linked to ante-mortem macrostructural brain characteristics. PMID:23440751

  7. Magnetic resonance imaging quality and volumes of brain structures from live and postmortem imaging of California sea lions with clinical signs of domoic acid toxicosis.

    Science.gov (United States)

    Montie, Eric W; Wheeler, Elizabeth; Pussini, Nicola; Battey, Thomas W K; Barakos, Jerome; Dennison, Sophie; Colegrove, Kathleen; Gulland, Frances

    2010-09-17

    Our goal in this study was to compare magnetic resonance images and volumes of brain structures obtained alive versus postmortem of California sea lions Zalophus californianus exhibiting clinical signs of domoic acid (DA) toxicosis and those exhibiting normal behavior. Proton density-(PD) and T2-weighted images of postmortem-intact brains, up to 48 h after death, provided similar quality to images acquired from live sea lions. Volumes of gray matter (GM) and white matter (WM) of the cerebral hemispheres were similar to volumes calculated from images acquired when the sea lions were alive. However, cerebrospinal fluid (CSF) volumes decreased due to leakage. Hippocampal volumes from postmortem-intact images were useful for diagnosing unilateral and bilateral atrophy, consequences of DA toxicosis. These volumes were similar to the volumes in the live sea lion studies, up to 48 h postmortem. Imaging formalin-fixed brains provided some information on brain structure; however, images of the hippocampus and surrounding structures were of poorer quality compared to the images acquired alive and postmortem-intact. Despite these issues, volumes of cerebral GM and WM, as well as the hippocampus, were similar to volumes calculated from images of live sea lions and sufficient to diagnose hippocampal atrophy. Thus, postmortem MRI scanning (either intact or formalin-fixed) with volumetric analysis can be used to investigate the acute, chronic and possible developmental effects of DA on the brain of California sea lions.

  8. Genetic control of postnatal human brain growth.

    Science.gov (United States)

    van Dyck, Laura I; Morrow, Eric M

    2017-02-01

    Studies investigating postnatal brain growth disorders inform the biology underlying the development of human brain circuitry. This research is becoming increasingly important for the diagnosis and treatment of childhood neurodevelopmental disorders, including autism and related disorders. Here, we review recent research on typical and abnormal postnatal brain growth and examine potential biological mechanisms. Clinically, brain growth disorders are heralded by diverging head size for a given age and sex, but are more precisely characterized by brain imaging, post-mortem analysis, and animal model studies. Recent neuroimaging and molecular biological studies on postnatal brain growth disorders have broadened our view of both typical and pathological postnatal neurodevelopment. Correlating gene and protein function with brain growth trajectories uncovers postnatal biological mechanisms, including neuronal arborization, synaptogenesis and pruning, and gliogenesis and myelination. Recent investigations of childhood neurodevelopmental and neurodegenerative disorders highlight the underlying genetic programming and experience-dependent remodeling of neural circuitry. To understand typical and abnormal postnatal brain development, clinicians and researchers should characterize brain growth trajectories in the context of neurogenetic syndromes. Understanding mechanisms and trajectories of postnatal brain growth will aid in differentiating, diagnosing, and potentially treating neurodevelopmental disorders.

  9. Establishing the volatile profile of pig carcasses as analogues for human decomposition during the early postmortem period

    Directory of Open Access Journals (Sweden)

    P. Armstrong

    2016-02-01

    Full Text Available Following a mass disaster, it is important that victims are rapidly located as the chances of survival decrease greatly after approximately 48 h. Urban search and rescue (USAR teams may use a range of tools to assist their efforts but detector dogs still remain one of the most effective search tools to locate victims of mass disasters. USAR teams can choose to deploy human scent dogs (trained to locate living victims or human remains detection (HRD dogs (trained to locate deceased victims. However, little is known about the variation between live human scent and postmortem human remains scent and the timeframe during which one type of scent transitions to the other. The aim of the current study was to measure the change in the scent profile of human decomposition analogues during the first 72 h postmortem by measuring the volatile organic compounds (VOCs that comprise the odour. Three pig carcasses (Sus scrofa domesticus L. were placed on a soil surface and allowed to decompose under natural conditions. Decomposition odour was sampled frequently up to 75 h postmortem and analysed using comprehensive two-dimensional gas chromatography – time-of-flight mass spectrometry (GC×GC-TOFMS. A total of 105 postmortem VOCs were identified during the early postmortem period. The VOC profile during the early postmortem period was highly dynamic, changing both hourly and daily. A transition period was observed after 43 h postmortem, where the VOC profile appeared to shift from a distinct antemortem odour to a more generalised postmortem odour. These findings are important in informing USAR teams and their use of detector dogs for disaster victim recovery.

  10. Brain-derived neurotrophic factor and tyrosine kinase B receptor signalling in post-mortem brain of teenage suicide victims.

    Science.gov (United States)

    Pandey, Ghanshyam N; Ren, Xinguo; Rizavi, Hooriyah S; Conley, Robert R; Roberts, Rosalinda C; Dwivedi, Yogesh

    2008-12-01

    Teenage suicide is a major public health concern, but its neurobiology is not very well understood. Stress and major mental disorders are major risk factors for suicidal behaviour, and it has been shown that brain-derived neurotrophic factor (BDNF) and its receptor tyrosine kinase B (TrkB) are not only regulated by stress but are also altered in these illnesses. We therefore examined if BDNF/TrkB signalling is altered in the post-mortem brain of teenage suicide victims. Protein and mRNA expression of BDNF and of TrkB receptors were determined in the prefrontal cortex (PFC), Brodmann's Area 9 (BA 9), and hippocampus obtained from 29 teenage suicide victims and 25 matched normal control subjects. Protein expression was determined using the Western blot technique; mRNA levels by a quantitative RT-PCR technique. The protein expression of BDNF was significantly decreased in the PFC of teenage suicide victims compared with normal control subjects, whereas no change was observed in the hippocampus. Protein expression of TrkB full-length receptors was significantly decreased in both PFC and hippocampus of teenage suicide victims without any significant changes in the truncated form of TrkB receptors. mRNA expression of both BDNF and TrkB was significantly decreased in the PFC and hippocampus of teenage suicide victims compared with normal control subjects. These studies indicate a down-regulation of both BDNF and its receptor TrkB in the PFC and hippocampus of teenage suicide victims, which suggests that stress and altered BDNF may represent a major vulnerability factor in teenage suicidal behaviour.

  11. Region-specific alterations in glucocorticoid receptor expression in the postmortem brain of teenage suicide victims.

    Science.gov (United States)

    Pandey, Ghanshyam N; Rizavi, Hooriyah S; Ren, Xinguo; Dwivedi, Yogesh; Palkovits, Miklós

    2013-11-01

    Abnormal function of the hypothalamic-pituitary-adrenal (HPA) axis has been implicated in the pathophysiology of depression and suicide. The purpose of this study was to test the hypothesis that the reported dysregulation of the HPA axis in suicide may be related to a disturbed feedback inhibition caused by decreased corticoid receptors in the brain. We therefore determined the protein and gene expression of glucocorticoid (GR) and mineralocorticoid receptors (MR) in the postmortem brain of teenage suicide victims and matched normal controls. Protein and mRNA expression of GR (GR-α and GR-β) and MR and the mRNA expression of glucocorticoid-induced leucine zipper (GILZ), a target gene for GR were determined by immunolabeling using Western blot technique and the real-time RT-polymerase chain reaction (qPCR) technique in the prefrontal cortex (PFC), hippocampus, subiculum, and amygdala obtained from 24 teenage suicide victims and 24 teenage control subjects. We observed that protein and gene expression of GR-α was significantly decreased in the PFC and amygdala, but not in the hippocampus or subiculum, of teenage suicide victims compared with normal control subjects. Also, the mRNA levels of GR inducible target gene GILZ was significantly decreased in PFC and amygdaloid nuclei but not in hippocampus compared with controls. In contrast, no significant differences were observed in protein or gene expression of MR in any of the areas studied between teenage suicide victims and normal control subjects. There was no difference in the expression of GR-β in the PFC between suicide victims and normal controls. These results suggested that the observed dysregulation of the HPA axis in suicide may be related to a decreased expression of GR-α and GR inducible genes in the PFC and amygdala of teenage suicide victims. The reason why GR receptors are not dysregulated in the hippocampus or subiculum, presumably two sites of stress action, are not clear at this time. Copyright

  12. Zinc transporters protein level in postmortem brain of depressed subjects and suicide victims.

    Science.gov (United States)

    Rafalo-Ulinska, Anna; Piotrowska, Joanna; Kryczyk, Agata; Opoka, Włodzimierz; Sowa-Kucma, Magdalena; Misztak, Paulina; Rajkowska, Grazyna; Stockmeier, Craig A; Datka, Wojciech; Nowak, Gabriel; Szewczyk, Bernadeta

    2016-12-01

    Major depressive disorder (MDD) is a serious psychiatric illness, associated with an increasing rate of suicide. The pathogenesis of depression may be associated with the disruption of zinc (Zn) homeostasis. In the brain, several proteins that regulate Zn homeostasis are present, including Zn transporters (ZnTs) which remove Zn from the cytosol. The present study was designed to investigate whether depression and suicide are associated with alterations in the expression of the ZnTs protein. Protein levels of ZnT1, ZnT3, ZnT4, ZnT5 and ZnT6 were measured in postmortem brain tissue from two different cohorts. Cohort A contained 10 subjects diagnosed with MDD (7 were suicide victims) and 10 psychiatrically-normal control subjects and cohort B contained 11 non-diagnosed suicide victims and 8 sudden-death control subjects. Moreover, in cohort A we measured protein level of NMDA (GluN2A subunit), AMPA (GluA1 subunit) and 5-HT1A receptors and PSD-95. Proteins were measured in the prefrontal cortex (PFC) using Western blotting. In addition, Zn concentration was measured using a voltammetric method. There was a significant increase in protein levels of ZnT1, ZnT4, ZnT5 in the PFC in MDD, relative to control subjects, while ZnT3 protein level was decreased in MDD. There was no significant difference in the Zn concentration in the PFC between control and MDD subjects. Similarly, in the PFC of suicide victims (non-diagnosed), an increase in protein levels of ZnT1, ZnT4, ZnT5 and ZnT6 was observed. Conversely, protein levels of ZnT3 were decreased in both suicide victims and subjects with MDD, in comparison with control subjects. There was also a significant decrease in the protein level of GluA1, GluN2A, PSD-95 and 5-HT1A in MDD. Our studies suggest that alterations in Zn transport proteins are associated with the pathophysiology of MDD and suicide. Copyright © 2016 Elsevier Ltd. All rights reserved.

  13. Native Mutant Huntingtin in Human Brain

    Science.gov (United States)

    Sapp, Ellen; Valencia, Antonio; Li, Xueyi; Aronin, Neil; Kegel, Kimberly B.; Vonsattel, Jean-Paul; Young, Anne B.; Wexler, Nancy; DiFiglia, Marian

    2012-01-01

    Huntington disease (HD) is caused by polyglutamine expansion in the N terminus of huntingtin (htt). Analysis of human postmortem brain lysates by SDS-PAGE and Western blot reveals htt as full-length and fragmented. Here we used Blue Native PAGE (BNP) and Western blots to study native htt in human postmortem brain. Antisera against htt detected a single band broadly migrating at 575–850 kDa in control brain and at 650–885 kDa in heterozygous and Venezuelan homozygous HD brains. Anti-polyglutamine antisera detected full-length mutant htt in HD brain. There was little htt cleavage even if lysates were pretreated with trypsin, indicating a property of native htt to resist protease cleavage. A soluble mutant htt fragment of about 180 kDa was detected with anti-htt antibody Ab1 (htt-(1–17)) and increased when lysates were treated with denaturants (SDS, 8 m urea, DTT, or trypsin) before BNP. Wild-type htt was more resistant to denaturants. Based on migration of in vitro translated htt fragments, the 180-kDa segment terminated ≈htt 670–880 amino acids. If second dimension SDS-PAGE followed BNP, the 180-kDa mutant htt was absent, and 43–50 kDa htt fragments appeared. Brain lysates from two HD mouse models expressed native full-length htt; a mutant fragment formed if lysates were pretreated with 8 m urea + DTT. Native full-length mutant htt in embryonic HD140Q/140Q mouse primary neurons was intact during cell death and when cell lysates were exposed to denaturants before BNP. Thus, native mutant htt occurs in brain and primary neurons as a soluble full-length monomer. PMID:22375012

  14. Interoperable atlases of the human brain.

    Science.gov (United States)

    Amunts, K; Hawrylycz, M J; Van Essen, D C; Van Horn, J D; Harel, N; Poline, J-B; De Martino, F; Bjaalie, J G; Dehaene-Lambertz, G; Dehaene, S; Valdes-Sosa, P; Thirion, B; Zilles, K; Hill, S L; Abrams, M B; Tass, P A; Vanduffel, W; Evans, A C; Eickhoff, S B

    2014-10-01

    The last two decades have seen an unprecedented development of human brain mapping approaches at various spatial and temporal scales. Together, these have provided a large fundus of information on many different aspects of the human brain including micro- and macrostructural segregation, regional specialization of function, connectivity, and temporal dynamics. Atlases are central in order to integrate such diverse information in a topographically meaningful way. It is noteworthy, that the brain mapping field has been developed along several major lines such as structure vs. function, postmortem vs. in vivo, individual features of the brain vs. population-based aspects, or slow vs. fast dynamics. In order to understand human brain organization, however, it seems inevitable that these different lines are integrated and combined into a multimodal human brain model. To this aim, we held a workshop to determine the constraints of a multi-modal human brain model that are needed to enable (i) an integration of different spatial and temporal scales and data modalities into a common reference system, and (ii) efficient data exchange and analysis. As detailed in this report, to arrive at fully interoperable atlases of the human brain will still require much work at the frontiers of data acquisition, analysis, and representation. Among them, the latter may provide the most challenging task, in particular when it comes to representing features of vastly different scales of space, time and abstraction. The potential benefits of such endeavor, however, clearly outweigh the problems, as only such kind of multi-modal human brain atlas may provide a starting point from which the complex relationships between structure, function, and connectivity may be explored. Copyright © 2014 Elsevier Inc. All rights reserved.

  15. Persistent Angiogenesis in the Autism Brain: An Immunocytochemical Study of Postmortem Cortex, Brainstem and Cerebellum

    Science.gov (United States)

    Azmitia, E. C.; Saccomano, Z. T.; Alzoobaee, M. F.; Boldrini, M.; Whitaker-Azmitia, P. M.

    2016-01-01

    In the current work, we conducted an immunocytochemical search for markers of ongoing neurogenesis (e.g. nestin) in auditory cortex from postmortem sections of autism spectrum disorder (ASD) and age-matched control donors. We found nestin labeling in cells of the vascular system, indicating blood vessels plasticity. Evidence of angiogenesis was…

  16. Transcriptional signatures of schizophrenia in hiPSC-derived NPCs and neurons are concordant with post-mortem adult brains.

    Science.gov (United States)

    Hoffman, Gabriel E; Hartley, Brigham J; Flaherty, Erin; Ladran, Ian; Gochman, Peter; Ruderfer, Douglas M; Stahl, Eli A; Rapoport, Judith; Sklar, Pamela; Brennand, Kristen J

    2017-12-20

    The power of human induced pluripotent stem cell (hiPSC)-based studies to resolve the smaller effects of common variants within the size of cohorts that can be realistically assembled remains uncertain. We identified and accounted for a variety of technical and biological sources of variation in a large case/control schizophrenia (SZ) hiPSC-derived cohort of neural progenitor cells and neurons. Reducing the stochastic effects of the differentiation process by correcting for cell type composition boosted the SZ signal and increased the concordance with post-mortem data sets. We predict a growing convergence between hiPSC and post-mortem studies as both approaches expand to larger cohort sizes. For studies of complex genetic disorders, to maximize the power of hiPSC cohorts currently feasible, in most cases and whenever possible, we recommend expanding the number of individuals even at the expense of the number of replicate hiPSC clones.

  17. Potential Use of Bacterial Community Succession in Decaying Human Bone for Estimating Postmortem Interval.

    Science.gov (United States)

    Damann, Franklin E; Williams, Daniel E; Layton, Alice C

    2015-07-01

    Bacteria are taphonomic agents of human decomposition, potentially useful for estimating postmortem interval (PMI) in late-stage decomposition. Bone samples from 12 individuals and three soil samples were analyzed to assess the effects of decomposition and advancing time on bacterial communities. Results indicated that partially skeletonized remains maintained a presence of bacteria associated with the human gut, whereas bacterial composition of dry skeletal remains maintained a community profile similar to soil communities. Variation in the UniFrac distances was significantly greater between groups than within groups (p decomposition stages. The oligotrophic environment of bone relative to soft tissue and the physical protection of organic substrates may preclude bacterial blooms during the first years of skeletonization. Therefore, community membership (unweighted) may be better for estimating PMI from skeletonized remains than community structure (weighted). © 2015 American Academy of Forensic Sciences.

  18. Visualization of monoamine oxidase in human brain

    Energy Technology Data Exchange (ETDEWEB)

    Fowler, J.S.; Volkow, N.D.; Wang, G.J.; Pappas, N.; Shea, C.; MacGregor, R.R.; Logan, J.

    1996-12-31

    Monoamine oxidase is a flavin enzyme which exists in two subtypes, MAO A and MAO B. In human brain MAO B predominates and is largely compartmentalized in cell bodies of serotonergic neurons and glia. Regional distribution of MAO B was determined by positron computed tomography with volunteers after the administration of deuterium substituted [11C]L-deprenyl. The basal ganglia and thalamus exhibited the greatest concentrations of MAO B with intermediate levels in the frontal cortex and cingulate gyrus while lowest levels were observed in the parietal and temporal cortices and cerebellum. We observed that brain MAO B increases with are in health normal subjects, however the increases were generally smaller than those revealed with post-mortem studies.

  19. Behavioral reversal of lithium effects by four inositol isomers correlates perfectly with biochemical effects on the PI cycle: depletion by chronic lithium of brain inositol is specific to hypothalamus, and inositol levels may be abnormal in postmortem brain from bipolar patients.

    Science.gov (United States)

    Belmaker, R H; Agam, G; van Calker, D; Richards, M H; Kofman, O

    1998-09-01

    The inositol depletion hypothesis of lithium (Li) action has been criticized, because depletion of inositol after chronic Li treatment has not been reproducible, effects of inositol to reverse Li-induced behaviors occurred also with epi-inositol, a unnatural isomer, and because inositol is ubiquitous in brain and hard to relate to the pathogenesis of affective disorder. Therefore, we review our studies showing that lithium depletion of brain inositol occurs chronically in the hypothalamus, a region not previously examined; that behavioral effects of four different inositol isomers including epi-inositol correlate perfectly with their biochemical effects; and that inositol in postmortem human brain is reduced by 25% in frontal cortex of bipolars and suicides as compared with controls. Because inositol in postmortem brain is reduced and not increased in bipolar patients, the relationship between inositol, lithium, and affective disorder is complex.

  20. The effect of repeated freeze-thaw cycles on human muscle tissue visualized by postmortem computed tomography (PMCT)

    NARCIS (Netherlands)

    Klop, Anthony C.; Vester, Marloes E. M.; Colman, Kerri L.; Ruijter, Jan M.; van Rijn, Rick R.; Oostra, Roelof-Jan

    2017-01-01

    The aim of this study was to determine whether effects of repetitive freeze-thaw cycles, with various thawing temperatures, on human muscle tissue can be quantified using postmortem computed tomography (PMCT) technology. An additional objective was to determine the preferred thawing temperature for

  1. Neocortical glial cell numbers in human brains

    DEFF Research Database (Denmark)

    Pelvig, D.P.; Pakkenberg, H.; Stark, A.K.

    2008-01-01

    Stereological cell counting was applied to post-mortem neocortices of human brains from 31 normal individuals, age 18-93 years, 18 females (average age 65 years, range 18-93) and 13 males (average age 57 years, range 19-87). The cells were differentiated in astrocytes, oligodendrocytes, microglia...... while the total astrocyte number is constant through life; finally males have a 28% higher number of neocortical glial cells and a 19% higher neocortical neuron number than females. The overall total number of neocortical neurons and glial cells was 49.3 billion in females and 65.2 billion in males......, a difference of 24% with a high biological variance. These numbers can serve as reference values in quantitative studies of the human neocortex. (C) 2007 Elsevier Inc. All rights reserved Udgivelsesdato: 2008/11...

  2. Higher expression of serotonin 5-HT(2A) receptors in the postmortem brains of teenage suicide victims.

    Science.gov (United States)

    Pandey, Ghanshyam N; Dwivedi, Yogesh; Rizavi, Hooriyah S; Ren, Xinguo; Pandey, Subhash C; Pesold, Christine; Roberts, Rosalinda C; Conley, Robert R; Tamminga, Carol A

    2002-03-01

    Abnormalities of serotonin (5-HT) receptor subtypes have been observed in the postmortem brains of adult suicide victims; however, their role in teenage suicide is unexplored. The authors examined whether 5-HT(2A) receptor subtypes are altered in the postmortem brains of teenage suicide victims. Levels of 5-HT(2A) receptors were determined through examination of [(125)I] LSD binding, protein expression (by use of Western blotting with a specific 5-HT(2A) receptor antibody), and mRNA (by means of quantitative reverse transcription polymerase chain reaction) in the prefrontal cortex, hippocampus, and nucleus accumbens of 15 teenage suicide victims and 15 normal matched teenage subjects. The cellular localization of the 5-HT(2A) receptors was determined by means of gold immunolabeling. The authors observed significantly higher [(125)I]LSD binding in the prefrontal cortex and greater protein expression and mRNA levels in the prefrontal cortex and hippocampus but not in the nucleus accumbens of suicide victims, compared with normal subjects. Greater protein expression was localized on pyramidal cells in cortical layer V but not in other cortical layers or in the surrounding neuropil of the prefrontal cortex of teenage suicide victims. The evidence indicates higher levels of 5-HT(2A) receptor, protein, and mRNA expression in the prefrontal cortex and hippocampus, which have been implicated in emotion, stress, and cognition. There was no higher level in the nucleus accumbens, which has been implicated in drug dependence and craving. Our findings suggest that a higher level of 5-HT(2A) receptors may be one of the neurobiological abnormalities associated with teenage suicide.

  3. Comparison of Metal Levels between Postmortem Brain and Ventricular Fluid in Alzheimer’s Disease and Nondemented Elderly Controls

    Science.gov (United States)

    Szabo, Steven T.; Harry, G. Jean; Hayden, Kathleen M.; Szabo, David T.; Birnbaum, Linda

    2016-01-01

    An essential metal hypothesis for neurodegenerative disease suggests an alteration in metal homeostasis contributing to the onset and progression of disease. Similar associations have been proposed for nonessential metals. To examine the relationship between metal levels in brain tissue and ventricular fluid (VF), postmortem samples of frontal cortex (FC) and VF from Alzheimer’s disease (AD) cases and nondemented elderly subjects were analyzed for arsenic (As), cadmium (Cd), chromium (Cr), cobalt (Co), copper (Cu), iron (Fe), lead (Pb), manganese (Mn), mercury (Hg), nickel (Ni), tin (Sn), vanadium (V), and zinc (Zn) using inductively coupled plasma sector field mass spectrometry. All metals, with exception of equivalent Pb levels, were lower in the VF, compared to FC. Within-subject comparisons demonstrated that VF levels were not representative of levels within brain tissue. The essential metals Cu, Fe, and Zn were found highest in both compartments. Cd, Hg, and V levels in the VF were below the limit of quantification. In AD cases, FC levels of Fe were higher and As and Cd were lower than levels in controls, while levels of As in the VF were higher. Parameter estimates for FC metal levels indicated an association of Braak stage and higher Fe levels and an association of Braak stage and lower As, Mn, and Zn levels. The data showed no evidence of an accumulation of nonessential metals within the AD brain and, with the exception of As, showed no significant shift in the ratio of FC to VF levels to indicate differential clearance. PMID:26721301

  4. Postmortem angiography in computed tomography and magnetic resonance imaging in a case of fatal hemorrhage due to an arterio-venous malformation in the brain.

    Science.gov (United States)

    Franckenberg, Sabine; Schulze, Claudia; Bolliger, Stephan A; Gascho, Dominic; Thali, Michael J; Flach, Patricia M

    2015-05-01

    Autopsy is the traditional gold standard for determining the cause and manner of death in a forensic death investigation. However, postmortem imaging plays an ever-growing role in preliminary examination, even replacing conventional autopsy in some cases. This case report presents a case of massive intra-axial brain hemorrhage due to an arterio-venous malformation. The cause and manner of death were exclusively determined by postmortem radiology. Based on radiological findings, the autopsy was considered redundant and cancelled by the public prosecutor. Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.

  5. Do glutathione levels decline in aging human brain?

    Science.gov (United States)

    Tong, Junchao; Fitzmaurice, Paul S; Moszczynska, Anna; Mattina, Katie; Ang, Lee-Cyn; Boileau, Isabelle; Furukawa, Yoshiaki; Sailasuta, Napapon; Kish, Stephen J

    2016-04-01

    For the past 60 years a major theory of "aging" is that age-related damage is largely caused by excessive uncompensated oxidative stress. The ubiquitous tripeptide glutathione is a major antioxidant defense mechanism against reactive free radicals and has also served as a marker of changes in oxidative stress. Some (albeit conflicting) animal data suggest a loss of glutathione in brain senescence, which might compromise the ability of the aging brain to meet the demands of oxidative stress. Our objective was to establish whether advancing age is associated with glutathione deficiency in human brain. We measured reduced glutathione (GSH) levels in multiple regions of autopsied brain of normal subjects (n=74) aged one day to 99 years. Brain GSH levels during the infancy/teenage years were generally similar to those in the oldest examined adult group (76-99 years). During adulthood (23-99 years) GSH levels remained either stable (occipital cortex) or increased (caudate nucleus, frontal and cerebellar cortices). To the extent that GSH levels represent glutathione antioxidant capacity, our postmortem data suggest that human brain aging is not associated with declining glutathione status. We suggest that aged healthy human brains can maintain antioxidant capacity related to glutathione and that an age-related increase in GSH levels in some brain regions might possibly be a compensatory response to increased oxidative stress. Since our findings, although suggestive, suffer from the generic limitations of all postmortem brain studies, we also suggest the need for "replication" investigations employing the new (1)H MRS imaging procedures in living human brain. Copyright © 2016 Elsevier Inc. All rights reserved.

  6. Cochlear neuropathy in human presbycusis: Confocal analysis of hidden hearing loss in post-mortem tissue.

    Science.gov (United States)

    Viana, Lucas M; O'Malley, Jennifer T; Burgess, Barbara J; Jones, Dianne D; Oliveira, Carlos A C P; Santos, Felipe; Merchant, Saumil N; Liberman, Leslie D; Liberman, M Charles

    2015-09-01

    Recent animal work has suggested that cochlear synapses are more vulnerable than hair cells in both noise-induced and age-related hearing loss. This synaptopathy is invisible in conventional histopathological analysis, because cochlear nerve cell bodies in the spiral ganglion survive for years, and synaptic analysis requires special immunostaining or serial-section electron microscopy. Here, we show that the same quadruple-immunostaining protocols that allow synaptic counts, hair cell counts, neuronal counts and differentiation of afferent and efferent fibers in mouse can be applied to human temporal bones, when harvested within 9 h post-mortem and prepared as dissected whole mounts of the sensory epithelium and osseous spiral lamina. Quantitative analysis of five "normal" ears, aged 54-89 yrs, without any history of otologic disease, suggests that cochlear synaptopathy and the degeneration of cochlear nerve peripheral axons, despite a near-normal hair cell population, may be an important component of human presbycusis. Although primary cochlear nerve degeneration is not expected to affect audiometric thresholds, it may be key to problems with hearing in noise that are characteristic of declining hearing abilities in the aging ear. Copyright © 2015 Elsevier B.V. All rights reserved.

  7. Postmortem morphology and viability of human Peyer's patches in distal ileum: a technical note.

    Science.gov (United States)

    Solarino, Biagio; Di Vella, Giancarlo; Magrone, Thea; Jirillo, Felicita; Tafaro, Angela; Piscitelli, Domenico; Casiello, Michela; Amati, Luigi; Jirillo, Emilio; Tattoli, Lucia

    2009-01-01

    The intestinal mucosa contains a highly specialized immune system which plays a central role in the induction of immune reactions. In the small bowel, Gut-Associated Lymphoid Tissue (GALT) is organized in lymphoid aggregates which are known as Peyer's Patches (PP). Even though human PP involvement in systemic immunity has been described, little is known about their anatomy and morphology and viability. The aim of this study was to examine PP according to their macroscopic anatomy, distribution and cell viability after death. Specimens from the distal ileum were obtained from 72 serial autopsy cases: PP were identified and, parts of them were analyzed for histological examination. Moreover, viability of recovered PP cells was assessed by the trypan blue exclusion test. Most of the PP (90%) were situated on the antimesenteric border of ileum, and the greatest density of PP occurred in the most distal segment. The number of PP varied with age, with the maximum number observed in 21- to 30-years old cadavers. Histological examination showed their remarkable architectural preservation at different post-mortem intervals (PMI), while the mucosal surface underwent autolysis. In 56% of cases PP cells were still viable, especially at PMI < 24 hours after death. These data confirm that human PP are still well preserved in a remarkable percentage of cadavers also several hours after death, and their availability may be helpful in various fields of research.

  8. Decreased catalytic activity and expression of protein kinase C isozymes in teenage suicide victims: a postmortem brain study.

    Science.gov (United States)

    Pandey, Ghanshyam N; Dwivedi, Yogesh; Rizavi, Hooriyah S; Ren, Xinguo; Conley, Robert R

    2004-07-01

    Teenage suicide is a major public health concern. Although there is some understanding of the psychosocial factors associated with teenage suicide, little is known about the neurobiologic factors of teenage suicide. Protein kinase C (PKC) is a critical phosphorylating enzyme in the phosphoinositide signaling pathway (which is involved in many physiologic functions in the brain and has been implicated in the pathogenesis of mood disorders) and is also a target for the therapeutic action of mood-stabilizing drugs. To examine whether the pathogenesis of teenage suicide is associated with changes in PKC. Postmortem brain study. Seventeen teenage suicide victims and 17 nonpsychiatric control subjects. Catalytic activity of PKC and protein and messenger RNA levels of various PKC isozymes, such as PKC alpha, beta, and gamma, were determined in the prefrontal cortex and hippocampus of both groups. Protein kinase C activity was statistically significantly decreased in membrane and cytosol fractions of the prefrontal cortex and hippocampus of teenage suicide victims compared with control subjects. Statistically significant decreases in protein levels of PKC alpha, beta I, beta II, and gamma isozymes were also observed in both of these fractions. These decreases were associated with decreases in levels of their respective messenger RNAs. Because many physiologic functions are mediated through phosphorylation by PKC and because PKC is a target for the therapeutic action of psychoactive drugs, our findings indicate that the pathogenesis of teenage suicide may be associated with abnormalities in PKC and that PKC may be a target for therapeutic intervention in patients with suicidal behavior.

  9. Post-mortem Findings in Huntington's Deep Brain Stimulation: A Moving Target Due to Atrophy

    Directory of Open Access Journals (Sweden)

    Vinata Vedam-Mai

    2016-04-01

    Full Text Available Background: Deep brain stimulation (DBS has been shown to be effective for Parkinson’s disease, essential tremor, and primary dystonia. However, mixed results have been reported in Huntington’s disease (HD. Case Report: A single case of HD DBS was identified from the University of Florida DBS Brain Tissue Network. The clinical presentation, evolution, surgical planning, DBS parameters, clinical outcomes, and brain pathological changes are summarized. Discussion: This case of HD DBS revealed that chorea may improve and be sustained. Minimal histopathological changes were noted around the DBS leads. Severe atrophy due to HD likely changed the DBS lead position relative to the internal capsule.

  10. Comparison of Metal Levels between Postmortem Brain and Ventricular Fluid in Alzheimer's Disease and Nondemented Elderly Controls.

    Science.gov (United States)

    Szabo, Steven T; Harry, G Jean; Hayden, Kathleen M; Szabo, David T; Birnbaum, Linda

    2016-04-01

    An essential metal hypothesis for neurodegenerative disease suggests an alteration in metal homeostasis contributing to the onset and progression of disease. Similar associations have been proposed for nonessential metals. To examine the relationship between metal levels in brain tissue and ventricular fluid (VF), postmortem samples of frontal cortex (FC) and VF from Alzheimer's disease (AD) cases and nondemented elderly subjects were analyzed for arsenic (As), cadmium (Cd), chromium (Cr), cobalt (Co), copper (Cu), iron (Fe), lead (Pb), manganese (Mn), mercury (Hg), nickel (Ni), tin (Sn), vanadium (V), and zinc (Zn) using inductively coupled plasma sector field mass spectrometry. All metals, with exception of equivalent Pb levels, were lower in the VF, compared to FC. Within-subject comparisons demonstrated that VF levels were not representative of levels within brain tissue. The essential metals Cu, Fe, and Zn were found highest in both compartments. Cd, Hg, and V levels in the VF were below the limit of quantification. In AD cases, FC levels of Fe were higher and As and Cd were lower than levels in controls, while levels of As in the VF were higher. Parameter estimates for FC metal levels indicated an association of Braak stage and higher Fe levels and an association of Braak stage and lower As, Mn, and Zn levels. The data showed no evidence of an accumulation of nonessential metals within the AD brain and, with the exception of As, showed no significant shift in the ratio of FC to VF levels to indicate differential clearance. Published by Oxford University Press on behalf of the Society of Toxicology 2015. This work is written by US Government employees and is in the public domain in the US.

  11. Decreased calcineurin immunoreactivity in the postmortem brain of a patient with schizophrenia who had been prescribed the calcineurin inhibitor, tacrolimus, for leukemia

    Directory of Open Access Journals (Sweden)

    Wada A

    2016-07-01

    healthy control group and schizophrenia group, the percentages of CaN-immunoreactive neurons in layers III–VI of the BA46 and the putamen tended to be lower in the tacrolimus case.Conclusion: Tacrolimus may decrease CaN immunoreactivity in some regions of the human brain. Thus, tacrolimus may introduce side effects such as cognitive dysfunction and extrapyramidal symptoms. In addition, we also found that the effect of tacrolimus on CaN immunoreactivity in human brain was stronger than the effect of schizophrenia. Keywords: calcineurin, calcineurin inhibitors, schizophrenia, postmortem brain, immuno­histochemistry

  12. Comparing different post-mortem human samples as DNA sources for downstream genotyping and identification.

    Science.gov (United States)

    Calacal, Gayvelline C; Apaga, Dame Loveliness T; Salvador, Jazelyn M; Jimenez, Joseph Andrew D; Lagat, Ludivino J; Villacorta, Renato Pio F; Lim, Maria Cecilia F; Fortun, Raquel D R; Datar, Francisco A; De Ungria, Maria Corazon A

    2015-11-01

    The capability of DNA laboratories to perform genotyping procedures from post-mortem remains, including those that had undergone putrefaction, continues to be a challenge in the Philippines, a country characterized by very humid and warm conditions all year round. These environmental conditions accelerate the decomposition of human remains that were recovered after a disaster and those that were left abandoned after a crime. When considerable tissue decomposition of human remains has taken place, there is no other option but to extract DNA from bone and/or teeth samples. Routinely, femur shafts are obtained from recovered bodies for human identification because the calcium matrix protects the DNA contained in the osteocytes. In the Philippines, there is difficulty in collecting femur samples after natural disasters or even human-made disasters, because these events are usually characterized by a large number of fatalities. Identification of casualties is further delayed by limitation in human and material resources. Hence, it is imperative to test other types of biological samples that are easier to collect, transport, process and store. We analyzed DNA that were obtained from body fluid, bone marrow, muscle tissue, clavicle, femur, metatarsal, patella, rib and vertebral samples from five recently deceased untreated male cadavers and seven male human remains that were embalmed, buried for ∼ 1 month and then exhumed. The bodies had undergone different environmental conditions and were in various stages of putrefaction. A DNA extraction method utilizing a detergent-washing step followed by an organic procedure was used. The utility of bone marrow and vitreous fluid including bone marrow and vitreous fluid that was transferred on FTA(®) cards and subjected to autosomal STR and Y-STR DNA typing were also evaluated. DNA yield was measured and the presence or absence of PCR inhibitors in DNA extracts was assessed using Plexor(®)HY. All samples were amplified using

  13. Comparison of two different procedures for quantification of drugs of abuse in postmortem brain samples

    DEFF Research Database (Denmark)

    Reiter, Birgit; Stimpfl, Thomas; Holm, Karen Marie Dollerup

    The aim of this study was to compare a routine method for qualitative and quantitative analysis of body-fluids and tissue samples developed in Vienna to a routine method developed for blood used in Copenhagen. No optimization was performed beforehand on the Copenhagen method to accommodate for the...... for the use of brain tissue....

  14. The black soldier fly Hermetia illucens (Diptera: Stratiomyidae) as a potential measure of human postmortem interval: observations and case histories.

    Science.gov (United States)

    Lord, W D; Goff, M L; Adkins, T R; Haskell, N H

    1994-01-01

    The black soldier fly, Hermetia illucens (L.), has been shown to be a ubiquitous inhabitant of both surface and buried human remains throughout the southern, central and western United States and Hawaii. Unlike most other species of forensically important Diptera, this species frequently dominates bodies in the dry/post decay stage of decomposition. Adults of the black soldier fly appear to initiate oviposition (egg laying) 20 to 30 days postmortem. Even at warm temperatures (27.8 degrees C), subsequent completion of the life cycle can require an additional 55 days. Life history data for H. illucens, when used in combination with data for other cohabiting arthropod species and viewed in the context of local environmental conditions, can provide medicolegal investigators with valuable parameters for estimating the postmortem intervals for badly decomposed remains.

  15. Optimized lower leg injury probability curves from postmortem human subject tests under axial impacts.

    Science.gov (United States)

    Yoganandan, Narayan; Arun, Mike W J; Pintar, Frank A; Szabo, Aniko

    2014-01-01

    Derive optimum injury probability curves to describe human tolerance of the lower leg using parametric survival analysis. The study reexamined lower leg postmortem human subjects (PMHS) data from a large group of specimens. Briefly, axial loading experiments were conducted by impacting the plantar surface of the foot. Both injury and noninjury tests were included in the testing process. They were identified by pre- and posttest radiographic images and detailed dissection following the impact test. Fractures included injuries to the calcaneus and distal tibia-fibula complex (including pylon), representing severities at the Abbreviated Injury Score (AIS) level 2+. For the statistical analysis, peak force was chosen as the main explanatory variable and the age was chosen as the covariable. Censoring statuses depended on experimental outcomes. Parameters from the parametric survival analysis were estimated using the maximum likelihood approach and the dfbetas statistic was used to identify overly influential samples. The best fit from the Weibull, log-normal, and log-logistic distributions was based on the Akaike information criterion. Plus and minus 95% confidence intervals were obtained for the optimum injury probability distribution. The relative sizes of the interval were determined at predetermined risk levels. Quality indices were described at each of the selected probability levels. The mean age, stature, and weight were 58.2±15.1 years, 1.74±0.08 m, and 74.9±13.8 kg, respectively. Excluding all overly influential tests resulted in the tightest confidence intervals. The Weibull distribution was the most optimum function compared to the other 2 distributions. A majority of quality indices were in the good category for this optimum distribution when results were extracted for 25-, 45- and 65-year-olds at 5, 25, and 50% risk levels age groups for lower leg fracture. For 25, 45, and 65 years, peak forces were 8.1, 6.5, and 5.1 kN at 5% risk; 9.6, 7.7, and 6.1 k

  16. Postmortem biochemistry

    Directory of Open Access Journals (Sweden)

    Mukaddes Gürler

    2014-12-01

    Full Text Available Postmortem biochemistry is becoming more important in forensic pathology. Involving of biochemical investigations full autopsy can provide to detect divers pathologic conditions such as antemortem acute/chronic diseases, fatal metabolic conditions, survival time, postmortem biochemical changes, and the source of analytes. Biochemical tests may be usefull where the morphological examinations cannot lighten the fatal pathology (Diabetes Mellitus (DM, alcoholic ketoacidosis, sepsis, electrolytic disorders. This article presents the analytes that may be useful in forensic medicine upon the studies performed and published in the literature.

  17. Optical properties of rabbit brain in the red and near-infrared: changes observed under in vivo, postmortem, frozen, and formalin-fixated conditions

    Science.gov (United States)

    Pitzschke, Andreas; Lovisa, Blaise; Seydoux, Olivier; Haenggi, Matthias; Oertel, Markus F.; Zellweger, Matthieu; Tardy, Yanik; Wagnières, Georges

    2015-02-01

    The outcome of light-based therapeutic approaches depends on light propagation in biological tissues, which is governed by their optical properties. The objective of this study was to quantify optical properties of brain tissue in vivo and postmortem and assess changes due to tissue handling postmortem. The study was carried out on eight female New Zealand white rabbits. The local fluence rate was measured in the VIS/NIR range in the brain in vivo, just postmortem, and after six weeks' storage of the head at -20°C or in 10% formaldehyde solution. Only minimal changes in the effective attenuation coefficient μeff were observed for two methods of sacrifice, exsanguination or injection of KCl. Under all tissue conditions, μeff decreased with increasing wavelengths. After long-term storage for six weeks at -20°C, μeff decreased, on average, by 15 to 25% at all wavelengths, while it increased by 5 to 15% at all wavelengths after storage in formaldehyde. We demonstrated that μeff was not very sensitive to the method of animal sacrifice, that tissue freezing significantly altered tissue optical properties, and that formalin fixation might affect the tissue's optical properties.

  18. Understanding the cellular and molecular alterations in PTSD brains : The necessity of post-mortem brain tissue

    NARCIS (Netherlands)

    De Lange, G.

    2017-01-01

    The personal, social and economic burden of post-traumatic stress disorder (PTSD) is high and therapeutic approaches are only partially effective. Therefore, there is an urgent need to understand the cellular and molecular alterations in PTSD brains in order to design more effective treatment

  19. Histology-derived volumetric annotation of the human hippocampal subfields in postmortem MRI

    OpenAIRE

    Adler, Daniel H.; Pluta, John; Kadivar, Salmon; Craige, Caryne; Gee, James C.; Avants, Brian B.; Yushkevich, Paul A.

    2013-01-01

    Recently, there has been a growing effort to analyze the morphometry of hippocampal subfields using both in vivo and postmortem magnetic resonance imaging (MRI). However, given that boundaries between subregions of the hippocampal formation (HF) are conventionally defined on the basis of microscopic features that often lack discernible signature in MRI, subfield delineation in MRI literature has largely relied on heuristic geometric rules, the validity of which with respect to the underlying ...

  20. Application of stereological methods to estimate post-mortem brain surface area using 3T MRI

    DEFF Research Database (Denmark)

    Furlong, Carolyn; García-Fiñana, Marta; Puddephat, Michael

    2013-01-01

    The Cavalieri and Vertical Sections methods of design based stereology were applied in combination with 3 tesla (i.e. 3T) Magnetic Resonance Imaging (MRI) to estimate cortical and subcortical volume, area of the pial surface, area of the grey-white matter boundary, and thickness of the cerebral...... cortex. The material comprises eight human cadaveric cerebri which had been separated into sixteen cerebral hemisphere specimens prior to embedding in agar gel. The results from MRI were compared with corresponding 'gold standard' values subsequently obtained by application of the same methodology using...... physical sectioning of the specimens. 95% agreement intervals revealed poor agreement between MR imaging and physical sectioning, specially for pial surface and thickness, as well as cerebral cortex and subcortex volumes. On average, pial surface area was estimated to be almost half the extent using MRI...

  1. Educating the Human Brain. Human Brain Development Series

    Science.gov (United States)

    Posner, Michael I.; Rothbart, Mary K.

    2006-01-01

    "Educating the Human Brain" is the product of a quarter century of research. This book provides an empirical account of the early development of attention and self regulation in infants and young children. It examines the brain areas involved in regulatory networks, their connectivity, and how their development is influenced by genes and…

  2. Brain region specific alterations in the protein and mRNA levels of protein kinase A subunits in the post-mortem brain of teenage suicide victims.

    Science.gov (United States)

    Pandey, Ghanshyam N; Dwivedi, Yogesh; Ren, Xinguo; Rizavi, Hooriyah S; Mondal, Amal C; Shukla, Pradeep K; Conley, Robert R

    2005-08-01

    Protein kinase A (PKA), a critical component of the adenylyl cyclase signaling system, phosphorylates crucial proteins and has been implicated in the pathophysiology of depression and suicide. The objective of the study was to examine if changes in PKA activity or in the protein and messenger RNA (mRNA) expression of any of its subunits are related to the pathophysiology of teenage suicide. We determined PKA activity and the protein and mRNA expression of different subunits of PKA in cytosol and membrane fractions obtained from the prefrontal cortex, (PFC) hippocampus, and nucleus accumbens (NA) of post-mortem brain from 17 teenage suicide victims and 17 nonpsychiatric control subjects. PKA activity was significantly decreased in the PFC but not the hippocampus of teenage suicide victims as compared with controls. However, the protein and mRNA expression of only two PKA subunits, that is, PKA RIalpha and PKA RIbeta, but not any other subunits were significantly decreased in both membrane and cytosol fractions of the PFC and protein expression of RIalpha and RIbeta in the NA of teenage suicide victims as compared to controls. A decrease in protein and mRNA expression of two specific PKA subunits may be associated with the pathogenesis of teenage suicide, and this decrease may be brain region specific, which may be related to the specific behavioral functions associated with these brain areas. Whether these changes in PKA subunits are related to suicidal behavior or are a result of suicide or are specific to suicide is not clear at this point.

  3. Postmortem changes in lungs in severe closed traumatic brain injury complicated by acute respiratory failure

    Directory of Open Access Journals (Sweden)

    V. A. Tumanskiy

    2013-08-01

    Full Text Available V.А. Tumanskіy, S.І. Ternishniy, L.M. Tumanskaya Pathological changes in the lungs were studied in the work of 42 patiens who died from severe closed intracranial injury (SCII. It was complicated with acute respiratory insufficient (ARI. The most modified subpleural areas were selected from every lobe of the lungs for pathological studies. Prepared histological sections were stained by means of hemotoxylin and eosin and by Van Giеson for light microscopy. The results of the investigation have shown absence of the significant difference of pathological changes in the lungs of patients who died from ARI because of severe brain injury and traumatic intracranial hemorrhage. Pathognomic pathological changes in the lungs as a result of acute lung injury syndrome (ALIS were found in deceased patients on the third day since the SCII (n=8. There was a significant bilateral interstitial edema and mild alveolar edema with the presence of red and blood cells in the alveoli, vascular plethora of the septum interalveolar and stasis of blood in the capillaries, the slight pericapillary leukocyte infiltration, subpleural hemorrhage and laminar pulmonary atelectasis. In deceased patients on 4-6 days after SCII that was complicated with ARI (n=14, morphological changes had been detected in the lungs. It was pathognomic for acute respiratory distress syndrome (ARDS with local pneumonic to be layered. A significant interstitial pulmonary edema was observed in the respiratory part of the lungs. The edema has spread from the walls of the alveoli into the interstitial spaces of the bronchioles and blood vessels, and also less marked serous-hemorrhagic alveolar edema with presence of the fibrin in the alveoli and macrophages. The ways of intrapleural lymphatic drainage were dilatated. Histopathological changes in the lungs of those who died on the 7-15th days after severe closed craniocerebral injury with ARI to be complicated (n=12 have been indicative of two

  4. Antipsychotic drugs attenuate aberrant DNA methylation of DTNBP1 (dysbindin) promoter in saliva and post-mortem brain of patients with schizophrenia and Psychotic bipolar disorder.

    Science.gov (United States)

    Abdolmaleky, Hamid M; Pajouhanfar, Sara; Faghankhani, Masoomeh; Joghataei, Mohammad Taghi; Mostafavi, Ashraf; Thiagalingam, Sam

    2015-12-01

    Due to the lack of genetic association between individual genes and schizophrenia (SCZ) pathogenesis, the current consensus is to consider both genetic and epigenetic alterations. Here, we report the examination of DNA methylation status of DTNBP1 promoter region, one of the most credible candidate genes affected in SCZ, assayed in saliva and post-mortem brain samples. The Illumina DNA methylation profiling and bisulfite sequencing of representative samples were used to identify methylation status of the DTNBP1 promoter region. Quantitative methylation specific PCR (qMSP) was employed to assess methylation of DTNBP1 promoter CpGs flanking a SP1 binding site in the saliva of SCZ patients, their first-degree relatives and control subjects (30, 15, and 30/group, respectively) as well as in post-mortem brains of patients with SCZ and bipolar disorder (BD) versus controls (35/group). qRT-PCR was used to assess DTNBP1 expression. We found DNA hypermethylation of DTNBP1 promoter in the saliva of SCZ patients (∼12.5%, P = 0.036), particularly in drug-naïve patients (∼20%, P = 0.011), and a trend toward hypermethylation in their first-degree relatives (P = 0.085) versus controls. Analysis of post-mortem brain samples revealed an inverse correlation between DTNBP1 methylation and expression, and normalization of this epigenetic change by classic antipsychotic drugs. Additionally, BD patients with psychotic depression exhibited higher degree of methylation versus other BD patients (∼80%, P = 0.025). DTNBP1 promoter DNA methylation may become a key element in a panel of biomarkers for diagnosis, prevention, or therapy in SCZ and at risk individuals pending confirmatory studies with larger sample sizes to attain a higher degree of significance. © 2015 Wiley Periodicals, Inc.

  5. Associating transcription factors and conserved RNA structures with gene regulation in the human brain

    DEFF Research Database (Denmark)

    Hecker, Nikolai; Seemann, Stefan E.; Silahtaroglu, Asli

    2017-01-01

    Anatomical subdivisions of the human brain can be associated with different neuronal functions. This functional diversification is reflected by differences in gene expression. By analyzing post-mortem gene expression data from the Allen Brain Atlas, we investigated the impact of transcription...... factors (TF) and RNA secondary structures on the regulation of gene expression in the human brain. First, we modeled the expression of a gene as a linear combination of the expression of TFs. We devised an approach to select robust TF-gene interactions and to determine localized contributions to gene...

  6. Functional neuroimaging of post-mortem tissue: lithium-pilocarpine seized rats express reduced brain mass and proportional reductions of left ventral cerebral theta spectral power

    Directory of Open Access Journals (Sweden)

    Nicolas Rouleau

    2016-10-01

    Full Text Available Structural imaging tools can be used to identify neuropathology in post-mortem tissue whereas functional imaging tools including quantitative electroencephalography (QEEG are thought to be restricted for use in living subjects. We are not aware of any study which has used electrophysiological methods decades after death to infer pathology. We therefore attempted to discriminate between chemically preserved brains which had incurred electrical seizures and those that did not using functional imaging. Our data indicate that modified QEEG technology involving needle electrodes embedded within chemically fixed neural tissue can be used to discriminate pathology. Forty (n = 40 rat brains preserved in ethanol-formalin-acetic acid (EFA were probed by needle electrodes inserted into the dorsal and ventral components of the left and right cerebral hemispheres. Raw microvolt potentials were converted to spectral power densities within classical electroencephalographic frequency bands (1.5 Hz to 40 Hz. Brain mass differences were shown to scale with left hemispheric ventral theta-band spectral power densities in lithium-pilocarpine seized rats. This relationship was not observed in non-seized rats. A conspicuous absence of pathological indicators within dorsal regions as inferred by microvolt fluctuations was expected given the known localization of post-ictal damage in lithium-pilocarpine seized rats. Together, the data demonstrate that post-mortem neuroimaging is both possible and potentially useful as a means to identify neuropathology without structural imaging techniques or dissection.

  7. 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.

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

    Directory of Open Access Journals (Sweden)

    Lior Kirsch

    2016-08-01

    Full Text Available 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. Post-mortem whole-body magnetic resonance imaging of human fetuses: a comparison of 3-T vs. 1.5-T MR imaging with classical autopsy

    Energy Technology Data Exchange (ETDEWEB)

    Kang, Xin; Bevilacqua, Elisa; Cos Sanchez, Teresa; Jani, Jacques C. [University Hospital Brugmann, Universite Libre de Bruxelles, Department of Obstetrics and Gynecology, Fetal Medicine Unit, Brussels (Belgium); Cannie, Mieke M. [University Hospital Brugmann, Universite Libre de Bruxelles, Department of Radiology, Brussels (Belgium); Vrije Universiteit Brussel, Department of Radiology, UZ Brussel, Brussels (Belgium); Arthurs, Owen J.; Sebire, Neil J. [Great Ormond Street Hospital for Children NHS Foundation Trust, London (United Kingdom); UCL Institute of Child Health, London (United Kingdom); Segers, Valerie; Fourneau, Catherine [University Hospital Brugmann, Universite Libre de Bruxelles, Department of Fetopathology, Brussels (Belgium)

    2017-08-15

    To prospectively compare diagnostic accuracy of fetal post-mortem whole-body MRI at 3-T vs. 1.5-T. Between 2012 and 2015, post-mortem MRI at 1.5-T and 3-T was performed in fetuses after miscarriage/stillbirth or termination. Clinical MRI diagnoses were assessed using a confidence diagnostic score and compared with classical autopsy to derive a diagnostic error score. The relation of diagnostic error for each organ group with gestational age was calculated and 1.5-T with 3-T was compared with accuracy analysis. 135 fetuses at 12-41 weeks underwent post-mortem MRI (followed by conventional autopsy in 92 fetuses). For all organ groups except the brain, and for both modalities, the diagnostic error decreased with gestation (P < 0.0001). 3-T MRI diagnostic error was significantly lower than that of 1.5-T for all anatomic structures and organ groups, except the orbits and brain. This difference was maintained for fetuses <20 weeks gestation. Moreover, 3-T was associated with fewer non-diagnostic scans and greater concordance with classical autopsy than 1.5-T MRI, especially for the thorax, heart and abdomen in fetuses <20 weeks. Post-mortem fetal 3-T MRI improves confidence scores and overall accuracy compared with 1.5-T, mainly for the thorax, heart and abdomen of fetuses <20 weeks of gestation. (orig.)

  10. Predicting the postmortem submersion interval for human remains recovered from U.K. waterways.

    Science.gov (United States)

    Heaton, Vivienne; Lagden, Abigail; Moffatt, Colin; Simmons, Tal

    2010-03-01

    This article aims to increase accuracy in estimating the postmortem submersion interval (PMSI) for bodies recovered from rivers in the United Kingdom. Data were collected from closed case files, crime scene reports, and autopsy files concerning bodies recovered over a 15-year period from the River Clyde, Scotland, and the River Mersey and canals in northwest England. One hundred and eighty-seven cases met the study criteria and were scored by quantifying the overall amount of decomposition observed in each case. Statistical analysis showed that the duration of a body's submergence in water and the temperatures to which it was exposed, as measured in accumulated degree days (ADD), had a significant effect on the decay process. Further analysis indicated that there were no significant differences in decomposition between the waterways. By combining the data from all study samples, it was possible to produce a single linear regression model for predicting ADD from observed decomposition.

  11. Neurofibrillary tangle pathology and Braak staging in chronic epilepsy in relation to traumatic brain injury and hippocampal sclerosis: a post-mortem study.

    Science.gov (United States)

    Thom, Maria; Liu, Joan Y W; Thompson, Pam; Phadke, Rahul; Narkiewicz, Marta; Martinian, Lillian; Marsdon, Derek; Koepp, Matthias; Caboclo, Luis; Catarino, Claudia B; Sisodiya, Sanjay M

    2011-10-01

    The long-term pathological effects of chronic epilepsy on normal brain ageing are unknown. Previous clinical and epidemiological studies show progressive cognitive decline in subsets of patients and an increased prevalence of Alzheimer's disease in epilepsy. In a post-mortem series of 138 patients with long-term, mainly drug-resistant epilepsy, we carried out Braak staging for Alzheimer's disease neurofibrillary pathology using tau protein immunohistochemistry. The stages were compared with clinicopathological factors, including seizure history and presence of old traumatic brain injury. Overall, 31% of cases were Braak Stage 0, 36% Stage I/II, 31% Stage III/IV and 2% Stage V/VI. The mean age at death was 56.5 years and correlated with Braak stage (P pathological evidence of traumatic brain injury that was significantly associated with higher Braak stages (P brain injury (P pathology. In summary, there is evidence of accelerated brain ageing in severe chronic epilepsy although progression to high Braak stages was infrequent. Traumatic brain injury, but not seizures, was associated with tau protein accumulation in this series. It is likely that Alzheimer's disease pathology is not the sole explanation for cognitive decline associated with epilepsy.

  12. Postmortem imaging: MDCT features of postmortem change and decomposition.

    Science.gov (United States)

    Levy, Angela D; Harcke, Howard Theodore; Mallak, Craig T

    2010-03-01

    Multidetector computed tomography (MDCT) has emerged as an effective imaging technique to augment forensic autopsy. Postmortem change and decomposition are always present at autopsy and on postmortem MDCT because they begin to occur immediately upon death. Consequently, postmortem change and decomposition on postmortem MDCT should be recognized and not mistaken for a pathologic process or injury. Livor mortis increases the attenuation of vasculature and dependent tissues on MDCT. It may also produce a hematocrit effect with fluid levels in the large caliber blood vessels and cardiac chambers from dependent layering erythrocytes. Rigor mortis and algor mortis have no specific MDCT features. In contrast, decomposition through autolysis, putrefaction, and insect and animal predation produce dramatic alterations in the appearance of the body on MDCT. Autolysis alters the attenuation of organs. The most dramatic autolytic changes on MDCT are seen in the brain where cerebral sulci and ventricles are effaced and gray-white matter differentiation is lost almost immediately after death. Putrefaction produces a pattern of gas that begins with intravascular gas and proceeds to gaseous distension of all anatomic spaces, organs, and soft tissues. Knowledge of the spectrum of postmortem change and decomposition is an important component of postmortem MDCT interpretation.

  13. Diagnosis, management and post-mortem findings of a human case of rabies imported into the United Kingdom from India: a case report.

    Science.gov (United States)

    Pathak, Smriti; Horton, Daniel L; Lucas, Sebastian; Brown, David; Quaderi, Shumonta; Polhill, Sara; Walker, David; Nastouli, Eleni; Núñez, Alejandro; Wise, Emma L; Fooks, Anthony R; Brown, Michael

    2014-04-07

    Human rabies infection continues to be a significant public health burden globally, and is occasionally imported to high income settings where the Milwaukee Protocol for intensive care management has recently been employed, with limited success in improving survival. Access to molecular diagnostics, pre- and post-mortem, and documentation of pathophysiological responses while using the Milwaukee protocol, can add useful insights for the future of rabies management. A 58-year-old British Asian woman was referred to a regional general hospital in the UK with hydrophobia, anxiety and confusion nine weeks after receiving a dog bite in North West India. Nuchal skin biopsy, saliva, and a skin biopsy from the site of the dog bite wound, taken on the day of admission, all demonstrated the presence of rabies virus RNA. Within 48 hours sequence analysis of viral RNA confirmed the diagnosis and demonstrated that the virus was a strain closely related to canine rabies viruses circulating in South Asia. Her condition deteriorated rapidly with increased agitation and autonomic dysfunction. She was heavily sedated and intubated on the day after admission, treated according to a modified Milwaukee protocol, and remained stable until she developed heart block and profound acidosis and died on the eighth day. Analysis of autopsy samples showed a complete absence of rabies neutralizing antibody in cerebrospinal fluid and serum, and corresponding high levels of virus antigen and nucleic acid in brain and cerebrospinal fluid. Quantitative PCR showed virus was also distributed widely in peripheral tissues despite mild or undetectable histopathological changes. Vagus nerve branches in the heart showed neuritis, a probable Negri body but no demonstrable rabies antigen. Rapid molecular diagnosis and strain typing is helpful in the management of human rabies infection. Post-mortem findings such as vagal neuritis highlight clinically important effects on the cardiovascular system which are

  14. brain-coX: investigating and visualising gene co-expression in seven human brain transcriptomic datasets.

    Science.gov (United States)

    Freytag, Saskia; Burgess, Rosemary; Oliver, Karen L; Bahlo, Melanie

    2017-06-08

    The pathogenesis of neurological and mental health disorders often involves multiple genes, complex interactions, as well as brain- and development-specific biological mechanisms. These characteristics make identification of disease genes for such disorders challenging, as conventional prioritisation tools are not specifically tailored to deal with the complexity of the human brain. Thus, we developed a novel web-application-brain-coX-that offers gene prioritisation with accompanying visualisations based on seven gene expression datasets in the post-mortem human brain, the largest such resource ever assembled. We tested whether our tool can correctly prioritise known genes from 37 brain-specific KEGG pathways and 17 psychiatric conditions. We achieved average sensitivity of nearly 50%, at the same time reaching a specificity of approximately 75%. We also compared brain-coX's performance to that of its main competitors, Endeavour and ToppGene, focusing on the ability to discover novel associations. Using a subset of the curated SFARI autism gene collection we show that brain-coX's prioritisations are most similar to SFARI's own curated gene classifications. brain-coX is the first prioritisation and visualisation web-tool targeted to the human brain and can be freely accessed via http://shiny.bioinf.wehi.edu.au/freytag.s/ .

  15. Human brain diffusion tensor imaging at submillimeter isotropic resolution on a 3Tesla clinical MRI scanner.

    Science.gov (United States)

    Chang, Hing-Chiu; Sundman, Mark; Petit, Laurent; Guhaniyogi, Shayan; Chu, Mei-Lan; Petty, Christopher; Song, Allen W; Chen, Nan-kuei

    2015-09-01

    The advantages of high-resolution diffusion tensor imaging (DTI) have been demonstrated in a recent post-mortem human brain study (Miller et al., NeuroImage 2011;57(1):167-181), showing that white matter fiber tracts can be much more accurately detected in data at a submillimeter isotropic resolution. To our knowledge, in vivo human brain DTI at a submillimeter isotropic resolution has not been routinely achieved yet because of the difficulty in simultaneously achieving high resolution and high signal-to-noise ratio (SNR) in DTI scans. Here we report a 3D multi-slab interleaved EPI acquisition integrated with multiplexed sensitivity encoded (MUSE) reconstruction, to achieve high-quality, high-SNR and submillimeter isotropic resolution (0.85×0.85×0.85mm(3)) in vivo human brain DTI on a 3Tesla clinical MRI scanner. In agreement with the previously reported post-mortem human brain DTI study, our in vivo data show that the structural connectivity networks of human brains can be mapped more accurately and completely with high-resolution DTI as compared with conventional DTI (e.g., 2×2×2mm(3)). Copyright © 2015 Elsevier Inc. All rights reserved.

  16. Postmortem examination of patient H.M.’s brain based on histological sectioning and digital 3D reconstruction

    Science.gov (United States)

    Annese, Jacopo; Schenker-Ahmed, Natalie M.; Bartsch, Hauke; Maechler, Paul; Sheh, Colleen; Thomas, Natasha; Kayano, Junya; Ghatan, Alexander; Bresler, Noah; Frosch, Matthew P.; Klaming, Ruth; Corkin, Suzanne

    2014-01-01

    Modern scientific knowledge of how memory functions are organized in the human brain originated from the case of Henry G. Molaison (H.M.), an epileptic patient whose amnesia ensued unexpectedly following a bilateral surgical ablation of medial temporal lobe structures, including the hippocampus. The neuroanatomical extent of the 1953 operation could not be assessed definitively during H.M.’s life. Here we describe the results of a procedure designed to reconstruct a microscopic anatomical model of the whole brain and conduct detailed 3D measurements in the medial temporal lobe region. This approach, combined with cellular-level imaging of stained histological slices, demonstrates a significant amount of residual hippocampal tissue with distinctive cytoarchitecture. Our study also reveals diffuse pathology in the deep white matter and a small, circumscribed lesion in the left orbitofrontal cortex. The findings constitute new evidence that may help elucidate the consequences of H.M.’s operation in the context of the brain’s overall pathology.

  17. A Novel Method for Quantifying Human In Situ Whole Brain Deformation Under Rotational Loading Using Sonomicrometry.

    Science.gov (United States)

    Alshareef, Ahmed; Giudice, J Sebastian; Forman, Jason; Salzar, Robert S; Panzer, Matthew B

    2017-11-27

    Traumatic brain injuries are one of the least understood injuries to the body. Finite element (FE) models of the brain have been crucial for understanding concussion and for developing injury mitigation systems; however, the experimental brain deformation data currently used to validate these models are limited. The objective of this study was to develop a methodology for the investigation of in situ three-dimensional brain deformation during pure rotational loading of the head, using sonomicrometry. Sonomicrometry uses ultrasonic pulses to measure the dynamic distances between piezoelectric crystals implanted in any sound-transmitting media. A human cadaveric head-neck specimen was acquired 14 hours post-mortem and was instrumented with an array of 32 small sonomicrometry crystals embedded in the head: 24 crystals were implanted in the brain, and 8 were fixed to the inner skull. A dynamic rotation was then applied to the head using a closed-loop controlled test device. Four pulses with different severity level were applied about three orthogonal anatomical axes of rotation. A repeated test of the highest severity rotation was conducted in each axes to assess repeatability. All tests were completed within 56 hours post-mortem. Overall, the combined experimental and sonomicrometry methods were demonstrated to reliably and repeatedly capture three-dimensional dynamic deformation of an intact human brain. These methods provide a framework for using sonomicrometry to acquire multidimensional experimental data required for FE model development and validation, and will lend insight into the deformations sustained by the brain during impact.

  18. Central surface curvatures of postmortem- extracted intact human crystalline lenses: implications for understanding the mechanism of accommodation.

    Science.gov (United States)

    Schachar, Ronald A

    2004-09-01

    To measure the radii of curvature of postmortem, whole, encapsulated human crystalline lenses, free of all zonular attachments, and to calculate their corresponding optical powers. Experimental study. Thirty human crystalline lenses from donors with a mean age of 33.6+/-14.4 years. Intact clear human crystalline lenses were obtained within an average of 21 hours of death. The lenses were removed from the eye by the contributing eye bank and shipped in Optisol-GS, a physiologic preservative storage medium. These lenses, with intact capsules, were freed of all zonular attachments. The lenses were stored at 7 degrees C and were maintained in the same storage medium during the period that they were held for evaluation. Using a portable Keratron Scout corneal topographer (Eyequip, Ponte Vedra Beach, FL) fixed to an optical bench, the radii of curvatures of the anterior and posterior surfaces of the crystalline lens were measured daily for 10 days after receipt of the tissue. The capsules of the crystalline lenses remained intact, and the lenses were clear throughout the study. Measurements were made at room temperature after removing the lens from storage. Eight repetitions of the topography were made from each surface on each day to determine the accuracy and stability of the measurement. Profile photographs were taken daily to establish the central crystalline lens thickness. The corresponding optical power of each physiologically maintained crystalline lens was calculated. The main outcome measures were the central anterior radius of curvature, the central posterior radius of curvature, the central thickness of each crystalline lens, and the amount of change in these parameters over 10 days. The means +/- standard deviations of the central anterior and posterior radii of curvatures of the 30 adult lenses were 10.5+/-0.6 mm and 7.1+/-1.0 mm, respectively. The mean +/- standard deviation of the central thickness, as measured from profile photographs, was 3.9+/-0.5 mm

  19. Correlation of in vivo neuroimaging abnormalities with postmortem human immunodeficiency virus encephalitis and dendritic loss

    DEFF Research Database (Denmark)

    Archibald, Sarah L.; Masliah, Eliezer; Fennema-Notestine, Christine

    2004-01-01

    BACKGROUND: In the absence of significant opportunistic infection, the most common alterations on neuroimaging in the brains of patients with AIDS include enlarged cerebrospinal fluid spaces, white-matter loss, volume loss in striatal structures, and white-matter signal abnormalities. Although pr...

  20. Cyclic AMP response element-binding protein in post-mortem brain of teenage suicide victims: specific decrease in the prefrontal cortex but not the hippocampus.

    Science.gov (United States)

    Pandey, Ghanshyam N; Dwivedi, Yogesh; Ren, Xinguo; Rizavi, Hooriyah S; Roberts, Rosalinda C; Conley, Robert R

    2007-10-01

    Abnormalities in both adenylyl cyclase (AC) and phosphoinositide (PI) signalling systems have been observed in the post-mortem brain of suicide victims. Cyclic AMP response element-binding protein (CREB) is a transcription factor that is activated by phosphorylating enzymes such as protein kinase A (PKA) and protein kinase C (PKC), which suggests that both AC and PI signalling systems converge at the level of CREB. CREB is involved in the transcription of many neuronally expressed genes that have been implicated in the pathophysiology of depression and suicide. Since we observed abnormalities of both PKA and PKC in the post-mortem brain of teenage suicide victims, we examined if these abnormalities are also associated with abnormalities of CREB, which is activated by these phosphorylating enzymes. We determined CRE-DNA binding using the gel shift assay, as well as protein expression of CREB using the Western blot technique, and the mRNA expression of CREB using a quantitative reverse transcriptase-polymerase chain reaction (RT-PCR) technique in the prefrontal cortex (PFC), and hippocampus obtained from 17 teenage suicide victims and 17 matched normal control subjects. We observed that the CRE-DNA binding and the protein expression of CREB were significantly decreased in the PFC of teenage suicide victims compared with controls. There was also a significant decrease in mRNA expression of CREB in the PFC of teenage suicide victims compared with control subjects. However, there were no significant differences in CRE-DNA binding or the protein and mRNA expression of CREB in the hippocampus of teenage suicide victims compared with control subjects. These results suggest that the abnormalities of PKA, and of PKC, observed in teenage suicide victims are also associated with abnormalities of the transcription factor CREB, and that this may also cause alterations of important neuronally expressed genes, and provide further support of the signal transduction of abnormalities

  1. Mindboggling morphometry of human brains

    Science.gov (United States)

    Bao, Forrest S.; Giard, Joachim; Stavsky, Eliezer; Lee, Noah; Rossa, Brian; Reuter, Martin; Chaibub Neto, Elias

    2017-01-01

    Mindboggle (http://mindboggle.info) is an open source brain morphometry platform that takes in preprocessed T1-weighted MRI data and outputs volume, surface, and tabular data containing label, feature, and shape information for further analysis. In this article, we document the software and demonstrate its use in studies of shape variation in healthy and diseased humans. The number of different shape measures and the size of the populations make this the largest and most detailed shape analysis of human brains ever conducted. Brain image morphometry shows great potential for providing much-needed biological markers for diagnosing, tracking, and predicting progression of mental health disorders. Very few software algorithms provide more than measures of volume and cortical thickness, while more subtle shape measures may provide more sensitive and specific biomarkers. Mindboggle computes a variety of (primarily surface-based) shapes: area, volume, thickness, curvature, depth, Laplace-Beltrami spectra, Zernike moments, etc. We evaluate Mindboggle’s algorithms using the largest set of manually labeled, publicly available brain images in the world and compare them against state-of-the-art algorithms where they exist. All data, code, and results of these evaluations are publicly available. PMID:28231282

  2. Neurofibrillary tangle pathology and Braak staging in chronic epilepsy in relation to traumatic brain injury and hippocampal sclerosis: a post-mortem study

    Science.gov (United States)

    Liu, Joan Y.W.; Thompson, Pam; Phadke, Rahul; Narkiewicz, Marta; Martinian, Lillian; Marsdon, Derek; Koepp, Matthias; Caboclo, Luis; Catarino, Claudia B.; Sisodiya, Sanjay M.

    2011-01-01

    The long-term pathological effects of chronic epilepsy on normal brain ageing are unknown. Previous clinical and epidemiological studies show progressive cognitive decline in subsets of patients and an increased prevalence of Alzheimer's disease in epilepsy. In a post-mortem series of 138 patients with long-term, mainly drug-resistant epilepsy, we carried out Braak staging for Alzheimer's disease neurofibrillary pathology using tau protein immunohistochemistry. The stages were compared with clinicopathological factors, including seizure history and presence of old traumatic brain injury. Overall, 31% of cases were Braak Stage 0, 36% Stage I/II, 31% Stage III/IV and 2% Stage V/VI. The mean age at death was 56.5 years and correlated with Braak stage (P epilepsy series (P type (generalized or complex partial), seizure frequency, age of onset and duration of epilepsy with Braak stage although higher Braak stages were noted with focal more than with generalized epilepsy syndromes (P epilepsy although progression to high Braak stages was infrequent. Traumatic brain injury, but not seizures, was associated with tau protein accumulation in this series. It is likely that Alzheimer's disease pathology is not the sole explanation for cognitive decline associated with epilepsy. PMID:21903728

  3. Abnormal brain iron homeostasis in human and animal prion disorders.

    Directory of Open Access Journals (Sweden)

    Ajay Singh

    2009-03-01

    Full Text Available Neurotoxicity in all prion disorders is believed to result from the accumulation of PrP-scrapie (PrP(Sc, a beta-sheet rich isoform of a normal cell-surface glycoprotein, the prion protein (PrP(C. Limited reports suggest imbalance of brain iron homeostasis as a significant associated cause of neurotoxicity in prion-infected cell and mouse models. However, systematic studies on the generality of this phenomenon and the underlying mechanism(s leading to iron dyshomeostasis in diseased brains are lacking. In this report, we demonstrate that prion disease-affected human, hamster, and mouse brains show increased total and redox-active Fe (II iron, and a paradoxical increase in major iron uptake proteins transferrin (Tf and transferrin receptor (TfR at the end stage of disease. Furthermore, examination of scrapie-inoculated hamster brains at different timepoints following infection shows increased levels of Tf with time, suggesting increasing iron deficiency with disease progression. Sporadic Creutzfeldt-Jakob disease (sCJD-affected human brains show a similar increase in total iron and a direct correlation between PrP and Tf levels, implicating PrP(Sc as the underlying cause of iron deficiency. Increased binding of Tf to the cerebellar Purkinje cell neurons of sCJD brains further indicates upregulation of TfR and a phenotype of neuronal iron deficiency in diseased brains despite increased iron levels. The likely cause of this phenotype is sequestration of iron in brain ferritin that becomes detergent-insoluble in PrP(Sc-infected cell lines and sCJD brain homogenates. These results suggest that sequestration of iron in PrP(Sc-ferritin complexes induces a state of iron bio-insufficiency in prion disease-affected brains, resulting in increased uptake and a state of iron dyshomeostasis. An additional unexpected observation is the resistance of Tf to digestion by proteinase-K, providing a reliable marker for iron levels in postmortem human brains. These

  4. Brain development in rodents and humans: Identifying benchmarks of maturation and vulnerability to injury across species

    Science.gov (United States)

    Semple, Bridgette D.; Blomgren, Klas; Gimlin, Kayleen; Ferriero, Donna M.; Noble-Haeusslein, Linda J.

    2013-01-01

    Hypoxic-ischemic and traumatic brain injuries are leading causes of long-term mortality and disability in infants and children. Although several preclinical models using rodents of different ages have been developed, species differences in the timing of key brain maturation events can render comparisons of vulnerability and regenerative capacities difficult to interpret. Traditional models of developmental brain injury have utilized rodents at postnatal day 7–10 as being roughly equivalent to a term human infant, based historically on the measurement of post-mortem brain weights during the 1970s. Here we will examine fundamental brain development processes that occur in both rodents and humans, to delineate a comparable time course of postnatal brain development across species. We consider the timing of neurogenesis, synaptogenesis, gliogenesis, oligodendrocyte maturation and age-dependent behaviors that coincide with developmentally regulated molecular and biochemical changes. In general, while the time scale is considerably different, the sequence of key events in brain maturation is largely consistent between humans and rodents. Further, there are distinct parallels in regional vulnerability as well as functional consequences in response to brain injuries. With a focus on developmental hypoxicischemic encephalopathy and traumatic brain injury, this review offers guidelines for researchers when considering the most appropriate rodent age for the developmental stage or process of interest to approximate human brain development. PMID:23583307

  5. Radiological-Pathological Correlations Following Blast-Related Traumatic Brain Injury in the Whole Human Brain Using ex Vivo Diffusion Tensor Imaging

    Science.gov (United States)

    2014-01-01

    injuries caused by non-blast related trauma (e.g. falls, motor vehicle accidents, etc.), post-mortem pathological analyses have revealed that...part of these advances is the use of high resolution imaging of blocks of human brain at 4.7 Tesla . This high resolution imaging has allowed...to noise Stereological methods: StereoInvestigator software coupled to a motorized stage on a Nikon 80i upright microscope. All tissue

  6. Are polymegethism, pleomorphism, and "poor swelling" valid discard parameters in immediate postmortem evaluation of human donor corneal endothelium?

    Science.gov (United States)

    Bruinsma, Marieke; Lie, Jessica T; Groeneveld-van Beek, Esther A; Liarakos, Vasilis S; van der Wees, Jacqueline; Melles, Gerrit R J

    2013-03-01

    To study the validity of endothelial polymegethism, pleomorphism, and "poor swelling" as tissue discard parameters in the immediate postmortem evaluation of human donor corneal endothelium. We retrospectively evaluated the quality of the endothelium at first and second evaluations for all processed corneas exhibiting moderate polymegethism, pleomorphism, or "poor swelling" in our eye bank over a 5-year period. Out of 2008 eyes qualifying for our study, 422 corneas (21%) showed polymegethism, pleomorphism, or poor swelling at the first tissue evaluation immediately after excision of the corneoscleral button. In 363 (86%) of these corneas, a normal endothelial mosaic was observed at the second tissue evaluation after 7 to 21 days of organ culture, whereas only 59 (14%) still showed persistent polymegethism, pleomorphism, or "poor swelling" at that time point. A recovery of normal endothelial cell mosaic and "normal swelling" at the second evaluation suggests that cellular contour parameters do not relate to tissue viability, but rather to a cellular stress reaction. If so, the validity of endothelial cellular contour morphology as an early parameter in assessing the suitability of a donor cornea for transplantation may be reconsidered.

  7. Sexual differences of human brain

    Directory of Open Access Journals (Sweden)

    Masoud Pezeshki Rad

    2014-04-01

    Full Text Available During the last decades there has been an increasing interest in studying the differences between males and females. These differences extend from behavioral to cognitive to micro- and macro- neuro-anatomical aspects of human biology. There have been many methods to evaluate these differences and explain their determinants. The most studied cause of this dimorphism is the prenatal sex hormones and their organizational effect on brain and behavior. However, there have been new and recent attentions to hormone's activational influences in puberty and also the effects of genomic imprinting. In this paper, we reviewed the sex differences of brain, the evidences for possible determinants of these differences and also the methods that have been used to discover them. We reviewed the most conspicuous findings with specific attention to macro-anatomical differences based on Magnetic Resonance Imaging (MRI data. We finally reviewed the findings and the many opportunities for future studies.

  8. Post-mortem whole-body magnetic resonance imaging of human fetuses: a comparison of 3-T vs. 1.5-T MR imaging with classical autopsy.

    Science.gov (United States)

    Kang, Xin; Cannie, Mieke M; Arthurs, Owen J; Segers, Valerie; Fourneau, Catherine; Bevilacqua, Elisa; Cos Sanchez, Teresa; Sebire, Neil J; Jani, Jacques C

    2017-08-01

    To prospectively compare diagnostic accuracy of fetal post-mortem whole-body MRI at 3-T vs. 1.5-T. Between 2012 and 2015, post-mortem MRI at 1.5-T and 3-T was performed in fetuses after miscarriage/stillbirth or termination. Clinical MRI diagnoses were assessed using a confidence diagnostic score and compared with classical autopsy to derive a diagnostic error score. The relation of diagnostic error for each organ group with gestational age was calculated and 1.5-T with 3-T was compared with accuracy analysis. 135 fetuses at 12-41 weeks underwent post-mortem MRI (followed by conventional autopsy in 92 fetuses). For all organ groups except the brain, and for both modalities, the diagnostic error decreased with gestation (P autopsy than 1.5-T MRI, especially for the thorax, heart and abdomen in fetuses autopsy increases with 3-T. • PM-MRI using 3-T is particularly interesting for thoracic and abdominal organs. • PM-MRI using 3-T is particularly interesting for fetuses < 20 weeks' gestation.

  9. Lack of infection with XMRV or other MLV-related viruses in blood, post-mortem brains and paternal gametes of autistic individuals.

    Directory of Open Access Journals (Sweden)

    Carla Lintas

    Full Text Available BACKGROUND: Autistic spectrum disorder (ASD is characterized by impaired language, communication and social skills, as well as by repetitive and stereotypic patterns of behavior. Many autistic subjects display a dysregulation of the immune system which is compatible with an unresolved viral infection with prenatal onset, potentially due to vertical viral transmission. Recently, the xenotropic murine leukemia virus-related virus (XMRV has been implicated in chronic fatigue syndrome (CFS and in prostate cancer by several, though not all studies. METHODOLOGY/PRINCIPAL FINDINGS: We assessed whether XMRV or other murine leukemia virus (MLV-related viruses are involved in autistic disorder. Using nested PCR targeted to gag genomic sequences, we screened DNA samples from: (i peripheral blood of 102 ASD patients and 97 controls, (ii post-mortem brain samples of 20 ASD patients and 17 sex- and age-matched controls, (iii semen samples of 11 fathers of ASD children, 25 infertile individuals and 7 fertile controls. No XMRV gag DNA sequences were detected, whereas peripheral blood samples of 3/97 (3.1% controls were positive for MLV. CONCLUSIONS| SIGNIFICANCE: No MLV-related virus was detected in blood, brain, and semen samples of ASD patients or fathers. Hence infection with XMRV or other MLV-related viruses is unlikely to contribute to autism pathogenesis.

  10. Characteristics of human infant primary fibroblast cultures from Achilles tendons removed post-mortem

    DEFF Research Database (Denmark)

    Rohde, Marianne Cathrine; Corydon, Thomas Juhl; Hansen, Jakob

    2014-01-01

    Primary cell cultures were investigated as a tool for molecular diagnostics in a forensic setting. Fibroblast cultures had been established from human Achilles tendon resected at autopsies, from cases of sudden infant death syndrome and control infants who died in traumatic events (n=41). After...

  11. Characteristics of the number of odontoblasts in human dental pulp post-mortem.

    Science.gov (United States)

    Vavpotic, Marko; Turk, Tomaz; Martincic, Draga Stiblar; Balazic, Joze

    2009-12-15

    Estimation of the time since death is important in forensic medicine, and so far not much is known in employing dental pulp for such purposes. The tooth organ is the hardest organ in the human body, with a loose connective tissue of dental pulp situated within a rigid encasement of mineralized surrounding tissues. Human material was obtained from 31 corpses of people who died in car and train accidents and had healthy oral statuses. Samples were divided into two groups at different environmental temperatures. During the autopsy, the jaws were resected to keep teeth in situ, and every day one tooth was extracted. After decalcification, serial thin sections stained with hematoxylin and eosin were cut. Odontoblasts in the dental pulp were counted and data analysed. Statistical analysis showed that the number of odontoblasts drops during the time after death, and no odontoblasts remain in the pulp after 5 days.

  12. Region-specific alterations in the corticotropin-releasing factor and glucocorticoid receptors in the postmortem brain of suicide victims

    OpenAIRE

    Ghanshyam N. Pandey

    2012-01-01

    Rationale : Abnormalities of hypothalamic–pituitary–adrenal (HPA) axis in depression and suicide are among the most consistent findings in biological psychiatry. However, the specific molecular mechanism associated with HPA axis abnormality in the brain of depressed or suicidal subjects is not clear. It is believed that abnormal HPA axis is caused by increased levels of corticotropin-releasing factor (CRF) and decreased levels of glucocorticoid receptor (GR) in the brain of depr...

  13. Acinar autolysis and mucous extravasation in human sublingual glands: a microscopic postmortem study

    Directory of Open Access Journals (Sweden)

    Luciana Reis AZEVEDO-ALANIS

    2015-10-01

    Full Text Available Although some morphological investigations on aged human sublingual glands (HSG found eventual phenomena identified as autolysis and mucous extravasation, the exact meaning of these findings has not been elucidated.Objective The aim of this work is to investigate whether acinar autolysis and mucous extravasation are related to the aging process in human sublingual glands. We also speculate if autolytic changes may assist forensic pathologists in determining time of death.Material and Methods 186 cadavers’ glands were allocated to age groups: I (0–30 years; II (31–60, and III (61–90. Time and mode of death were also recorded. Acinar autolysis and mucous extravasation were classified as present or absent. Ultrastructural analysis was performed using transmission electron microscopy (TEM. Data were compared using Mann-Whitney U, Spearman’s correlation coefficient, Kruskal-Wallis, and Dunn tests (p<0.05.Results There was correlation between age and acinar autolysis (r=0.38; p=0.0001. However, there was no correlation between autolysis and time of death. No differences were observed between genders. TEM showed mucous and serous cells presenting nuclear and membrane alterations and mucous cells were more susceptible to autolysis.Conclusion Acinar autolysis occurred in all age groups and increased with age while mucous extravasation was rarely found. Both findings are independent. Autolysis degrees in HSG could not be used to determine time of death.

  14. Brain mechanisms underlying human communication

    Directory of Open Access Journals (Sweden)

    Matthijs L Noordzij

    2009-07-01

    Full Text Available Human communication has been described as involving the coding-decoding of a conventional symbol system, which could be supported by parts of the human motor system (i.e. the “mirror neurons system”. However, this view does not explain how these conventions could develop in the first place. Here we target the neglected but crucial issue of how people organize their non-verbal behavior to communicate a given intention without pre-established conventions. We have measured behavioral and brain responses in pairs of subjects during communicative exchanges occurring in a real, interactive, on-line social context. In two fMRI studies, we found robust evidence that planning new communicative actions (by a sender and recognizing the communicative intention of the same actions (by a receiver relied on spatially overlapping portions of their brains (the right posterior superior temporal sulcus. The response of this region was lateralized to the right hemisphere, modulated by the ambiguity in meaning of the communicative acts, but not by their sensorimotor complexity. These results indicate that the sender of a communicative signal uses his own intention recognition system to make a prediction of the intention recognition performed by the receiver. This finding supports the notion that our communicative abilities are distinct from both sensorimotor processes and language abilities.

  15. Automating cell detection and classification in human brain fluorescent microscopy images using dictionary learning and sparse coding.

    Science.gov (United States)

    Alegro, Maryana; Theofilas, Panagiotis; Nguy, Austin; Castruita, Patricia A; Seeley, William; Heinsen, Helmut; Ushizima, Daniela M; Grinberg, Lea T

    2017-04-15

    Immunofluorescence (IF) plays a major role in quantifying protein expression in situ and understanding cell function. It is widely applied in assessing disease mechanisms and in drug discovery research. Automation of IF analysis can transform studies using experimental cell models. However, IF analysis of postmortem human tissue relies mostly on manual interaction, often subjected to low-throughput and prone to error, leading to low inter and intra-observer reproducibility. Human postmortem brain samples challenges neuroscientists because of the high level of autofluorescence caused by accumulation of lipofuscin pigment during aging, hindering systematic analyses. We propose a method for automating cell counting and classification in IF microscopy of human postmortem brains. Our algorithm speeds up the quantification task while improving reproducibility. Dictionary learning and sparse coding allow for constructing improved cell representations using IF images. These models are input for detection and segmentation methods. Classification occurs by means of color distances between cells and a learned set. Our method successfully detected and classified cells in 49 human brain images. We evaluated our results regarding true positive, false positive, false negative, precision, recall, false positive rate and F1 score metrics. We also measured user-experience and time saved compared to manual countings. We compared our results to four open-access IF-based cell-counting tools available in the literature. Our method showed improved accuracy for all data samples. The proposed method satisfactorily detects and classifies cells from human postmortem brain IF images, with potential to be generalized for applications in other counting tasks. Copyright © 2017 Elsevier B.V. All rights reserved.

  16. Micro-anatomy of the renal sympathetic nervous system: a human postmortem histologic study.

    Science.gov (United States)

    Atherton, Daniel S; Deep, Nicholas L; Mendelsohn, Farrell O

    2012-07-01

    Hypertension remains an epidemic uncontrolled with pharmacologic therapies. A novel catheter inserted into the renal artery has been shown to lower blood pressure by ablating the renal sympathetic nerves with radiofrequency energy delivered through the arterial wall. We report a histologic study describing the anatomic substrate for this technique, specifically the renal sympathetic nervous system. Histological sections from proximal, middle, and distal renal artery segments from nine renal arteries (five human autopsies) were analyzed. Nerves were manually counted and their distance from the lumen-intima interface was measured using a micrometer. The nerves were then categorized by location into 0.5-mm-wide "rings" that were arranged circumferentially around the renal artery lumen. Of all nerves detected, 1.0% was in the 0-0.5 mm ring, 48.3% were in the 0.5-1.0 mm ring, 25.6% were in the 1.0-1.5 mm ring, 15.5% were in the 1.5-2.0 mm ring, and 9.5% were in the 2.0-2.5 mm ring. Beyond 0.5 mm, the proportion of nerves tended to decrease as the distance from the lumen increased. Totally, 90.5% of all nerves in this study existed within 2.0 mm of the renal artery lumen. Additionally, the number of nerves tended to increase along the length of the artery from proximal to distal segments (proximal = 216; middle = 323; distal = 417). In conclusion, our analysis indicates that a great proportion of renal sympathetic nerves have close proximity to the lumen-intima interface and should thus be accessible via renal artery interventional approaches such as catheter ablation. This data provides important anatomic information for the development of ablation and other type devices for renal sympathetic denervation. © 2011 Wiley Periodicals, Inc.

  17. Comparison study of two different procedures for the determination of drugs of abuse in postmortem brain samples

    DEFF Research Database (Denmark)

    Holm, Karen Marie Dollerup; Reiter, Birgit; Skov, Louise

    2014-01-01

    The aim of this study was to compare two routine solid phase extraction methods for the analysis of body-fluids and tissue samples; a routine method developed in Vienna for tissue samples compared to a routine method developed in Copenhagen for blood. Our approach was to simply exchange the matri......, diazepam and 7-aminoflunitrazepam) in 19 brain homogenates of authentic cases were conducted....

  18. Brain evolution and human neuropsychology: the inferential brain hypothesis.

    Science.gov (United States)

    Koscik, Timothy R; Tranel, Daniel

    2012-05-01

    Collaboration between human neuropsychology and comparative neuroscience has generated invaluable contributions to our understanding of human brain evolution and function. Further cross-talk between these disciplines has the potential to continue to revolutionize these fields. Modern neuroimaging methods could be applied in a comparative context, yielding exciting new data with the potential of providing insight into brain evolution. Conversely, incorporating an evolutionary base into the theoretical perspectives from which we approach human neuropsychology could lead to novel hypotheses and testable predictions. In the spirit of these objectives, we present here a new theoretical proposal, the Inferential Brain Hypothesis, whereby the human brain is thought to be characterized by a shift from perceptual processing to inferential computation, particularly within the social realm. This shift is believed to be a driving force for the evolution of the large human cortex. (JINS, 2012, 18, 394-401).

  19. Brain Evolution and Human Neuropsychology: The Inferential Brain Hypothesis

    Science.gov (United States)

    Koscik, Timothy R.; Tranel, Daniel

    2013-01-01

    Collaboration between human neuropsychology and comparative neuroscience has generated invaluable contributions to our understanding of human brain evolution and function. Further cross-talk between these disciplines has the potential to continue to revolutionize these fields. Modern neuroimaging methods could be applied in a comparative context, yielding exciting new data with the potential of providing insight into brain evolution. Conversely, incorporating an evolutionary base into the theoretical perspectives from which we approach human neuropsychology could lead to novel hypotheses and testable predictions. In the spirit of these objectives, we present here a new theoretical proposal, the Inferential Brain Hypothesis, whereby the human brain is thought to be characterized by a shift from perceptual processing to inferential computation, particularly within the social realm. This shift is believed to be a driving force for the evolution of the large human cortex. PMID:22459075

  20. Neuronal subtypes and diversity revealed by single-nucleus RNA sequencing of the human brain.

    Science.gov (United States)

    Lake, Blue B; Ai, Rizi; Kaeser, Gwendolyn E; Salathia, Neeraj S; Yung, Yun C; Liu, Rui; Wildberg, Andre; Gao, Derek; Fung, Ho-Lim; Chen, Song; Vijayaraghavan, Raakhee; Wong, Julian; Chen, Allison; Sheng, Xiaoyan; Kaper, Fiona; Shen, Richard; Ronaghi, Mostafa; Fan, Jian-Bing; Wang, Wei; Chun, Jerold; Zhang, Kun

    2016-06-24

    The human brain has enormously complex cellular diversity and connectivities fundamental to our neural functions, yet difficulties in interrogating individual neurons has impeded understanding of the underlying transcriptional landscape. We developed a scalable approach to sequence and quantify RNA molecules in isolated neuronal nuclei from a postmortem brain, generating 3227 sets of single-neuron data from six distinct regions of the cerebral cortex. Using an iterative clustering and classification approach, we identified 16 neuronal subtypes that were further annotated on the basis of known markers and cortical cytoarchitecture. These data demonstrate a robust and scalable method for identifying and categorizing single nuclear transcriptomes, revealing shared genes sufficient to distinguish previously unknown and orthologous neuronal subtypes as well as regional identity and transcriptomic heterogeneity within the human brain. Copyright © 2016, American Association for the Advancement of Science.

  1. Assessing various Infrared (IR) microscopic imaging techniques for post-mortem interval evaluation of human skeletal remains.

    Science.gov (United States)

    Woess, Claudia; Unterberger, Seraphin Hubert; Roider, Clemens; Ritsch-Marte, Monika; Pemberger, Nadin; Cemper-Kiesslich, Jan; Hatzer-Grubwieser, Petra; Parson, Walther; Pallua, Johannes Dominikus

    2017-01-01

    Due to the influence of many environmental processes, a precise determination of the post-mortem interval (PMI) of skeletal remains is known to be very complicated. Although methods for the investigation of the PMI exist, there still remains much room for improvement. In this study the applicability of infrared (IR) microscopic imaging techniques such as reflection-, ATR- and Raman- microscopic imaging for the estimation of the PMI of human skeletal remains was tested. PMI specific features were identified and visualized by overlaying IR imaging data with morphological tissue structures obtained using light microscopy to differentiate between forensic and archaeological bone samples. ATR and reflection spectra revealed that a more prominent peak at 1042 cm-1 (an indicator for bone mineralization) was observable in archeological bone material when compared with forensic samples. Moreover, in the case of the archaeological bone material, a reduction in the levels of phospholipids, proteins, nucleic acid sugars, complex carbohydrates as well as amorphous or fully hydrated sugars was detectable at (reciprocal wavelengths/energies) between 3000 cm-1 to 2800 cm-1. Raman spectra illustrated a similar picture with less ν2PO43-at 450 cm-1 and ν4PO43- from 590 cm-1 to 584 cm-1, amide III at 1272 cm-1 and protein CH2 deformation at 1446 cm-1 in archeological bone material/samples/sources. A semi-quantitative determination of various distributions of biomolecules by chemi-maps of reflection- and ATR- methods revealed that there were less carbohydrates and complex carbohydrates as well as amorphous or fully hydrated sugars in archaeological samples compared with forensic bone samples. Raman- microscopic imaging data showed a reduction in B-type carbonate and protein α-helices after a PMI of 3 years. The calculated mineral content ratio and the organic to mineral ratio displayed that the mineral content ratio increases, while the organic to mineral ratio decreases with time

  2. Presence of D4 dopamine receptors in human prefrontal cortex: a postmortem study Presença de receptores dopaminérgicos D4 em córtex cerebral humano: um estudo post-mortem

    Directory of Open Access Journals (Sweden)

    Donatella Marazziti

    2007-06-01

    Full Text Available OBJECTIVE: The aim of our study was to explore the presence and the distribution of D4 dopamine receptors in postmortem human prefrontal cortex, by means of the binding of [³H]YM-09151-2, an antagonist that has equal affinity for D2, D3 and D4 receptors. It was therefore necessary to devise a unique assay method in order to distinguish and detect the D4 component. METHOD: Frontal cortex samples were harvested postmortem, during autopsy sessions, from 5 subjects. In the first assay, tissue homogenates were incubated with increasing concentrations of [³H]YM-09151-2, whereas L-745870, which has a high affinity for D4 and a low affinity for D2/D3 receptors, was used as the displacer. In the second assay, raclopride, which has a high affinity for D2/D3 receptors and a low affinity for D4 receptors, was used to block D2/D3. The L-745870 (500 nM was added to both assays in order to determine the nonspecific binding. RESULTS: Our experiments revealed the presence of specific and saturable binding of [³H]YM-09151-2. The blockade of D2 and D3 receptors with raclopride ensured that the D4 receptors were labeled. The mean maximum binding capacity was 88 ± 25 fmol/mg protein, and the dissociation constant was 0.8 ± 0.4 nM. DISCUSSION AND CONCLUSIONS: Our findings, although not conclusive, suggest that the density of D4 receptors is low in the human prefrontal cortex.OBJETIVO: O objetivo deste estudo foi quantificar a presença e a distribuição de receptores dopaminérgicos do tipo 4 (D4 no córtex cerebral humano em amostras post-mortem através do bloqueio com ³H-YM-09151-2 - um antagonista com afinidade equivalente pelos receptores D2, D3 e D4 - e do desenvolvimento de um método para a detecção específica do componente D4. MÉTODO: Foram obtidas amostras de córtex cerebral de cinco cadáveres. Em um primeiro ensaio, os homogeneizados de tecido cerebral foram incubados em concentrações crescentes de ³H-YM-09151-2, enquanto que o L-745

  3. Computational Intelligence in a Human Brain Model

    Directory of Open Access Journals (Sweden)

    Viorel Gaftea

    2016-06-01

    Full Text Available This paper focuses on the current trends in brain research domain and the current stage of development of research for software and hardware solutions, communication capabilities between: human beings and machines, new technologies, nano-science and Internet of Things (IoT devices. The proposed model for Human Brain assumes main similitude between human intelligence and the chess game thinking process. Tactical & strategic reasoning and the need to follow the rules of the chess game, all are very similar with the activities of the human brain. The main objective for a living being and the chess game player are the same: securing a position, surviving and eliminating the adversaries. The brain resolves these goals, and more, the being movement, actions and speech are sustained by the vital five senses and equilibrium. The chess game strategy helps us understand the human brain better and easier replicate in the proposed ‘Software and Hardware’ SAH Model.

  4. Evidence for the recruitment of autophagic vesicles in human brain after stroke.

    Science.gov (United States)

    Frugier, Tony; Taylor, Juliet M; McLean, Catriona; Bye, Nicole; Beart, Philip M; Devenish, Rodney J; Crack, Peter J

    2016-06-01

    Autophagy is a homeostatic process for recycling proteins and organelles that is increasingly being proposed as a therapeutic target for acute and chronic neurodegenerative diseases, including stroke. Confirmation that autophagy is present in the human brain after stroke is imperative before prospective therapies can begin the translational process into clinical trials. Our current study using human post-mortem tissue observed an increase in staining in microtubule-associated protein 1 light chain 3 (LC3), sequestosome 1 (SQSTM1; also known as p62) and the increased appearance of autophagic vesicles after stroke. These data confirm that alterations in autophagy take place in the human brain after stroke and suggest that targeting autophagic processes after stroke may have clinical significance. Copyright © 2016 Elsevier Ltd. All rights reserved.

  5. Male microchimerism in the human female brain.

    Directory of Open Access Journals (Sweden)

    William F N Chan

    Full Text Available In humans, naturally acquired microchimerism has been observed in many tissues and organs. Fetal microchimerism, however, has not been investigated in the human brain. Microchimerism of fetal as well as maternal origin has recently been reported in the mouse brain. In this study, we quantified male DNA in the human female brain as a marker for microchimerism of fetal origin (i.e. acquisition of male DNA by a woman while bearing a male fetus. Targeting the Y-chromosome-specific DYS14 gene, we performed real-time quantitative PCR in autopsied brain from women without clinical or pathologic evidence of neurologic disease (n=26, or women who had Alzheimer's disease (n=33. We report that 63% of the females (37 of 59 tested harbored male microchimerism in the brain. Male microchimerism was present in multiple brain regions. Results also suggested lower prevalence (p=0.03 and concentration (p=0.06 of male microchimerism in the brains of women with Alzheimer's disease than the brains of women without neurologic disease. In conclusion, male microchimerism is frequent and widely distributed in the human female brain.

  6. Pathological Tau Strains from Human Brains Recapitulate the Diversity of Tauopathies in Nontransgenic Mouse Brain.

    Science.gov (United States)

    Narasimhan, Sneha; Guo, Jing L; Changolkar, Lakshmi; Stieber, Anna; McBride, Jennifer D; Silva, Luisa V; He, Zhuohao; Zhang, Bin; Gathagan, Ronald J; Trojanowski, John Q; Lee, Virginia M Y

    2017-11-22

    Pathological tau aggregates occur in Alzheimer's disease (AD) and other neurodegenerative tauopathies. It is not clearly understood why tauopathies vary greatly in the neuroanatomical and histopathological patterns of tau aggregation, which contribute to clinical heterogeneity in these disorders. Recent studies have shown that tau aggregates may form distinct structural conformations, known as tau strains. Here, we developed a novel model to test the hypothesis that cell-to-cell transmission of different tau strains occurs in nontransgenic (non-Tg) mice, and to investigate whether there are strain-specific differences in the pattern of tau transmission. By injecting pathological tau extracted from postmortem brains of AD (AD-tau), progressive supranuclear palsy (PSP-tau), and corticobasal degeneration (CBD-tau) patients into different brain regions of female non-Tg mice, we demonstrated the induction and propagation of endogenous mouse tau aggregates. Specifically, we identified differences in tau strain potency between AD-tau, CBD-tau, and PSP-tau in non-Tg mice. Moreover, differences in cell-type specificity of tau aggregate transmission were observed between tau strains such that only PSP-tau and CBD-tau strains induce astroglial and oligodendroglial tau inclusions, recapitulating the diversity of neuropathology in human tauopathies. Furthermore, we demonstrated that the neuronal connectome, but not the tau strain, determines which brain regions develop tau pathology. Finally, CBD-tau- and PSP-tau-injected mice showed spatiotemporal transmission of glial tau pathology, suggesting glial tau transmission contributes to the progression of tauopathies. Together, our data suggest that different tau strains determine seeding potency and cell-type specificity of tau aggregation that underlie the diversity of human tauopathies. SIGNIFICANCE STATEMENT Tauopathies show great clinical and neuropathological heterogeneity, despite the fact that tau aggregates in each disease

  7. Abnormal activity of the MAPK- and cAMP-associated signaling pathways in frontal cortical areas in postmortem brain in schizophrenia.

    Science.gov (United States)

    Funk, Adam J; McCullumsmith, Robert E; Haroutunian, Vahram; Meador-Woodruff, James H

    2012-03-01

    Recent evidence suggests that schizophrenia may result from alterations of integration of signaling mediated by multiple neurotransmitter systems. Abnormalities of associated intracellular signaling pathways may contribute to the pathophysiology of schizophrenia. Proteins and phospho-proteins comprising mitogen activated protein kinase (MAPK) and 3'-5'-cyclic adenosine monophosphate (cAMP)-associated signaling pathways may be abnormally expressed in the anterior cingulate (ACC) and dorsolateral prefrontal cortex (DLPFC) in schizophrenia. Using western blot analysis we examined proteins of the MAPK- and cAMP-associated pathways in these two brain regions. Postmortem samples were used from a well-characterized collection of elderly patients with schizophrenia (ACC=36, DLPFC=35) and a comparison (ACC=33, DLPFC=31) group. Near-infrared intensity of IR-dye labeled secondary antisera bound to targeted proteins of the MAPK- and cAMP-associated signaling pathways was measured using LiCor Odyssey imaging system. We found decreased expression of Rap2, JNK1, JNK2, PSD-95, and decreased phosphorylation of JNK1/2 at T183/Y185 and PSD-95 at S295 in the ACC in schizophrenia. In the DLPFC, we found increased expression of Rack1, Fyn, Cdk5, and increased phosphorylation of PSD-95 at S295 and NR2B at Y1336. MAPK- and cAMP-associated molecules constitute ubiquitous intracellular signaling pathways that integrate extracellular stimuli, modify receptor expression and function, and regulate cell survival and neuroplasticity. These data suggest abnormal activity of the MAPK- and cAMP-associated pathways in frontal cortical areas in schizophrenia. These alterations may underlie the hypothesized hypoglutamatergic function in this illness. Together with previous findings, these data suggest that abnormalities of intracellular signaling pathways may contribute to the pathophysiology of schizophrenia.

  8. Characterisation of new monoclonal antibodies reacting with prions from both human and animal brain tissues

    DEFF Research Database (Denmark)

    Cordes, H.; Bergstrom, A.L.; Ohm, J.

    2008-01-01

    Post-mortem diagnosis of transmissible spongiform encephalopathies (prion diseases) is primarily based on the detection of a protease resistant, misfolded disease associated isoform (PrP(Sc)) of the prion protein (PrP(C)) on neuronal cells. These methods depend on antibodies directed against Pr......-type mice and used for western blotting and immunohistochemistry to detect several types of human prion-disease associated PrP(Sc), including sporadic Creutzfeldt-Jakob Disease (CJD) (subtypes MM1 and VV2), familial CJD and Gerstmann-Straussler-Scheinker (GSS) disease PrP(Sc) as well as PrP(Sc) of bovine...... spongiform encephalopathy (bovine brain), scrapie (ovine brain) and experimental scrapie in hamster and in mice. The antibodies were also used for PET-blotting in which PrP(Sc) blotted from brain tissue sections onto a nitrocellulose membrane is visualized with antibodies after protease and denaturant...

  9. Autism counts. Stereological studies on human postmortem brains and a mouse model for autism

    NARCIS (Netherlands)

    van Kooten, I.A.J.

    2008-01-01

    Autism is a neurodevelopmental disorder with a strong genetic component and several known environmental risk factors. Classical neuropathology studies have reported consistent findings in the limbic system, cerebellum and cerebral cortex of patients with autism. However, the neurobiological

  10. Consumption of seaweeds and the human brain

    DEFF Research Database (Denmark)

    Cornish, M. Lynn; Critchley, Alan T.; Mouritsen, Ole G.

    2017-01-01

    highlighting the potential impacts of the consumption of a variety of seaweeds on human brain health and includes theories in relation to the benefits to early Homo sapiens. The emphasis is on a varied diet including macroalgae and the gut/microbe/brain axis, the importance of polyunsaturated fatty acids...

  11. Lactate fuels the human brain during exercise

    NARCIS (Netherlands)

    Quistorff, Bjorn; Secher, Niels H.; van Lieshout, Johannes J.

    2008-01-01

    The human brain releases a small amount of lactate at rest, and even an increase in arterial blood lactate during anesthesia does not provoke a net cerebral lactate uptake. However, during cerebral activation associated with exercise involving a marked increase in plasma lactate, the brain takes up

  12. An introduction to human brain anatomy

    NARCIS (Netherlands)

    Forstmann, B.U.; Keuken, M.C.; Alkemade, A.; Forstmann, B.U.; Wagenmakers, E.-J.

    2015-01-01

    This tutorial chapter provides an overview of the human brain anatomy. Knowledge of brain anatomy is fundamental to our understanding of cognitive processes in health and disease; moreover, anatomical constraints are vital for neurocomputational models and can be important for psychological

  13. Constitutional Aneuploidy in the Normal Human Brain

    National Research Council Canada - National Science Library

    Rehen, Stevens K; Yung, Yun C; McCreight, Matthew P; Kaushal, Dhruv; Yang, Amy H; Almeida, Beatriz S. V; Kingsbury, Marcy A; Cabral, Katia M. S; McConnell, Michael J; Anliker, Brigitte; Fontanoz, Marisa; Chun, Jerold

    2005-01-01

    .... Chromosome 21 aneuploid cells constitute approximately 4% of the estimated one trillion cells in the human brain and include non-neuronal cells and postmitotic neurons identified by the neuronspecific nuclear protein marker...

  14. Brain-derived neurotrophic factor (BDNF) and neurotrophin 3 (NT3) levels in post-mortem brain tissue from patients with depression compared to healthy individuals 

    DEFF Research Database (Denmark)

    Sheldrick, A; Camara, S; Ilieva, M

    2017-01-01

    suggests that antidepressant treatment may improve or normalise cerebral concentrations of neurotrophic factors. Therefore, we examined the concentration of brain-derived neurotrophic factor (BDNF) and neurotrophin 3 (NT3) in different brain regions (cortex, cingulate gyrus, thalamus, hippocampus, putamen...... treatment and overall age 84.3±5 years versus 14 unaffected subjects at age 70.3±13.8. We detected significant elevation of BDNF (parietal cortex) and NT3 (parietal, temporal and occipital cortex, cingulate gyrus, thalamus, putamen and nucleus caudatus regions) in MDD patients who received antidepressant...

  15. 168 sections of a human brain

    OpenAIRE

    Biscotti, Rossella

    2015-01-01

    Tiré du site Internet de Boabooks: "The book displays a close up of a human brain with layers of memory and dreams visualized through a method of psychoanalysis and pharmacological propaganda. It is composed of two scientific researches that investigated the theme of memory and psychoanalysis. The first photos ever realized of sections of the human brain by psychiatric G. Jelgersma at the University of Leiden (1908-1911) are paired with the transcript of narcoanalytic sessions conducted by th...

  16. Analysis of a human brain transcriptome map

    Directory of Open Access Journals (Sweden)

    Greene Jonathan R

    2002-04-01

    Full Text Available Abstract Background Genome wide transcriptome maps can provide tools to identify candidate genes that are over-expressed or silenced in certain disease tissue and increase our understanding of the structure and organization of the genome. Expressed Sequence Tags (ESTs from the public dbEST and proprietary Incyte LifeSeq databases were used to derive a transcript map in conjunction with the working draft assembly of the human genome sequence. Results Examination of ESTs derived from brain tissues (excluding brain tumor tissues suggests that these genes are distributed on chromosomes in a non-random fashion. Some regions on the genome are dense with brain-enriched genes while some regions lack brain-enriched genes, suggesting a significant correlation between distribution of genes along the chromosome and tissue type. ESTs from brain tumor tissues have also been mapped to the human genome working draft. We reveal that some regions enriched in brain genes show a significant decrease in gene expression in brain tumors, and, conversely that some regions lacking in brain genes show an increased level of gene expression in brain tumors. Conclusions This report demonstrates a novel approach for tissue specific transcriptome mapping using EST-based quantitative assessment.

  17. Spatial-temporal transcriptional dynamics of long non-coding RNAs in human brain.

    Science.gov (United States)

    Zhang, Xiao-Qin; Wang, Ze-Lin; Poon, Ming-Wai; Yang, Jian-Hua

    2017-08-15

    The functional architecture of the human brain is greatly determined by the temporal and spatial regulation of the transcription process. However, the spatial and temporal transcriptional landscape of long non-coding RNAs (lncRNAs) during human brain development remains poorly understood. Here, we report the genome-wide lncRNA transcriptional analysis in an extensive series of 1340 post-mortem human brain specimens collected from 16 regions spanning the period from early embryo development to late adulthood. We discovered that lncRNA transcriptome dramatically changed during fetal development, while transited to a surprisingly relatively stable state after birth till the late adulthood. We also discovered that the transcription map of lncRNAs was spatially different, and that this spatial difference was developmentally regulated. Of the 16 brain regions explored (cerebellar cortex, thalamus, striatum, amygdala, hippocampus and 11 neocortex areas), cerebellar cortex showed the most distinct lncRNA expression features from all remaining brain regions throughout the whole developmental period, reflecting its unique developmental and functional features. Furthermore, by characterizing the functional modules and cellular processes of the spatial-temporal dynamic lncRNAs, we found that they were significantly associated with the RNA processing, neuron differentiation and synaptic signal transportation processes. Furthermore, we found that many lncRNAs associated with the neurodegenerative Alzheimer and Parkinson diseases were co-expressed in the fetal development of the human brain, and affected the convergent biological processes. In summary, our study provides a comprehensive map for lncRNA transcription dynamics in human brain development, which might shed light on the understanding of the molecular underpinnings of human brain function and disease. © The Author 2017. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

  18. Topographic distribution of brain iron deposition and small cerebrovascular lesions in amyotrophic lateral sclerosis and in frontotemporal lobar degeneration: a post-mortem 7.0-tesla magnetic resonance imaging study with neuropathological correlates.

    Science.gov (United States)

    De Reuck, Jacques; Devos, David; Moreau, Caroline; Auger, Florent; Durieux, Nicolas; Deramecourt, Vincent; Pasquier, Florence; Maurage, Claude-Alain; Cordonnier, Charlotte; Leys, Didier; Bordet, Regis

    2017-12-01

    Amyotrophic lateral sclerosis (ALS) is associated with frontotemporal lobar degeneration (FTLD) in 15% of the cases. A neuropathological continuity between ALS and FTLD-TDP is suspected. The present post-mortem 7.0-tesla magnetic resonance imaging (MRI) study compares the topographic distribution of iron (Fe) deposition and the incidence of small cerebrovascular lesions in ALS and in FTLD brains. Seventy-eight post-mortem brains underwent 7.0-tesla MRI. The patients consisted of 12 with ALS, 38 with FTLD, and 28 controls. Three ALS brains had minor FTLD features. Three coronal sections of a cerebral hemisphere were submitted to T2 and T2* MRI sequences. The amount of Fe deposition in the deep brain structures and the number of small cerebrovascular lesions was determined in ALS and the subtypes of FTLD compared to control brains, with neuropathological correlates. A significant increase of Fe deposition was observed in the claustrum, caudate nucleus, globus pallidus, thalamus, and subthalamic nucleus of the FTLD-FUS and FTLD-TDP groups, while in the ALS one, the Fe increase was only observed in the caudate and the subthalamic nuclei. White matter changes were only significantly more severe in the FTLD compared to those in ALS and in controls brains. Cortical micro-bleeds were increased in the frontal and temporal lobes of FTLD as well as of ALS brains compared to controls. Cortical micro-infarcts were, on the other hand, more frequent in the control compared to the ALS and FTLD groups. The present study supports the assumption of a neuropathological continuity between ALS and FTLD and illustrates the favourable vascular risk profile in these diseases.

  19. The Human Brain Project: Creating a European Research Infrastructure to Decode the Human Brain.

    Science.gov (United States)

    Amunts, Katrin; Ebell, Christoph; Muller, Jeff; Telefont, Martin; Knoll, Alois; Lippert, Thomas

    2016-11-02

    Decoding the human brain is perhaps the most fascinating scientific challenge in the 21st century. The Human Brain Project (HBP), a 10-year European Flagship, targets the reconstruction of the brain's multi-scale organization. It uses productive loops of experiments, medical, data, data analytics, and simulation on all levels that will eventually bridge the scales. The HBP IT architecture is unique, utilizing cloud-based collaboration and development platforms with databases, workflow systems, petabyte storage, and supercomputers. The HBP is developing toward a European research infrastructure advancing brain research, medicine, and brain-inspired information technology. Copyright © 2016. Published by Elsevier Inc.

  20. The Molecular Basis of Human Brain Evolution.

    Science.gov (United States)

    Enard, Wolfgang

    2016-10-24

    Humans are a remarkable species, especially because of the remarkable properties of their brain. Since the split from the chimpanzee lineage, the human brain has increased three-fold in size and has acquired abilities for vocal learning, language and intense cooperation. To better understand the molecular basis of these changes is of great biological and biomedical interest. However, all the about 16 million fixed genetic changes that occurred during human evolution are fully correlated with all molecular, cellular, anatomical and behavioral changes that occurred during this time. Hence, as humans and chimpanzees cannot be crossed or genetically manipulated, no direct evidence for linking particular genetic and molecular changes to human brain evolution can be obtained. Here, I sketch a framework how indirect evidence can be obtained and review findings related to the molecular basis of human cognition, vocal learning and brain size. In particular, I discuss how a comprehensive comparative approach, leveraging cellular systems and genomic technologies, could inform the evolution of our brain in the future. Copyright © 2016 Elsevier Ltd. All rights reserved.

  1. Segmentation and Visualisation of Human Brain Structures

    OpenAIRE

    Hult, Roger

    2003-01-01

    In this thesis the focus is mainly on the development of segmentation techniques for human brain structures and of the visualisation of such structures. The images of the brain are both anatomical images (magnet resonance imaging (MRI) and autoradigraphy) and functional images that show blood flow (functional magnetic imaging (fMRI), positron emission tomography (PET), and single photon emission tomograpy (SPECT)). When working with anatomical images, the structures segmented are visible as d...

  2. Seasonality in human cognitive brain responses.

    Science.gov (United States)

    Meyer, Christelle; Muto, Vincenzo; Jaspar, Mathieu; Kussé, Caroline; Lambot, Erik; Chellappa, Sarah L; Degueldre, Christian; Balteau, Evelyne; Luxen, André; Middleton, Benita; Archer, Simon N; Collette, Fabienne; Dijk, Derk-Jan; Phillips, Christophe; Maquet, Pierre; Vandewalle, Gilles

    2016-03-15

    Daily variations in the environment have shaped life on Earth, with circadian cycles identified in most living organisms. Likewise, seasons correspond to annual environmental fluctuations to which organisms have adapted. However, little is known about seasonal variations in human brain physiology. We investigated annual rhythms of brain activity in a cross-sectional study of healthy young participants. They were maintained in an environment free of seasonal cues for 4.5 d, after which brain responses were assessed using functional magnetic resonance imaging (fMRI) while they performed two different cognitive tasks. Brain responses to both tasks varied significantly across seasons, but the phase of these annual rhythms was strikingly different, speaking for a complex impact of season on human brain function. For the sustained attention task, the maximum and minimum responses were located around summer and winter solstices, respectively, whereas for the working memory task, maximum and minimum responses were observed around autumn and spring equinoxes. These findings reveal previously unappreciated process-specific seasonality in human cognitive brain function that could contribute to intraindividual cognitive changes at specific times of year and changes in affective control in vulnerable populations.

  3. Magnetic resonance spectroscopy of the human brain

    Science.gov (United States)

    Strózik-Kotlorz, D.

    2014-01-01

    I give a brief description of the magnetic resonance spectroscopy (MRS) in the human brain examinations. MRS allows a noninvasive chemical analysis of the brain using a standard high field MR system. Nowadays, the dominant form of MR brain spectroscopy is proton spectroscopy. Two main techniques of MRS, which utilize the chemical shift of metabolites in the external magnetic field, are SVS (single voxel) and CSI (single slice). The major peaks in the spectrum of a normal brain include NAA, Cr, Cho and m-Ins, which are neuronal, energetic, membrane turnover and glial markers, respectively. In disease, two pathological metabolites can be found in the brain spectra: Lac, which is end product of anaerobic glycolysis and Lip, which is a marker of membrane breakdown, occurring in necrosis. The common way to analyze clinical spectra is to determine metabolite ratios, e.g. NAA/Cr, Cho/Cr, Cho/NAA. This analysis permits a safe and noninvasive examination of the brain tissue as each disease state has its own characteristic spectroscopic image. MRS is a valuable diagnostic tool in such clinical applications as detecting brain tumors and differentiating tumors from inflammatory and infectious processes. Proton MRS is also very helpful in diagnostic of ischemic lesions, Alzheimer's disease and hepatic encephalopathy. The MRS brain spectra should always be correlated with the Magnetic Resonance Imaging (MRI) results and alone cannot make neurological diagnosis.

  4. Brain, Craniofacial, and Dental Lesions of a Free-ranging Gray Wolf (Canis lupus) Implicated in a Human Attack in Minnesota, USA.

    Science.gov (United States)

    Schwabenlander, Marc; Stepaniuk, Kevin; Carstensen, Michelle; Armién, Aníbal G

    2016-01-01

    We describe significant brain, craniofacial, and dental lesions in a free-ranging wolf (Canis lupus) involved in a human attack. On postmortem examination, the wolf presented asymmetric atrophy and bone remodeling affecting the mandible, incisive, maxilla, lacrimal, palatine, frontal, and ethmoid bones. There was an asymmetrical skeletal malocclusion and dental abnormalities including rotated, malpositioned, partially erupted teeth, and an odontogenic cyst associated with an unerupted canine tooth. Brain changes were bilateral loss and atrophy of extensive cortex regions including olfactory bulb, peduncles, and tract, and the frontal lobe. We highlight the relevance of a thorough postmortem examination of wildlife to elucidate disease-based abnormal behavior as the reason for human-animal conflict.

  5. 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.

    2017-01-01

    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 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. PMID:28902174

  6. Exploratory Metabolomic Analyses Reveal Compounds Correlated with Lutein Concentration in Frontal Cortex, Hippocampus, and Occipital Cortex of Human Infant Brain.

    Science.gov (United States)

    Lieblein-Boff, Jacqueline C; Johnson, Elizabeth J; Kennedy, Adam D; Lai, Chron-Si; Kuchan, Matthew J

    2015-01-01

    Lutein is a dietary carotenoid well known for its role as an antioxidant in the macula, and recent reports implicate a role for lutein in cognitive function. Lutein is the dominant carotenoid in both pediatric and geriatric brain tissue. In addition, cognitive function in older adults correlated with macular and postmortem brain lutein concentrations. Furthermore, lutein was found to preferentially accumulate in the infant brain in comparison to other carotenoids that are predominant in diet. While lutein is consistently related to cognitive function, the mechanisms by which lutein may influence cognition are not clear. In an effort to identify potential mechanisms through which lutein might influence neurodevelopment, an exploratory study relating metabolite signatures and lutein was completed. Post-mortem metabolomic analyses were performed on human infant brain tissues in three regions important for learning and memory: the frontal cortex, hippocampus, and occipital cortex. Metabolomic profiles were compared to lutein concentration, and correlations were identified and reported here. A total of 1276 correlations were carried out across all brain regions. Of 427 metabolites analyzed, 257 were metabolites of known identity. Unidentified metabolite correlations (510) were excluded. In addition, moderate correlations with xenobiotic relationships (2) or those driven by single outliers (3) were excluded from further study. Lutein concentrations correlated with lipid pathway metabolites, energy pathway metabolites, brain osmolytes, amino acid neurotransmitters, and the antioxidant homocarnosine. These correlations were often brain region-specific. Revealing relationships between lutein and metabolic pathways may help identify potential candidates on which to complete further analyses and may shed light on important roles of lutein in the human brain during development.

  7. Exploratory Metabolomic Analyses Reveal Compounds Correlated with Lutein Concentration in Frontal Cortex, Hippocampus, and Occipital Cortex of Human Infant Brain.

    Directory of Open Access Journals (Sweden)

    Jacqueline C Lieblein-Boff

    Full Text Available Lutein is a dietary carotenoid well known for its role as an antioxidant in the macula, and recent reports implicate a role for lutein in cognitive function. Lutein is the dominant carotenoid in both pediatric and geriatric brain tissue. In addition, cognitive function in older adults correlated with macular and postmortem brain lutein concentrations. Furthermore, lutein was found to preferentially accumulate in the infant brain in comparison to other carotenoids that are predominant in diet. While lutein is consistently related to cognitive function, the mechanisms by which lutein may influence cognition are not clear. In an effort to identify potential mechanisms through which lutein might influence neurodevelopment, an exploratory study relating metabolite signatures and lutein was completed. Post-mortem metabolomic analyses were performed on human infant brain tissues in three regions important for learning and memory: the frontal cortex, hippocampus, and occipital cortex. Metabolomic profiles were compared to lutein concentration, and correlations were identified and reported here. A total of 1276 correlations were carried out across all brain regions. Of 427 metabolites analyzed, 257 were metabolites of known identity. Unidentified metabolite correlations (510 were excluded. In addition, moderate correlations with xenobiotic relationships (2 or those driven by single outliers (3 were excluded from further study. Lutein concentrations correlated with lipid pathway metabolites, energy pathway metabolites, brain osmolytes, amino acid neurotransmitters, and the antioxidant homocarnosine. These correlations were often brain region-specific. Revealing relationships between lutein and metabolic pathways may help identify potential candidates on which to complete further analyses and may shed light on important roles of lutein in the human brain during development.

  8. Brain activation during human male ejaculation

    NARCIS (Netherlands)

    Holstege, Ger; Georgiadis, Janniko R.; Paans, Anne M.J.; Meiners, Linda C.; Graaf, Ferdinand H.C.E. van der; Reinders, A.A.T.Simone

    2003-01-01

    Brain mechanisms that control human sexual behavior in general, and ejaculation in particular, are poorly understood. We used positron emission tomography to measure increases in regional cerebral blood flow (rCBF) during ejaculation compared with sexual stimulation in heterosexual male volunteers.

  9. Brain activation during human male ejaculation revisited

    NARCIS (Netherlands)

    Georgiadis, Janniko R.; Reinders, A. A. T. Simone; Van der Graaf, Ferdinand H. C. E.; Paans, Anne M. J.; Kortekaas, Rudie

    2007-01-01

    In a prior [O-15]-H2O positron emission tomographic study we reported brain regions involved in human male ejaculation. Here, we used another, more recently acquired data set to evaluate the methodological approach of this previous study, and discovered that part of the reported activation pattern

  10. A High-Resolution In Vivo Atlas of the Human Brain's Serotonin System.

    Science.gov (United States)

    Beliveau, Vincent; Ganz, Melanie; Feng, Ling; Ozenne, Brice; Højgaard, Liselotte; Fisher, Patrick M; Svarer, Claus; Greve, Douglas N; Knudsen, Gitte M

    2017-01-04

    The serotonin (5-hydroxytryptamine, 5-HT) system modulates many important brain functions and is critically involved in many neuropsychiatric disorders. Here, we present a high-resolution, multidimensional, in vivo atlas of four of the human brain's 5-HT receptors (5-HT1A, 5-HT1B, 5-HT2A, and 5-HT4) and the 5-HT transporter (5-HTT). The atlas is created from molecular and structural high-resolution neuroimaging data consisting of positron emission tomography (PET) and magnetic resonance imaging (MRI) scans acquired in a total of 210 healthy individuals. Comparison of the regional PET binding measures with postmortem human brain autoradiography outcomes showed a high correlation for the five 5-HT targets and this enabled us to transform the atlas to represent protein densities (in picomoles per milliliter). We also assessed the regional association between protein concentration and mRNA expression in the human brain by comparing the 5-HT density across the atlas with data from the Allen Human Brain atlas and identified receptor- and transporter-specific associations that show the regional relation between the two measures. Together, these data provide unparalleled insight into the serotonin system of the human brain. We present a high-resolution positron emission tomography (PET)- and magnetic resonance imaging-based human brain atlas of important serotonin receptors and the transporter. The regional PET-derived binding measures correlate strongly with the corresponding autoradiography protein levels. The strong correlation enables the transformation of the PET-derived human brain atlas into a protein density map of the serotonin (5-hydroxytryptamine, 5-HT) system. Next, we compared the regional receptor/transporter protein densities with mRNA levels and uncovered unique associations between protein expression and density at high detail. This new in vivo neuroimaging atlas of the 5-HT system not only provides insight in the human brain's regional protein synthesis

  11. Magnetite pollution nanoparticles in the human brain

    Science.gov (United States)

    Maher, Barbara A.; Ahmed, Imad A. M.; Karloukovski, Vassil; MacLaren, Donald A.; Foulds, Penelope G.; Allsop, David; Mann, David M. A.; Torres-Jardón, Ricardo; Calderon-Garciduenas, Lilian

    2016-09-01

    Biologically formed nanoparticles of the strongly magnetic mineral, magnetite, were first detected in the human brain over 20 y ago [Kirschvink JL, Kobayashi-Kirschvink A, Woodford BJ (1992) Proc Natl Acad Sci USA 89(16):7683-7687]. Magnetite can have potentially large impacts on the brain due to its unique combination of redox activity, surface charge, and strongly magnetic behavior. We used magnetic analyses and electron microscopy to identify the abundant presence in the brain of magnetite nanoparticles that are consistent with high-temperature formation, suggesting, therefore, an external, not internal, source. Comprising a separate nanoparticle population from the euhedral particles ascribed to endogenous sources, these brain magnetites are often found with other transition metal nanoparticles, and they display rounded crystal morphologies and fused surface textures, reflecting crystallization upon cooling from an initially heated, iron-bearing source material. Such high-temperature magnetite nanospheres are ubiquitous and abundant in airborne particulate matter pollution. They arise as combustion-derived, iron-rich particles, often associated with other transition metal particles, which condense and/or oxidize upon airborne release. Those magnetite pollutant particles which are iron-bearing nanoparticles, rather than their soluble compounds, can be transported directly into the brain, where they may pose hazard to human health.

  12. A postmortem study of glycine and its potential precursors in chronic schizophrenics.

    Science.gov (United States)

    Kurumaji, A; Watanabe, A; Kumashiro, S; Semba, J; Toru, M

    1996-09-01

    We have measured the concentrations of glycine and its potential precursors, serine and threonine, in 20 areas of the postmortem brains of chronic schizophrenics and controls using high-performance liquid chromatography by pre-column derivatization with dimethyl-amino-azobenzene sulphonyl chloride. The regional distribution pattern of glycine in the postmortem brains with and without the disease was more similar to that of serine (r = 0.874, P threonine (r = 0.476, P threonine was also observed in the supramarginal cortex and posterior portion of the lateral occipitotemporal cortex of the off-drug group of schizophrenics and in the putamen of all schizophrenics. The highly similar distribution pattern of glycine and serine in the postmortem brains supports the close coupling of synthesis and metabolism between these chemicals in human brains. The increased content of glycine in the orbitofrontal cortex, the reduced level of serine in the putamen and the decrease in threonine in the cerebral cortices, which were prominent in the off-drug schizophrenics, may be involved in the pathophysiology of schizophrenia.

  13. Individual differences in human brain development.

    Science.gov (United States)

    Brown, Timothy T

    2017-01-01

    This article discusses recent scientific advances in the study of individual differences in human brain development. Focusing on structural neuroimaging measures of brain morphology and tissue properties, two kinds of variability are related and explored: differences across individuals of the same age and differences across age as a result of development. A recent multidimensional modeling study is explained, which was able to use brain measures to predict an individual's chronological age within about one year on average, in children, adolescents, and young adults between 3 and 20 years old. These findings reveal great regularity in the sequence of the aggregate brain state across different ages and phases of development, despite the pronounced individual differences people show on any single brain measure at any given age. Future research is suggested, incorporating additional measures of brain activity and function. WIREs Cogn Sci 2017, 8:e1389. doi: 10.1002/wcs.1389 For further resources related to this article, please visit the WIREs website. © 2016 The Authors. WIREs Cognitive Science published by Wiley Periodicals, Inc.

  14. [Evolution of human brain and intelligence].

    Science.gov (United States)

    Lakatos, László; Janka, Zoltán

    2008-07-30

    The biological evolution, including human evolution is mainly driven by environmental changes. Accidental genetic modifications and their innovative results make the successful adaptation possible. As we know the human evolution started 7-8 million years ago in the African savannah, where upright position and bipedalism were significantly advantageous. The main drive of improving manual actions and tool making could be to obtain more food. Our ancestor got more meat due to more successful hunting, resulting in more caloric intake, more protein and essential fatty acid in the meal. The nervous system uses disproportionally high level of energy, so better quality of food was a basic condition for the evolution of huge human brain. The size of human brain was tripled during 3.5 million years, it increased from the average of 450 cm3 of Australopithecinae to the average of 1350 cm3 of Homo sapiens. A genetic change in the system controlling gene expression could happen about 200 000 years ago, which influenced the development of nervous system, the sensorimotor function and learning ability for motor processes. The appearance and stabilisation of FOXP2 gene structure as feature of modern man coincided with the first presence and quick spread of Homo sapiens on the whole Earth. This genetic modification made opportunity for human language, as the basis of abrupt evolution of human intelligence. The brain region being responsible for human language is the left planum temporale, which is much larger in left hemisphere. This shows the most typical human brain asymmetry. In this case the anatomical asymmetry means a clearly defined functional asymmetry as well, where the brain hemispheres act differently. The preference in using hands, the lateralised using of tools resulted in the brain asymmetry, which is the precondition of human language and intelligence. However, it cannot be held anymore, that only humans make tools, because our closest relatives, the chimpanzees are

  15. Microchimerism in the human brain: More questions than answers

    OpenAIRE

    Chan, William F.N.; Nelson, J. Lee

    2013-01-01

    Recently, our group reported the presence of microchimerism (Mc) in the human brain by performing quantitative PCR on female human brain tissues to amplify male DNA. We found brain Mc to be relatively frequent in humans and widely distributed in this organ. Our data also suggested a lower prevalence of brain Mc in women without Alzheimer disease than women without neurological disease. Altogether, these findings suggest that Mc could sometimes influence health and disease of the brain. As fur...

  16. Human freedom and the brain.

    Science.gov (United States)

    Kornhuber, Hans Helmut

    2009-06-01

    Freedom of will does exist, it is self-leadership of man based on reason and ethos. Evidence comes from truth. Determinism cannot be proved since if you try, you mean to prove a truth; but there is no truth without freedom. By contrast for freedom there are many pieces of evidence e.g. science, arts, technology. Freedom utilizes creative abstract thinking with phantasy. Freedom is graded, limited, based on nature, but not developed without good will. We perceive reliably freedom by self-consciousness and in other persons as long as we are sober. Freedom needs intelligence, but is more, it is a creative and moral virtue. The basis for freedom is phylogenesis and culture, in the individual learning and experimenting. Factors in the becoming of freedom are not only genes and environment but also self-discipline. But the creativity of free will is dangerous. Man therefore needs morale. Drives and feelings become humanized, cultural interests are developed. There is a humane nobility from long good will.

  17. Alcohol’s Effects on the Brain: Neuroimaging Results in Humans and Animal Models

    Science.gov (United States)

    Zahr, Natalie M.; Pfefferbaum, Adolf

    2017-01-01

    Brain imaging technology has allowed researchers to conduct rigorous studies of the dynamic course of alcoholism through periods of drinking, sobriety, and relapse and to gain insights into the effects of chronic alcoholism on the human brain. Magnetic resonance imaging (MRI) studies have distinguished alcohol-related brain effects that are permanent from those that are reversible with abstinence. In support of postmortem neuropathological studies showing degeneration of white matter, MRI studies have shown a specific vulnerability of white matter to chronic alcohol exposure. Such studies have demonstrated white-matter volume deficits as well as damage to selective gray-matter structures. Diffusion tensor imaging (DTI), by permitting microstructural characterization of white matter, has extended MRI findings in alcoholics. MR spectroscopy (MRS) allows quantification of several metabolites that shed light on brain biochemical alterations caused by alcoholism. This article focuses on MRI, DTI, and MRS findings in neurological disorders that commonly co-occur with alcoholism, including Wernicke’s encephalopathy, Korsakoff’s syndrome, and hepatic encephalopathy. Also reviewed are neuroimaging findings in animal models of alcoholism and related neurological disorders. This report also suggests that the dynamic course of alcoholism presents a unique opportunity to examine brain structural and functional repair and recovery. PMID:28988573

  18. Puberty and structural brain development in humans.

    Science.gov (United States)

    Herting, Megan M; Sowell, Elizabeth R

    2017-01-01

    Adolescence is a transitional period of physical and behavioral development between childhood and adulthood. Puberty is a distinct period of sexual maturation that occurs during adolescence. Since the advent of magnetic resonance imaging (MRI), human studies have largely examined neurodevelopment in the context of age. A breadth of animal findings suggest that sex hormones continue to influence the brain beyond the prenatal period, with both organizational and activational effects occurring during puberty. Given the animal evidence, human MRI research has also set out to determine how puberty may influence otherwise known patterns of age-related neurodevelopment. Here we review structural-based MRI studies and show that pubertal maturation is a key variable to consider in elucidating sex- and individual- based differences in patterns of human brain development. We also highlight the continuing challenges faced, as well as future considerations, for this vital avenue of research. Copyright © 2016. Published by Elsevier Inc.

  19. Chronological changes in microRNA expression in the developing human brain.

    Directory of Open Access Journals (Sweden)

    Michael P Moreau

    Full Text Available MicroRNAs (miRNAs are endogenously expressed noncoding RNA molecules that are believed to regulate multiple neurobiological processes. Expression studies have revealed distinct temporal expression patterns in the developing rodent and porcine brain, but comprehensive profiling in the developing human brain has not been previously reported.We performed microarray and TaqMan-based expression analysis of all annotated mature miRNAs (miRBase 10.0 as well as 373 novel, predicted miRNAs. Expression levels were measured in 48 post-mortem brain tissue samples, representing gestational ages 14-24 weeks, as well as early postnatal and adult time points.Expression levels of 312 miRNAs changed significantly between at least two of the broad age categories, defined as fetal, young, and adult.We have constructed a miRNA expression atlas of the developing human brain, and we propose a classification scheme to guide future studies of neurobiological function.

  20. Transcriptional profiles of supragranular-enriched genes associate with corticocortical network architecture in the human brain

    Science.gov (United States)

    Krienen, Fenna M.; Yeo, B. T. Thomas; Ge, Tian; Buckner, Randy L.; Sherwood, Chet C.

    2016-01-01

    The human brain is patterned with disproportionately large, distributed cerebral networks that connect multiple association zones in the frontal, temporal, and parietal lobes. The expansion of the cortical surface, along with the emergence of long-range connectivity networks, may be reflected in changes to the underlying molecular architecture. Using the Allen Institute’s human brain transcriptional atlas, we demonstrate that genes particularly enriched in supragranular layers of the human cerebral cortex relative to mouse distinguish major cortical classes. The topography of transcriptional expression reflects large-scale brain network organization consistent with estimates from functional connectivity MRI and anatomical tracing in nonhuman primates. Microarray expression data for genes preferentially expressed in human upper layers (II/III), but enriched only in lower layers (V/VI) of mouse, were cross-correlated to identify molecular profiles across the cerebral cortex of postmortem human brains (n = 6). Unimodal sensory and motor zones have similar molecular profiles, despite being distributed across the cortical mantle. Sensory/motor profiles were anticorrelated with paralimbic and certain distributed association network profiles. Tests of alternative gene sets did not consistently distinguish sensory and motor regions from paralimbic and association regions: (i) genes enriched in supragranular layers in both humans and mice, (ii) genes cortically enriched in humans relative to nonhuman primates, (iii) genes related to connectivity in rodents, (iv) genes associated with human and mouse connectivity, and (v) 1,454 gene sets curated from known gene ontologies. Molecular innovations of upper cortical layers may be an important component in the evolution of long-range corticocortical projections. PMID:26739559

  1. Transcriptional profiles of supragranular-enriched genes associate with corticocortical network architecture in the human brain.

    Science.gov (United States)

    Krienen, Fenna M; Yeo, B T Thomas; Ge, Tian; Buckner, Randy L; Sherwood, Chet C

    2016-01-26

    The human brain is patterned with disproportionately large, distributed cerebral networks that connect multiple association zones in the frontal, temporal, and parietal lobes. The expansion of the cortical surface, along with the emergence of long-range connectivity networks, may be reflected in changes to the underlying molecular architecture. Using the Allen Institute's human brain transcriptional atlas, we demonstrate that genes particularly enriched in supragranular layers of the human cerebral cortex relative to mouse distinguish major cortical classes. The topography of transcriptional expression reflects large-scale brain network organization consistent with estimates from functional connectivity MRI and anatomical tracing in nonhuman primates. Microarray expression data for genes preferentially expressed in human upper layers (II/III), but enriched only in lower layers (V/VI) of mouse, were cross-correlated to identify molecular profiles across the cerebral cortex of postmortem human brains (n = 6). Unimodal sensory and motor zones have similar molecular profiles, despite being distributed across the cortical mantle. Sensory/motor profiles were anticorrelated with paralimbic and certain distributed association network profiles. Tests of alternative gene sets did not consistently distinguish sensory and motor regions from paralimbic and association regions: (i) genes enriched in supragranular layers in both humans and mice, (ii) genes cortically enriched in humans relative to nonhuman primates, (iii) genes related to connectivity in rodents, (iv) genes associated with human and mouse connectivity, and (v) 1,454 gene sets curated from known gene ontologies. Molecular innovations of upper cortical layers may be an important component in the evolution of long-range corticocortical projections.

  2. Viscoelastic parameter identification of human brain tissue.

    Science.gov (United States)

    Budday, S; Sommer, G; Holzapfel, G A; Steinmann, P; Kuhl, E

    2017-10-01

    Understanding the constitutive behavior of the human brain is critical to interpret the physical environment during neurodevelopment, neurosurgery, and neurodegeneration. A wide variety of constitutive models has been proposed to characterize the brain at different temporal and spatial scales. Yet, their model parameters are typically calibrated with a single loading mode and fail to predict the behavior under arbitrary loading conditions. Here we used a finite viscoelastic Ogden model with six material parameters-an elastic stiffness, two viscoelastic stiffnesses, a nonlinearity parameter, and two viscous time constants-to model the characteristic nonlinearity, conditioning, hysteresis and tension-compression asymmetry of the human brain. We calibrated the model under shear, shear relaxation, compression, compression relaxation, and tension for four different regions of the human brain, the cortex, basal ganglia, corona radiata, and corpus callosum. Strikingly, unconditioned gray matter with 0.36kPa and white matter with 0.35kPa were equally stiff, whereas conditioned gray matter with 0.52kPa was three times stiffer than white matter with 0.18kPa. While both unconditioned viscous time constants were larger in gray than in white matter, both conditioned constants were smaller. These rheological differences suggest a different porosity between both tissues and explain-at least in part-the ongoing controversy between reported stiffness differences in gray and white matter. Our unconditioned and conditioned parameter sets are readily available for finite element simulations with commercial software packages that feature Ogden type models at finite deformations. As such, our results have direct implications on improving the accuracy of human brain simulations in health and disease. Copyright © 2017 Elsevier Ltd. All rights reserved.

  3. Alterations in the steroid biosynthetic pathways in the human prefrontal cortex in mood disorders: a postmortem study

    NARCIS (Netherlands)

    Qi, Xin-Rui; Luchetti, S.; Verwer, Ronald W H; Sluiter, Arja A; Mason, Matthew R J; Zhou, Jiang-Ning; Swaab, Dick F

    Altered levels of steroids have been reported in the brain, cerebral spinal fluid and plasma of patients with mood disorders. Neuroimaging studies have reported both functional and structural alterations in mood disorders, for instance in the anterior cingulate cortex (ACC) and dorsolateral

  4. Postmortem detection of hepatitis B, C, and human immunodeficiency virus genomes in blood samples from drug-related deaths in Denmark*

    DEFF Research Database (Denmark)

    Eriksen, Mette Brandt; Jakobsen, Marianne Antonius; Kringsholm, Birgitte

    2009-01-01

    virus (HBV) DNA was detected in 20% (3/15) of anti-HBc-positive/anti-HBs-negative samples, HCV RNA was found in 64% (16/25) of anti-HCV-positive samples, and HIV RNA was detected in 40% (6/15) of anti-HIV-positive samples. The postmortem and antemortem prevalences of HBV DNA and HCV RNA were similar....... Postmortem HIV RNA testing was less sensitive than antemortem testing. Thus, postmortem PCR analysis for HBV and HBC infection is feasible and relevant for demonstrating ongoing infections at death or for transmission analysis during outbreaks....

  5. Neuropathologic correlates of hippocampal atrophy in the elderly: a clinical, pathologic, postmortem MRI study.

    Directory of Open Access Journals (Sweden)

    Robert J Dawe

    Full Text Available The volume of the hippocampus measured with structural magnetic resonance imaging (MRI is increasingly used as a biomarker for Alzheimer's disease (AD. However, the neuropathologic basis of structural MRI changes in the hippocampus in the elderly has not been directly assessed. Postmortem MRI of the aging human brain, combined with histopathology, could be an important tool to address this issue. Therefore, this study combined postmortem MRI and histopathology in 100 elderly subjects from the Rush Memory and Aging Project and the Religious Orders Study. First, to validate the information contained in postmortem MRI data, we tested the hypothesis that postmortem hippocampal volume is smaller in subjects with clinically diagnosed Alzheimer's disease compared to subjects with mild or no cognitive impairment, as observed in antemortem imaging studies. Subsequently, the relations of postmortem hippocampal volume to AD pathology, Lewy bodies, amyloid angiopathy, gross infarcts, microscopic infarcts, and hippocampal sclerosis were examined. It was demonstrated that hippocampal volume was smaller in persons with a clinical diagnosis of AD compared to those with no cognitive impairment (P = 2.6 × 10(-7 or mild cognitive impairment (P = 9.6 × 10(-7. Additionally, hippocampal volume was related to multiple cognitive abilities assessed proximate to death, with its strongest association with episodic memory. Among all pathologies investigated, the most significant factors related to lower hippocampal volume were shown to be AD pathology (P = 0.0018 and hippocampal sclerosis (P = 4.2 × 10(-7. Shape analysis allowed for visualization of the hippocampal regions most associated with volume loss for each of these two pathologies. Overall, this investigation confirmed the relation of hippocampal volume measured postmortem to clinical diagnosis of AD and measures of cognition, and concluded that both AD pathology and hippocampal sclerosis affect hippocampal

  6. Analysis of synthetic cathinones commonly found in bath salts in human performance and postmortem toxicology: method development, drug distribution and interpretation of results.

    Science.gov (United States)

    Marinetti, Laureen J; Antonides, Heather M

    2013-04-01

    To date, the Toxicology Section of the Montgomery County Coroner's Office/Miami Valley Regional Crime Laboratory has identified six synthetic cathinones, commonly found in bath salt products, in 43 cases. Thirty-two cases will be reviewed here, including all of the postmortem cases, all of the human performance cases that had blood specimens submitted, and one urine-only human performance case. The following compounds have been confirmed: 3,4-methylenedioxypyrovalerone (MDPV), 3,4-methylenedioxymethcathinone (methylone), pyrovalerone, pentylone, alpha-pyrrolidinopentiophenone (alpha-PVP) and methedrone. The method also screens for mephedrone, butylone and 3-fluoromethcathinone. Case demographics show 42 white males and females ranging in age from 19 to 53 years. The remaining case was that of a 34-year-old Hispanic male. The 43 cases represent 17 driving under the influence, two domestic violence, four suicides, 12 overdoses, six accidents, one drug-facilitated assault and one homicide. Data will be presented on the distribution of some of these cathinones in various matrices. After review, blood concentration does not appear to predict outcome regarding fatalities or impairment. The highest MDPV concentration occurred in a suicide by hanging and the highest methylone concentration was in a driver. The confirmation method is a liquid-liquid extraction with detection by liquid chromatography triple quadrupole mass spectrometry using electrospray ionization in multiple reaction monitoring mode.

  7. Can immunohistochemistry quantification of Cathepsin-D be useful in the differential diagnosis between vital and post-mortem wounds in humans?

    Science.gov (United States)

    Montisci, Massimo; Corradin, Matteo; Giacomelli, Luciano; Viel, Guido; Cecchetto, Giovanni; Ferrara, Santo Davide

    2014-07-01

    Markers of skin wound vitality and the research methodology used for their determination are still matters of debate in forensic pathology. Cathepsin-D, a lysosomal enzyme, is the most expressed cathepsin in human skin, and although it seems to have the necessary requirements to be utilized as a vitality marker, past research has provided no definitive and clear response on its potential usefulness. Immunohistochemistry with monoclonal antibodies and image analysis has been employed to detect and quantify the expression of Cathepsin-D in human skin wounds. We analyzed skin fragments obtained from 20 living individuals (group A) and 20 persons deceased from natural causes (group B). For each case, five skin fragments were withdrawn at 0', 5', 10', 30', and 90' after abdominal incision. Once the samples were formalin-fixed and paraffin-embedded, we analyzed the expression of Cathepsin-D through the quantification of the immunohistochemistry signal by image analysis. Immunoreactivity was displayed in Pixels of positive area measured by image analysis and converted in micrometer squares. The average levels of Cathepsin-D were higher in group B than in group A, except in three cases which showed a lower expression, with a statistically significant difference of Cathepsin-D expression between the two groups (p vital and post-mortem injuries.

  8. Mechanical characterization of human brain tissue.

    Science.gov (United States)

    Budday, S; Sommer, G; Birkl, C; Langkammer, C; Haybaeck, J; Kohnert, J; Bauer, M; Paulsen, F; Steinmann, P; Kuhl, E; Holzapfel, G A

    2017-01-15

    Mechanics are increasingly recognized to play an important role in modulating brain form and function. Computational simulations are a powerful tool to predict the mechanical behavior of the human brain in health and disease. The success of these simulations depends critically on the underlying constitutive model and on the reliable identification of its material parameters. Thus, there is an urgent need to thoroughly characterize the mechanical behavior of brain tissue and to identify mathematical models that capture the tissue response under arbitrary loading conditions. However, most constitutive models have only been calibrated for a single loading mode. Here, we perform a sequence of multiple loading modes on the same human brain specimen - simple shear in two orthogonal directions, compression, and tension - and characterize the loading-mode specific regional and directional behavior. We complement these three individual tests by combined multiaxial compression/tension-shear tests and discuss effects of conditioning and hysteresis. To explore to which extent the macrostructural response is a result of the underlying microstructural architecture, we supplement our biomechanical tests with diffusion tensor imaging and histology. We show that the heterogeneous microstructure leads to a regional but not directional dependence of the mechanical properties. Our experiments confirm that human brain tissue is nonlinear and viscoelastic, with a pronounced compression-tension asymmetry. Using our measurements, we compare the performance of five common constitutive models, neo-Hookean, Mooney-Rivlin, Demiray, Gent, and Ogden, and show that only the isotropic modified one-term Ogden model is capable of representing the hyperelastic behavior under combined shear, compression, and tension loadings: with a shear modulus of 0.4-1.4kPa and a negative nonlinearity parameter it captures the compression-tension asymmetry and the increase in shear stress under superimposed

  9. The "pseudo-CT myelogram sign": an aid to the diagnosis of underlying brain stem and spinal cord trauma in the presence of major craniocervical region injury on post-mortem CT.

    Science.gov (United States)

    Bolster, F; Ali, Z; Daly, B

    2017-12-01

    To document the detection of underlying low-attenuation spinal cord or brain stem injuries in the presence of the "pseudo-CT myelogram sign" (PCMS) on post-mortem computed tomography (PMCT). The PCMS was identified on PMCT in 20 decedents (11 male, nine female; age 3-83 years, mean age 35.3 years) following fatal blunt trauma at a single forensic centre. Osseous and ligamentous craniocervical region injuries and brain stem or spinal cord trauma detectable on PMCT were recorded. PMCT findings were compared to conventional autopsy in all cases. PMCT-detected transection of the brain stem or high cervical cord in nine of 10 cases compared to autopsy (90% sensitivity). PMCT was 92.86% sensitive in detection of atlanto-occipital joint injuries (n=14), and 100% sensitive for atlanto-axial joint (n=8) injuries. PMCT detected more cervical spine and skull base fractures (n=22, and n=10, respectively) compared to autopsy (n=13, and n=5, respectively). The PCMS is a novel description of a diagnostic finding, which if present in fatal craniocervical region trauma, is very sensitive for underlying spinal cord and brain stem injuries not ordinarily visible on PMCT. Its presence may also predict major osseous and/or ligamentous injuries in this region when anatomical displacement is not evident on PMCT. Copyright © 2017 The Royal College of Radiologists. Published by Elsevier Ltd. All rights reserved.

  10. Imaging retinotopic maps in the human brain

    Science.gov (United States)

    Wandell, Brian A.; Winawer, Jonathan

    2010-01-01

    A quarter-century ago visual neuroscientists had little information about the number and organization of retinotopic maps in human visual cortex. The advent of functional magnetic resonance imaging (MRI), a non-invasive, spatially-resolved technique for measuring brain activity, provided a wealth of data about human retinotopic maps. Just as there are differences amongst nonhuman primate maps, the human maps have their own unique properties. Many human maps can be measured reliably in individual subjects during experimental sessions lasting less than an hour. The efficiency of the measurements and the relatively large amplitude of functional MRI signals in visual cortex make it possible to develop quantitative models of functional responses within specific maps in individual subjects. During this last quarter century, there has also been significant progress in measuring properties of the human brain at a range of length and time scales, including white matter pathways, macroscopic properties of gray and white matter, and cellular and molecular tissue properties. We hope the next twenty-five years will see a great deal of work that aims to integrate these data by modeling the network of visual signals. We don’t know what such theories will look like, but the characterization of human retinotopic maps from the last twenty-five years is likely to be an important part of future ideas about visual computations. PMID:20692278

  11. Hierarchical modularity in human brain functional networks

    CERN Document Server

    Meunier, D; Fornito, A; Ersche, K D; Bullmore, E T; 10.3389/neuro.11.037.2009

    2010-01-01

    The idea that complex systems have a hierarchical modular organization originates in the early 1960s and has recently attracted fresh support from quantitative studies of large scale, real-life networks. Here we investigate the hierarchical modular (or "modules-within-modules") decomposition of human brain functional networks, measured using functional magnetic resonance imaging (fMRI) in 18 healthy volunteers under no-task or resting conditions. We used a customized template to extract networks with more than 1800 regional nodes, and we applied a fast algorithm to identify nested modular structure at several hierarchical levels. We used mutual information, 0 < I < 1, to estimate the similarity of community structure of networks in different subjects, and to identify the individual network that is most representative of the group. Results show that human brain functional networks have a hierarchical modular organization with a fair degree of similarity between subjects, I=0.63. The largest 5 modules at ...

  12. Imaging Monoamine Oxidase in the Human Brain

    Energy Technology Data Exchange (ETDEWEB)

    Fowler, J. S.; Volkow, N. D.; Wang, G-J.; Logan, Jean

    1999-11-10

    Positron emission tomography (PET) studies mapping monoamine oxidase in the human brain have been used to measure the turnover rate for MAO B; to determine the minimum effective dose of a new MAO inhibitor drug lazabemide and to document MAO inhibition by cigarette smoke. These studies illustrate the power of PET and radiotracer chemistry to measure normal biochemical processes and to provide information on the effect of drug exposure on specific molecular targets.

  13. Sense of agency in the human brain

    OpenAIRE

    Haggard, P.

    2017-01-01

    In adult life, people normally know what they are doing. This experience of controlling one's own actions and, through them, the course of events in the outside world is called 'sense of agency'. It forms a central feature of human experience; however, the brain mechanisms that produce the sense of agency have only recently begun to be investigated systematically. This recent progress has been driven by the development of better measures of the experience of agency, improved design of cogniti...

  14. Sex beyond the genitalia: The human brain mosaic

    OpenAIRE

    Joel, Daphna; Berman, Zohar; Tavor, Ido; Wexler, Nadav; Gaber, Olga; Stein, Yaniv; Shefi, Nisan; Pool, Jared; Urchs, Sebastian; Margulies, Daniel S.; Liem, Franziskus; Hänggi, Jürgen; Jäncke, Lutz; Assaf, Yaniv

    2015-01-01

    Whereas a categorical difference in the genitals has always been acknowledged, the question of how far these categories extend into human biology is still not resolved. Documented sex/gender differences in the brain are often taken as support of a sexually dimorphic view of human brains ("female brain" or "male brain"). However, such a distinction would be possible only if sex/gender differences in brain features were highly dimorphic (i.e., little overlap between the forms of these features ...

  15. Towards Developmental Connectomics of the Human Brain

    Directory of Open Access Journals (Sweden)

    Miao eCao

    2016-03-01

    Full Text Available Imaging connectomics based on graph theory has become an effective and unique methodological framework for studying structural and functional connectivity patterns of the developing brain. Normal brain development is characterized by continuous and significant network evolution throughout infancy, childhood and adolescence, following specific maturational patterns. Disruption of these normal changes is associated with neuropsychiatric developmental disorders, such as autism spectrum disorders or attention-deficit hyperactivity disorder. In this review, we focused on the recent progresses regarding typical and atypical development of human brain networks from birth to early adulthood, using a connectomic approach. Specifically, by the time of birth, structural networks already exhibit adult-like organization, with global efficient small-world and modular structures, as well as hub regions and rich-clubs acting as communication backbones. During development, the structure networks are fine-tuned, with increased global integration and robustness and decreased local segregation, as well as the strengthening of the hubs. In parallel, functional networks undergo more dramatic changes during maturation, with both increased integration and segregation during development, as brain hubs shift from primary regions to high order functioning regions, and the organization of modules transitions from a local anatomical emphasis to a more distributed architecture. These findings suggest that structural networks develop earlier than functional networks; meanwhile functional networks demonstrate more dramatic maturational changes with the evolution of structural networks serving as the anatomical backbone. In this review, we also highlighted topologically disorganized characteristics in structural and functional brain networks in several major developmental neuropsychiatric disorders (e.g., autism spectrum disorders, attention-deficit hyperactivity disorder and

  16. Innovative method for carbon dioxide determination in human postmortem cardiac gas samples using headspace-gas chromatography-mass spectrometry and stable labeled isotope as internal standard.

    Science.gov (United States)

    Varlet, V; Smith, F; de Froidmont, S; Dominguez, A; Rinaldi, A; Augsburger, M; Mangin, P; Grabherr, S

    2013-06-19

    A novel approach to measure carbon dioxide (CO2) in gaseous samples, based on a precise and accurate quantification by (13)CO2 internal standard generated in situ is presented. The main goal of this study was to provide an innovative headspace-gas chromatography-mass spectrometry (HS-GC-MS) method applicable in the routine determination of CO2. The main drawback of the GC methods discussed in the literature for CO2 measurement is the lack of a specific internal standard necessary to perform quantification. CO2 measurement is still quantified by external calibration without taking into account analytical problems which can often occur considering gaseous samples. To avoid the manipulation of a stable isotope-labeled gas, we have chosen to generate in situ an internal labeled standard gas ((13)CO2) on the basis of the stoichiometric formation of CO2 by the reaction of hydrochloric acid (HCl) with sodium hydrogen carbonate (NaH(13)CO3). This method allows a precise measurement of CO2 concentration and was validated on various human postmortem gas samples in order to study its efficiency. Copyright © 2013 Elsevier B.V. All rights reserved.

  17. Post-mortem interval estimation of human skeletal remains by micro-computed tomography, mid-infrared microscopic imaging and energy dispersive X-ray mapping

    Science.gov (United States)

    Hatzer-Grubwieser, P.; Bauer, C.; Parson, W.; Unterberger, S. H.; Kuhn, V.; Pemberger, N.; Pallua, Anton K.; Recheis, W.; Lackner, R.; Stalder, R.; Pallua, J. D.

    2015-01-01

    In this study different state-of-the-art visualization methods such as micro-computed tomography (micro-CT), mid-infrared (MIR) microscopic imaging and energy dispersive X-ray (EDS) mapping were evaluated to study human skeletal remains for the determination of the post-mortem interval (PMI). PMI specific features were identified and visualized by overlaying molecular imaging data and morphological tissue structures generated by radiological techniques and microscopic images gained from confocal microscopy (Infinite Focus (IFM)). In this way, a more distinct picture concerning processes during the PMI as well as a more realistic approximation of the PMI were achieved. It could be demonstrated that the gained result in combination with multivariate data analysis can be used to predict the Ca/C ratio and bone volume (BV) over total volume (TV) for PMI estimation. Statistical limitation of this study is the small sample size, and future work will be based on more specimens to develop a screening tool for PMI based on the outcome of this multidimensional approach. PMID:25878731

  18. Assessing various Infrared (IR) microscopic imaging techniques for post-mortem interval evaluation of human skeletal remains

    National Research Council Canada - National Science Library

    Claudia Woess; Seraphin Hubert Unterberger; Clemens Roider; Monika Ritsch-Marte; Nadin Pemberger; Jan Cemper-Kiesslich; Petra Hatzer-Grubwieser; Walther Parson; Johannes Dominikus Pallua

    2017-01-01

    .... In this study the applicability of infrared (IR) microscopic imaging techniques such as reflection-, ATR- and Raman- microscopic imaging for the estimation of the PMI of human skeletal remains was tested...

  19. Brain structures in the sciences and humanities.

    Science.gov (United States)

    Takeuchi, Hikaru; Taki, Yasuyuki; Sekiguchi, Atsushi; Nouchi, Rui; Kotozaki, Yuka; Nakagawa, Seishu; Miyauchi, Carlos Makoto; Iizuka, Kunio; Yokoyama, Ryoichi; Shinada, Takamitsu; Yamamoto, Yuki; Hanawa, Sugiko; Araki, Tsuyoshi; Hashizume, Hiroshi; Sassa, Yuko; Kawashima, Ryuta

    2015-11-01

    The areas of academic interest (sciences or humanities) and area of study have been known to be associated with a number of factors associated with autistic traits. However, despite the vast amount of literature on the psychological and physiological characteristics associated with faculty membership, brain structural characteristics associated with faculty membership have never been investigated directly. In this study, we used voxel-based morphometry to investigate differences in regional gray matter volume (rGMV)/regional white matter volume (rWMV) between science and humanities students to test our hypotheses that brain structures previously robustly shown to be altered in autistic subjects are related to differences in faculty membership. We examined 312 science students (225 males and 87 females) and 179 humanities students (105 males and 74 females). Whole-brain analyses of covariance revealed that after controlling for age, sex, and total intracranial volume, the science students had significantly larger rGMV in an anatomical cluster around the medial prefrontal cortex and the frontopolar area, whereas the humanities students had significantly larger rWMV in an anatomical cluster mainly concentrated around the right hippocampus. These anatomical structures have been linked to autism in previous studies and may mediate cognitive functions that characterize differences in faculty membership. The present results may support the ideas that autistic traits and characteristics of the science students compared with the humanities students share certain characteristics from neuroimaging perspectives. This study improves our understanding of differences in faculty membership which is the link among cognition, biological factors, disorders, and education (academia).

  20. Small-conductance calcium-activated potassium type 2 channels (SK2, KCa2.2) in human brain.

    Science.gov (United States)

    Willis, Michael; Trieb, Maria; Leitner, Irmgard; Wietzorrek, Georg; Marksteiner, Josef; Knaus, Hans-Günther

    2017-03-01

    SK2 (KCa2.2) channels are voltage-independent Ca 2+ -activated K + channels that regulate neuronal excitability in brain regions important for memory formation. In this study, we investigated the distribution and expression of SK2 channels in human brain by Western blot analysis and immunohistochemistry. Immunoblot analysis of human brain indicated expression of four distinct SK2 channel isoforms: the standard, the long and two short isoforms. Immunohistochemistry in paraffin-embedded post-mortem brain sections was performed in the hippocampal formation, amygdala and neocortex. In hippocampus, SK2-like immunoreactivity could be detected in strata oriens and radiatum of area CA1-CA2 and in the molecular layer. In the amygdala, SK2-like immunoreactivity was highest in the basolateral nuclei, while in neocortex, staining was mainly found enriched in layer V. Activation of SK2 channels is thought to regulate neuronal excitability in brain by contributing to the medium afterhyperpolarization. However, SK2 channels are blocked by apamin with a sensitivity that suggests heteromeric channels. The herein first shown expression of SK2 human isoform b in brain could explain the variability of electrophysiological findings observed with SK2 channels.

  1. Post-mortem assessment in vascular dementia: advances and aspirations.

    Science.gov (United States)

    McAleese, Kirsty E; Alafuzoff, Irina; Charidimou, Andreas; De Reuck, Jacques; Grinberg, Lea T; Hainsworth, Atticus H; Hortobagyi, Tibor; Ince, Paul; Jellinger, Kurt; Gao, Jing; Kalaria, Raj N; Kovacs, Gabor G; Kövari, Enikö; Love, Seth; Popovic, Mara; Skrobot, Olivia; Taipa, Ricardo; Thal, Dietmar R; Werring, David; Wharton, Stephen B; Attems, Johannes

    2016-08-26

    Cerebrovascular lesions are a frequent finding in the elderly population. However, the impact of these lesions on cognitive performance, the prevalence of vascular dementia, and the pathophysiology behind characteristic in vivo imaging findings are subject to controversy. Moreover, there are no standardised criteria for the neuropathological assessment of cerebrovascular disease or its related lesions in human post-mortem brains, and conventional histological techniques may indeed be insufficient to fully reflect the consequences of cerebrovascular disease. Here, we review and discuss both the neuropathological and in vivo imaging characteristics of cerebrovascular disease, prevalence rates of vascular dementia, and clinico-pathological correlations. We also discuss the frequent comorbidity of cerebrovascular pathology and Alzheimer's disease pathology, as well as the difficult and controversial issue of clinically differentiating between Alzheimer's disease, vascular dementia and mixed Alzheimer's disease/vascular dementia. Finally, we consider additional novel approaches to complement and enhance current post-mortem assessment of cerebral human tissue. Elucidation of the pathophysiology of cerebrovascular disease, clarification of characteristic findings of in vivo imaging and knowledge about the impact of combined pathologies are needed to improve the diagnostic accuracy of clinical diagnoses.

  2. Segmentation and Visualisation of Human Brain Structures

    Energy Technology Data Exchange (ETDEWEB)

    Hult, Roger

    2003-10-01

    In this thesis the focus is mainly on the development of segmentation techniques for human brain structures and of the visualisation of such structures. The images of the brain are both anatomical images (magnet resonance imaging (MRI) and autoradiography) and functional images that show blood flow (functional magnetic imaging (fMRI), positron emission tomography (PET), and single photon emission tomography (SPECT)). When working with anatomical images, the structures segmented are visible as different parts of the brain, e.g. the brain cortex, the hippocampus, or the amygdala. In functional images, the activity or the blood flow that be seen. Grey-level morphology methods are used in the segmentations to make tissue types in the images more homogenous and minimise difficulties with connections to outside tissue. A method for automatic histogram thresholding is also used. Furthermore, there are binary operations such as logic operation between masks and binary morphology operations. The visualisation of the segmented structures uses either surface rendering or volume rendering. For the visualisation of thin structures, surface rendering is the better choice since otherwise some voxels might be missed. It is possible to display activation from a functional image on the surface of a segmented cortex. A new method for autoradiographic images has been developed, which integrates registration, background compensation, and automatic thresholding to get faster and more reliable results than the standard techniques give.

  3. The genome in three dimensions: a new frontier in human brain research.

    Science.gov (United States)

    Mitchell, Amanda C; Bharadwaj, Rahul; Whittle, Catheryne; Krueger, Winfried; Mirnics, Karoly; Hurd, Yasmin; Rasmussen, Theodore; Akbarian, Schahram

    2014-06-15

    Less than 1.5% of the human genome encodes protein. However, vast portions of the human genome are subject to transcriptional and epigenetic regulation, and many noncoding regulatory DNA elements are thought to regulate the spatial organization of interphase chromosomes. For example, chromosomal "loopings" are pivotal for the orderly process of gene expression, by enabling distal regulatory enhancer or silencer elements to directly interact with proximal promoter and transcription start sites, potentially bypassing hundreds of kilobases of interspersed sequence on the linear genome. To date, however, epigenetic studies in the human brain are mostly limited to the exploration of DNA methylation and posttranslational modifications of the nucleosome core histones. In contrast, very little is known about the regulation of supranucleosomal structures. Here, we show that chromosome conformation capture, a widely used approach to study higher-order chromatin, is applicable to tissue collected postmortem, thereby informing about genome organization in the human brain. We introduce chromosome conformation capture protocols for brain and compare higher-order chromatin structures at the chromosome 6p22.2-22.1 schizophrenia and bipolar disorder susceptibility locus, and additional neurodevelopmental risk genes, (DPP10, MCPH1) in adult prefrontal cortex and various cell culture systems, including neurons derived from reprogrammed skin cells. We predict that the exploration of three-dimensional genome architectures and function will open up new frontiers in human brain research and psychiatric genetics and provide novel insights into the epigenetic risk architectures of regulatory noncoding DNA. Copyright © 2014 Society of Biological Psychiatry. Published by Elsevier Inc. All rights reserved.

  4. Structural brain correlates of human sleep oscillations.

    Science.gov (United States)

    Saletin, Jared M; van der Helm, Els; Walker, Matthew P

    2013-12-01

    Sleep is strongly conserved within species, yet marked and perplexing inter-individual differences in sleep physiology are observed. Combining EEG sleep recordings and high-resolution structural brain imaging, here we demonstrate that the morphology of the human brain offers one explanatory factor of such inter-individual variability. Gray matter volume in interoceptive and exteroceptive cortices correlated with the expression of slower NREM sleep spindle frequencies, supporting their proposed role in sleep protection against conscious perception. Conversely, and consistent with an involvement in declarative memory processing, gray matter volume in bilateral hippocampus was associated with faster NREM sleep spindle frequencies. In contrast to spindles, gray matter volume in the homeostatic sleep-regulating center of the basal forebrain/hypothalamus, together with the medial prefrontal cortex, accounted for individual differences in NREM slow wave oscillations. Together, such findings indicate that the qualitative and quantitative expression of human sleep physiology is significantly related to anatomically specific differences in macroscopic brain structure. Copyright © 2013 Elsevier Inc. All rights reserved.

  5. Deconstructing Anger in the Human Brain.

    Science.gov (United States)

    Gilam, Gadi; Hendler, Talma

    2017-01-01

    Anger may be caused by a wide variety of triggers, and though it has negative consequences on health and well-being, it is also crucial in motivating to take action and approach rather than avoid a confrontation. While anger is considered a survival response inherent in all living creatures, humans are endowed with the mental flexibility that enables them to control and regulate their anger, and adapt it to socially accepted norms. Indeed, a profound interpersonal nature is apparent in most events which evoke anger among humans. Since anger consists of physiological, cognitive, subjective, and behavioral components, it is a contextualized multidimensional construct that poses theoretical and operational difficulties in defining it as a single psychobiological phenomenon. Although most neuroimaging studies have neglected the multidimensionality of anger and thus resulted in brain activations dispersed across the entire brain, there seems to be several reoccurring neural circuits subserving the subjective experience of human anger. Nevertheless, to capture the large variety in the forms and fashions in which anger is experienced, expressed, and regulated, and thus to better portray the related underlying neural substrates, neurobehavioral investigations of human anger should aim to further embed realistic social interactions within their anger induction paradigms.

  6. Inferring human intentions from the brain data

    DEFF Research Database (Denmark)

    Stanek, Konrad

    The human brain is a massively complex organ composed of approximately a hundred billion densely interconnected, interacting neural cells. The neurons are not wired randomly - instead, they are organized in local functional assemblies. It is believed that the complex patterns of dynamic electric...... discharges across the neural tissue are responsible for emergence of high cognitive function, conscious perception and voluntary action. The brain’s capacity to exercise free will, or internally generated free choice, has long been investigated by philosophers, psychologists and neuroscientists. Rather than...... assuming a causal power of conscious will, the neuroscience of volition is based on the premise that "mental states rest on brain processes”, and hence by measuring spatial and temporal correlates of volition in carefully controlled experiments we can infer about their underlying mind processes, including...

  7. Advantages of analyzing postmortem brain samples in routine forensic drug screening—case series of three non-natural deaths tested positive for lysergic acid diethylamide (LSD)

    DEFF Research Database (Denmark)

    Mardal, Marie; Johansen, Sys Stybe; Thomsen, Ragnar

    2017-01-01

    Three case reports are presented, including autopsy findings and toxicological screening results, which were tested positive for the potent hallucinogenic drug lysergic acid diethylamide (LSD). LSD and its main metabolites were quantified in brain tissue and femoral blood, and furthermore hematoma...... levels. The cause of death in case 1 was collision-induced brain injury, while it was drowning in case 2 and 3 and thus not drug intoxication. However, the toxicological findings could help explain the decedent’s inability to cope with brain injury or drowning incidents. The presented findings could help...... establish reference concentrations in brain samples and assist in interpretation of results from forensic drug screening in brain tissue. This is to the author’s knowledge the first report of LSD, iso-LSD, and oxo-HO-LSD measured in brain tissue samples....

  8. Human brain lesion-deficit inference remapped.

    Science.gov (United States)

    Mah, Yee-Haur; Husain, Masud; Rees, Geraint; Nachev, Parashkev

    2014-09-01

    Our knowledge of the anatomical organization of the human brain in health and disease draws heavily on the study of patients with focal brain lesions. Historically the first method of mapping brain function, it is still potentially the most powerful, establishing the necessity of any putative neural substrate for a given function or deficit. Great inferential power, however, carries a crucial vulnerability: without stronger alternatives any consistent error cannot be easily detected. A hitherto unexamined source of such error is the structure of the high-dimensional distribution of patterns of focal damage, especially in ischaemic injury-the commonest aetiology in lesion-deficit studies-where the anatomy is naturally shaped by the architecture of the vascular tree. This distribution is so complex that analysis of lesion data sets of conventional size cannot illuminate its structure, leaving us in the dark about the presence or absence of such error. To examine this crucial question we assembled the largest known set of focal brain lesions (n = 581), derived from unselected patients with acute ischaemic injury (mean age = 62.3 years, standard deviation = 17.8, male:female ratio = 0.547), visualized with diffusion-weighted magnetic resonance imaging, and processed with validated automated lesion segmentation routines. High-dimensional analysis of this data revealed a hidden bias within the multivariate patterns of damage that will consistently distort lesion-deficit maps, displacing inferred critical regions from their true locations, in a manner opaque to replication. Quantifying the size of this mislocalization demonstrates that past lesion-deficit relationships estimated with conventional inferential methodology are likely to be significantly displaced, by a magnitude dependent on the unknown underlying lesion-deficit relationship itself. Past studies therefore cannot be retrospectively corrected, except by new knowledge that would render them redundant

  9. Positive selection on gene expression in the human brain

    DEFF Research Database (Denmark)

    Khaitovich, Philipp; Tang, Kun; Franz, Henriette

    2006-01-01

    Recent work has shown that the expression levels of genes transcribed in the brains of humans and chimpanzees have changed less than those of genes transcribed in other tissues [1] . However, when gene expression changes are mapped onto the evolutionary lineage in which they occurred, the brain...... shows more changes than other tissues in the human lineage compared to the chimpanzee lineage [1] , [2] and [3] . There are two possible explanations for this: either positive selection drove more gene expression changes to fixation in the human brain than in the chimpanzee brain, or genes expressed...... in the brain experienced less purifying selection in humans than in chimpanzees, i.e. gene expression in the human brain is functionally less constrained. The first scenario would be supported if genes that changed their expression in the brain in the human lineage showed more selective sweeps than other genes...

  10. Physical biology of human brain development

    Directory of Open Access Journals (Sweden)

    Silvia eBudday

    2015-07-01

    Full Text Available Neurodevelopment is a complex, dynamic process that involves a precisely orchestrated sequence of genetic, environmental, biochemical, and physical events. Developmental biology and genetics have shaped our understanding of the molecular and cellular mechanisms during neurodevelopment. Recent studies suggest that physical forces play a central role in translating these cellular mechanisms into the complex surface morphology of the human brain. However, the precise impact of neuronal differentiation, migration, and connection on the physical forces during cortical folding remains unknown. Here we review the cellular mechanisms of neurodevelopment with a view towards surface morphogenesis, pattern selection, and evolution of shape. We revisit cortical folding as the instability problem of constrained differential growth in a multi-layered system. To identify the contributing factors of differential growth, we map out the timeline of neurodevelopment in humans and highlight the cellular events associated with extreme radial and tangential expansion. We demonstrate how computational modeling of differential growth can bridge the scales-from phenomena on the cellular level towards form and function on the organ level-to make quantitative, personalized predictions. Physics-based models can quantify cortical stresses, identify critical folding conditions, rationalize pattern selection, and predict gyral wavelengths and gyrification indices. We illustrate that physical forces can explain cortical malformations as emergent properties of developmental disorders. Combining biology and physics holds promise to advance our understanding of human brain development and enable early diagnostics of cortical malformations with the ultimate goal to improve treatment of neurodevelopmental disorders including epilepsy, autism spectrum disorders, and schizophrenia.

  11. Evolvability of Amyloidogenic Proteins in Human Brain

    Science.gov (United States)

    Hashimoto, Makoto; Ho, Gilbert; Sugama, Shuei; Takamatsu, Yoshiki; Shimizu, Yuka; Takenouchi, Takato; Waragai, Masaaki; Masliah, Eliezer

    2018-01-01

     Currently, the physiological roles of amyloidogenic proteins (APs) in human brain, such as amyloid-β and α-synuclein, are elusive. Given that many APs arose by gene duplication and have been resistant against the pressures of natural selection, APs may be associated with some functions that are advantageous for survival of offspring. Nonetheless, evolvability is the sole physiological quality of APs that has been characterized in microorganisms such as yeast. Since yeast and human brain may share similar strategies in coping with diverse range of critical environmental stresses, the objective of this paper was to discuss the potential role of evolvability of APs in aging-associated neurodegenerative disorders, including Alzheimer’s disease and Parkinson’s disease. Given the heterogeneity of APs in terms of structure and cytotoxicity, it is argued that APs might be involved in preconditioning against diverse stresses in human brain. It is further speculated that these stress-related APs, most likely protofibrillar forms, might be transmitted to offspring via the germline, conferring preconditioning against forthcoming stresses. Thus, APs might represent a vehicle for the inheritance of the acquired characteristics against environmental stresses. Curiously, such a characteristic of APs is reminiscent of Charles Darwin’s ‘gemmules’, imagined molecules of heritability described in his pangenesis theory. We propose that evolvability might be a physiological function of APs during the reproductive stage and neurodegenerative diseases could be a by-product effect manifested later in aging. Collectively, our evolvability hypothesis may play a complementary role in the pathophysiology of APs with the conventional amyloid cascade hypothesis. PMID:29439348

  12. Molecular biology of the human brain

    Energy Technology Data Exchange (ETDEWEB)

    Jones, E.G.

    1988-01-01

    This book examines new methods of molecular biology that are providing valuable insights into the human brain, the genes that govern its assembly and function, and the many genetic defects that cause neurological diseases such as Alzheimer's, Cri du Chat syndrome, Huntington's disease, and bipolar depression disorder. In addition, the book reviews techniques in molecular neurobiological research, including the use of affinity reagents, chimeric receptors, and site-directed mutagenesis in localizing the ion channel and cholinergic binding site, and the application of somatic cell genetics in isolating specific chromosomes or chromosomal segments.

  13. Advantages of analyzing postmortem brain samples in routine forensic drug screening-Case series of three non-natural deaths tested positive for lysergic acid diethylamide (LSD).

    Science.gov (United States)

    Mardal, Marie; Johansen, Sys Stybe; Thomsen, Ragnar; Linnet, Kristian

    2017-09-01

    Three case reports are presented, including autopsy findings and toxicological screening results, which were tested positive for the potent hallucinogenic drug lysergic acid diethylamide (LSD). LSD and its main metabolites were quantified in brain tissue and femoral blood, and furthermore hematoma and urine when available. LSD, its main metabolite 2-oxo-3-hydroxy-LSD (oxo-HO-LSD), and iso-LSD were quantified in biological samples according to a previously published procedure involving liquid-liquid extraction and ultra-high performance liquid chromatography-tandem mass spectrometry (UHPLC-MS/MS). LSD was measured in the brain tissue of all presented cases at a concentration level from 0.34-10.8μg/kg. The concentration level in the target organ was higher than in peripheral blood. Additional psychoactive compounds were quantified in blood and brain tissue, though all below toxic concentration levels. The cause of death in case 1 was collision-induced brain injury, while it was drowning in case 2 and 3 and thus not drug intoxication. However, the toxicological findings could help explain the decedent's inability to cope with brain injury or drowning incidents. The presented findings could help establish reference concentrations in brain samples and assist in interpretation of results from forensic drug screening in brain tissue. This is to the author's knowledge the first report of LSD, iso-LSD, and oxo-HO-LSD measured in brain tissue samples. Copyright © 2017 Elsevier B.V. All rights reserved.

  14. Mouse Genetic Models of Human Brain Disorders

    Directory of Open Access Journals (Sweden)

    Celeste eLeung

    2016-03-01

    Full Text Available Over the past three decades, genetic manipulations in mice have been used in neuroscience as a major approach to investigate the in vivo function of genes and their alterations. In particular, gene targeting techniques using embryonic stem cells have revolutionized the field of mammalian genetics and have been at the forefront in the generation of numerous mouse models of human brain disorders. In this review, we will first examine childhood developmental disorders such as autism, intellectual disability, Fragile X syndrome, and Williams-Beuren syndrome. We will then explore psychiatric disorders such as schizophrenia and lastly, neurodegenerative disorders including Alzheimer’s disease and Parkinson’s disease. We will outline the creation of these mouse models that range from single gene deletions, subtle point mutations to multi-gene manipulations, and discuss the key behavioural phenotypes of these mice. Ultimately, the analysis of the models outlined in this review will enhance our understanding of the in vivo role and underlying mechanisms of disease-related genes in both normal brain function and brain disorders, and provide potential therapeutic targets and strategies to prevent and treat these diseases.

  15. Response-to-comments about: "Is it really the method for carbon dioxide determination in human postmortem cardiac gas samples using Headspace-Gas Chromatography-Mass Spectrometry valid?" from T. Saffaj and B. Ihssane.

    Science.gov (United States)

    Varlet, Vincent

    2014-01-31

    Saffaj et al. recently criticized our method of monitoring carbon dioxide in human postmortem cardiac gas samples using Headspace-Gas Chromatography-Mass Spectrometry. According to the authors, their demonstration, based on the latest SFSTP guidelines (established after 2007) fitted for the validation of drug monitoring bioanalytical methods, has put in evidence potential errors. However, our validation approach was built using SFSTP guidelines established before 2007. We justify the use of these guidelines because of the post-mortem context of the study (and not clinical) and the gaseous state of the sample (and not solid or liquid). Using these guidelines, our validation remains correct. Copyright © 2013 Elsevier B.V. All rights reserved.

  16. Asymmetry of Radial and Symmetry of Tangential Neuronal Migration Pathways in Developing Human Fetal Brains.

    Science.gov (United States)

    Miyazaki, Yuta; Song, Jae W; Takahashi, Emi

    2016-01-01

    The radial and tangential neural migration pathways are two major neuronal migration streams in humans that are critical during corticogenesis. Corticogenesis is a complex process of neuronal proliferation that is followed by neuronal migration and the formation of axonal connections. Existing histological assessments of these two neuronal migration pathways have limitations inherent to microscopic studies and are confined to small anatomic regions of interest (ROIs). Thus, little evidence is available about their three-dimensional (3-D) fiber pathways and development throughout the entire brain. In this study, we imaged and analyzed radial and tangential migration pathways in the whole human brain using high-angular resolution diffusion MR imaging (HARDI) tractography. We imaged ten fixed, postmortem fetal (17 gestational weeks (GW), 18 GW, 19 GW, three 20 GW, three 21 GW and 22 GW) and eight in vivo newborn (two 30 GW, 34 GW, 35 GW and four 40 GW) brains with no neurological/pathological conditions. We statistically compared the volume of the left and right radial and tangential migration pathways, and the volume of the radial migration pathways of the anterior and posterior regions of the brain. In specimens 22 GW or younger, the volume of radial migration pathways of the left hemisphere was significantly larger than that of the right hemisphere. The volume of posterior radial migration pathways was also larger when compared to the anterior pathways in specimens 22 GW or younger. In contrast, no significant differences were observed in the radial migration pathways of brains older than 22 GW. Moreover, our study did not identify any significant differences in volumetric laterality in the tangential migration pathways. These results suggest that these two neuronal migration pathways develop and regress differently, and radial neuronal migration varies regionally based on hemispheric and anterior-posterior laterality, potentially explaining regional differences in

  17. A novel approach to quantify different iron forms in ex-vivo human brain tissue

    Science.gov (United States)

    Kumar, Pravin; Bulk, Marjolein; Webb, Andrew; van der Weerd, Louise; Oosterkamp, Tjerk H.; Huber, Martina; Bossoni, Lucia

    2016-12-01

    We propose a novel combination of methods to study the physical properties of ferric ions and iron-oxide nanoparticles in post-mortem human brain, based on the combination of Electron Paramagnetic Resonance (EPR) and SQUID magnetometry. By means of EPR, we derive the concentration of the low molecular weight iron pool, as well as the product of its electron spin relaxation times. Additionally, by SQUID magnetometry we identify iron mineralization products ascribable to a magnetite/maghemite phase and a ferrihydrite (ferritin) phase. We further derive the concentration of magnetite/maghemite and of ferritin nanoparticles. To test out the new combined methodology, we studied brain tissue of an Alzheimer’s patient and a healthy control. Finally, we estimate that the size of the magnetite/maghemite nanoparticles, whose magnetic moments are blocked at room temperature, exceeds 40-50 nm, which is not compatible with the ferritin protein, the core of which is typically 6-8 nm. We believe that this methodology could be beneficial in the study of neurodegenerative diseases such as Alzheimer’s Disease which are characterized by abnormal iron accumulation in the brain.

  18. Normal pediatric postmortem CT appearances

    Energy Technology Data Exchange (ETDEWEB)

    Klein, Willemijn M.; Bosboom, Dennis G.H.; Koopmanschap, Desiree H.J.L.M. [Radboud University Medical Center, Department of Radiology and Nuclear Medicine, Nijmegen (Netherlands); Nievelstein, Rutger A.J. [University Medical Center Utrecht, Department of Radiology, Utrecht (Netherlands); Nikkels, Peter G.J. [University Medical Center Utrecht, Department of Pathology, Utrecht (Netherlands); Rijn, Rick R. van [Academic Medical Center, Department of Radiology, Amsterdam (Netherlands)

    2015-04-01

    Postmortem radiology is a rapidly developing specialty that is increasingly used as an adjunct to or substitute for conventional autopsy. The goal is to find patterns of disease and possibly the cause of death. Postmortem CT images bring to light processes of decomposition most radiologists are unfamiliar with. These postmortem changes, such as the formation of gas and edema, should not be mistaken for pathological processes that occur in living persons. In this review we discuss the normal postmortem thoraco-abdominal changes and how these appear on CT images, as well as how to differentiate these findings from those of pathological processes. (orig.)

  19. Evolution of the human brain: changing brain size and the fossil record.

    Science.gov (United States)

    Park, Min S; Nguyen, Andrew D; Aryan, Henry E; U, Hoi Sang; Levy, Michael L; Semendeferi, Katerina

    2007-03-01

    Although the study of the human brain is a rapidly developing and expanding science, we must take pause to examine the historical and evolutionary events that helped shape the brain of Homo sapiens. From an examination of the human lineage to a discussion of evolutionary principles, we describe the basic principles and theories behind the evolution of the human brain. Specifically, we examine several theories concerning changes in overall brain size during hominid evolution and relate them to the fossil record. This overview is intended to provide a broad understanding of some of the controversial issues that are currently being debated in the multidisciplinary field of brain evolution research.

  20. Comparative primate neuroimaging: insights into human brain evolution.

    Science.gov (United States)

    Rilling, James K

    2014-01-01

    Comparative neuroimaging can identify unique features of the human brain and teach us about human brain evolution. Comparisons with chimpanzees, our closest living primate relative, are critical in this endeavor. Structural magnetic resonance imaging (MRI) has been used to compare brain size development, brain structure proportions and brain aging. Positron emission tomography (PET) imaging has been used to compare resting brain glucose metabolism. Functional MRI (fMRI) has been used to compare auditory and visual system pathways, as well as resting-state networks of connectivity. Finally, diffusion-weighted imaging (DWI) has been used to compare structural connectivity. Collectively, these methods have revealed human brain specializations with respect to development, cortical organization, connectivity, and aging. These findings inform our knowledge of the evolutionary changes responsible for the special features of the modern human mind.

  1. Long-term methamphetamine administration in the vervet monkey models aspects of a human exposure: brain neurotoxicity and behavioral profiles.

    Science.gov (United States)

    Melega, William P; Jorgensen, Matthew J; Laćan, Goran; Way, Baldwin M; Pham, Jamie; Morton, Grenvill; Cho, Arthur K; Fairbanks, Lynn A

    2008-05-01

    Methamphetamine (METH)-associated alterations in the human striatal dopamine (DA) system have been identified with positron emission tomography (PET) imaging and post-mortem studies but have not been well correlated with behavioral changes or cumulative METH intake. Animal studies that model some aspects of human long-term METH abuse can establish dose-dependency profiles of both behavioral changes and potential brain neurotoxicities for identifying consequences of particular cumulative exposures. Based on parameters from human and our monkey pharmacokinetic studies, we modeled a prevalent human METH exposure of daily multiple doses in socially housed vervet monkeys. METH doses were escalated over 33 weeks, with final dosages resulting in estimated peak plasma METH concentrations of 1-3 microM, a range measured in human abusers. With larger METH doses, progressive increases in abnormal behavior and decreases in social behavior were observed on 'injection' days. Anxiety increased on 'no injection' days while aggression decreased throughout the study. Thereafter, during 3 weeks abstinence, differences in baseline vs post-METH behaviors were not observed. Post-mortem analysis of METH brains showed 20% lower striatal DA content while autoradiography studies of precommissural striatum showed 35% lower [3H]WIN35428 binding to the DA transporter. No statistically significant changes were detected for [3H]dihydrotetrabenazine binding to the vesicular monoamine transporter (METH-lower by 10%) or for [3H]SCH 23390 and [3H]raclopride binding to DA D1 and D2 receptors, respectively. Collectively, this long-term, escalating dose METH exposure modeling a human abuse pattern, not associated with high-dose binges, resulted in dose-dependent behavioral effects and caused persistent changes in presynaptic striatal DA system integrity.

  2. The human brain in numbers: a linearly scaled-up primate brain

    Directory of Open Access Journals (Sweden)

    Suzana Herculano-Houzel

    2009-11-01

    Full Text Available The human brain has often been viewed as outstanding among mammalian brains: the most cognitively able, the largest-than-expected from body size, endowed with an overdeveloped cerebral cortex that represents over 80% of brain mass, and purportedly containing 100 billion neurons and 10x more glial cells. Such uniqueness was seemingly necessary to justify the superior cognitive abilities of humans over larger-brained mammals such as elephants and whales. However, our recent studies using a novel method to determine the cellular composition of the brain of humans and other primates as well as of rodents and insectivores show that, since different cellular scaling rules apply to the brains within these orders, brain size can no longer be considered a proxy for the number of neurons in the brain. These studies also showed that the human brain is not exceptional in its cellular composition, as it was found to contain as many neuronal and nonneuronal cells as would be expected of a primate brain of its size. Additionally, the so-called overdeveloped human cerebral cortex holds only 19% of all brain neurons, a fraction that is similar to that found in other mammals. In what regards absolute numbers of neurons, however, the human brain does have two advantages compared to other mammalian brains: compared to rodents, and probably to whales and elephants as well, it is built according to the very economical, space-saving scaling rules that apply to other primates; and, among economically-built primate brains, it is the largest, hence containing the most neurons. These findings argue in favor of a view of cognitive abilities that is centered on absolute numbers of neurons, rather than on body size or encephalization, and call for a re-examination of several concepts related to the exceptionality of the human brain.

  3. The Human Brain in Numbers: A Linearly Scaled-up Primate Brain

    Science.gov (United States)

    Herculano-Houzel, Suzana

    2009-01-01

    The human brain has often been viewed as outstanding among mammalian brains: the most cognitively able, the largest-than-expected from body size, endowed with an overdeveloped cerebral cortex that represents over 80% of brain mass, and purportedly containing 100 billion neurons and 10× more glial cells. Such uniqueness was seemingly necessary to justify the superior cognitive abilities of humans over larger-brained mammals such as elephants and whales. However, our recent studies using a novel method to determine the cellular composition of the brain of humans and other primates as well as of rodents and insectivores show that, since different cellular scaling rules apply to the brains within these orders, brain size can no longer be considered a proxy for the number of neurons in the brain. These studies also showed that the human brain is not exceptional in its cellular composition, as it was found to contain as many neuronal and non-neuronal cells as would be expected of a primate brain of its size. Additionally, the so-called overdeveloped human cerebral cortex holds only 19% of all brain neurons, a fraction that is similar to that found in other mammals. In what regards absolute numbers of neurons, however, the human brain does have two advantages compared to other mammalian brains: compared to rodents, and probably to whales and elephants as well, it is built according to the very economical, space-saving scaling rules that apply to other primates; and, among economically built primate brains, it is the largest, hence containing the most neurons. These findings argue in favor of a view of cognitive abilities that is centered on absolute numbers of neurons, rather than on body size or encephalization, and call for a re-examination of several concepts related to the exceptionality of the human brain. PMID:19915731

  4. Left Brain to Right Brain: Notes from the Human Laboratory.

    Science.gov (United States)

    Baumli, Francis

    1982-01-01

    Examines the implications of the left brain-right brain theory on communications styles in male-female relationships. The author contends that women tend to use the vagueness of their emotional responses manipulatively. Men need to apply rational approaches to increase clarity in communication. (AM)

  5. Advantages of analyzing postmortem brain samples in routine forensic drug screening—case series of three non-natural deaths tested positive for lysergic acid diethylamide (LSD)

    DEFF Research Database (Denmark)

    Mardal, Marie; Johansen, Sys Stybe; Thomsen, Ragnar

    2017-01-01

    Three case reports are presented, including autopsy findings and toxicological screening results, which were tested positive for the potent hallucinogenic drug lysergic acid diethylamide (LSD). LSD and its main metabolites were quantified in brain tissue and femoral blood, and furthermore hematoma...... and urine when available. LSD, its main metabolite 2-oxo-3-hydroxy-LSD (oxo-HO-LSD), and iso-LSD were quantified in biological samples according to a previously published procedure involving liquid-liquid extraction and ultra-high performance liquid chromatography − tandem mass spectrometry (UHPLC......-MS/MS). LSD was measured in the brain tissue of all presented cases at a concentration level from 0.34 −10.8 μg/kg. The concentration level in the target organ was higher than in peripheral blood. Additional psychoactive compounds were quantified in blood and brain tissue, though all below toxic concentration...

  6. Listeriolysin O mediates cytotoxicity against human brain microvascular

    Science.gov (United States)

    Penetration of the brain microvascular endothelial layer is one of the routes L. monocytogenes use to breach the blood-brain barrier. Because host factors in the blood severely limit direct invasion of human brain microvascular endothelial cells (HBMECs) by L. monocytogenes, alternative mechanisms m...

  7. Brain-Computer Interfaces and Human-Computer Interaction

    NARCIS (Netherlands)

    Tan, Desney; Tan, Desney S.; Nijholt, Antinus

    2010-01-01

    Advances in cognitive neuroscience and brain imaging technologies have started to provide us with the ability to interface directly with the human brain. This ability is made possible through the use of sensors that can monitor some of the physical processes that occur within the brain that

  8. Dynamic analysis of the human brain with complex cerebral sulci.

    Science.gov (United States)

    Tseng, Jung-Ge; Huang, Bo-Wun; Ou, Yi-Wen; Yen, Ke-Tien; Wu, Yi-Te

    2016-07-03

    The brain is one of the most vulnerable organs inside the human body. Head accidents often appear in daily life and are easy to cause different level of brain damage inside the skull. Once the brain suffered intense locomotive impact, external injuries, falls, or other accidents, it will result in different degrees of concussion. This study employs finite element analysis to compare the dynamic characteristics between the geometric models of an assumed simple brain tissue and a brain tissue with complex cerebral sulci. It is aimed to understand the free vibration of the internal brain tissue and then to protect the brain from injury caused by external influences. Reverse engineering method is used for a Classic 5-Part Brain (C18) model produced by 3B Scientific Corporation. 3D optical scanner is employed to scan the human brain structure model with complex cerebral sulci and imported into 3D graphics software to construct a solid brain model to simulate the real complex brain tissue. Obtaining the normal mode analysis by inputting the material properties of the true human brain into finite element analysis software, and then to compare the simplified and the complex of brain models.

  9. Postmortem MRI of bladder agenesis

    Energy Technology Data Exchange (ETDEWEB)

    Barber, Brendan R. [St George' s Hospital, Radiology Department, London (United Kingdom); Weber, Martin A. [Great Ormond Street Hospital for Children, Department of Histopathology, London (United Kingdom); Bockenhauer, Detlef [Great Ormond Street Hospital for Children, Department of Nephrology, London (United Kingdom); Hiorns, Melanie P.; McHugh, Kieran [Great Ormond Street Hospital for Children, Radiology Department, London (United Kingdom)

    2011-01-15

    We report a 35-week preterm neonate with bladder agenesis and bilateral dysplastic kidneys. A suprapubic catheter was inadvertently inserted into one of the larger inferior cysts of the left dysplastic kidney. A postmortem MRI scan was performed with the findings being confirmed on autopsy. We are unaware of another postmortem MRI study demonstrating bladder agenesis. (orig.)

  10. Normal pediatric postmortem CT appearances

    NARCIS (Netherlands)

    Klein, Willemijn M.; Bosboom, Dennis G. H.; Koopmanschap, Desiree H. J. L. M.; Nievelstein, Rutger A. J.; Nikkels, Peter G. J.; van Rijn, Rick R.

    Postmortem radiology is a rapidly developing specialty that is increasingly used as an adjunct to or substitute for conventional autopsy. The goal is to find patterns of disease and possibly the cause of death. Postmortem CT images bring to light processes of decomposition most radiologists are

  11. Localized cortical chronic traumatic encephalopathy pathology after single, severe axonal injury in human brain.

    Science.gov (United States)

    Shively, Sharon B; Edgerton, Sarah L; Iacono, Diego; Purohit, Dushyant P; Qu, Bao-Xi; Haroutunian, Vahram; Davis, Kenneth L; Diaz-Arrastia, Ramon; Perl, Daniel P

    2017-03-01

    Chronic traumatic encephalopathy (CTE) is a neurodegenerative disease associated with repetitive mild impact traumatic brain injury from contact sports. Recently, a consensus panel defined the pathognomonic lesion for CTE as accumulations of abnormally hyperphosphorylated tau (p-tau) in neurons (neurofibrillary tangles), astrocytes and cell processes distributed around small blood vessels at sulcal depths in irregular patterns within the cortex. The pathophysiological mechanism for this lesion is unknown. Moreover, a subset of CTE cases harbors cortical β-amyloid plaques. In this study, we analyzed postmortem brain tissues from five institutionalized patients with schizophrenia and history of surgical leucotomy with subsequent survival of at least another 40 years. Because leucotomy involves severing axons bilaterally in prefrontal cortex, this surgical procedure represents a human model of single traumatic brain injury with severe axonal damage and no external impact. We examined cortical tissues at the leucotomy site and at both prefrontal cortex rostral and frontal cortex caudal to the leucotomy site. For comparison, we analyzed brain tissues at equivalent neuroanatomical sites from non-leucotomized patients with schizophrenia, matched in age and gender. All five leucotomy cases revealed severe white matter damage with dense astrogliosis at the axotomy site and also neurofibrillary tangles and p-tau immunoreactive neurites in the overlying gray matter. Four cases displayed p-tau immunoreactivity in neurons, astrocytes and cell processes encompassing blood vessels at cortical sulcal depths in irregular patterns, similar to CTE. The three cases with apolipoprotein E ε4 haplotype showed scattered β-amyloid plaques in the overlying gray matter, but not the two cases with apolipoprotein E ε3/3 genotype. Brain tissue samples from prefrontal cortex rostral and frontal cortex caudal to the leucotomy site, and all cortical samples from the non-leucotomized patients

  12. Aging shapes the population-mean and -dispersion of gene expression in human brains

    Directory of Open Access Journals (Sweden)

    Candice Brinkmeyer-Langford

    2016-08-01

    Full Text Available Human aging is associated with cognitive decline and an increased risk of neurodegenerative disease. Our objective for this study was to evaluate potential relationships between age and variation in gene expression across different regions of the brain. We analyzed the Genotype-Tissue Expression (GTEx data from 54 and 101 tissue samples across 13 brain regions in post-mortem donors of European descent aged between 20 and 70 years at death. After accounting for the effects of covariates and hidden confounding factors, we identified 1,446 protein-coding genes whose expression in one or more brain regions is correlated with chronological age at a false discovery rate of 5%. These genes are involved in various biological processes including apoptosis, mRNA splicing, amino acid biosynthesis, and neurotransmitter transport. The distribution of these genes among brain regions is uneven, suggesting variable regional responses to aging. We also found that the aging response of many genes, e.g., TP37 and C1QA, depends on individuals’ genotypic backgrounds. Finally, using dispersion-specific analysis, we identified genes such as IL7R, MS4A4E, and TERF1/TERF2 whose expressions are differentially dispersed by aging, i.e., variances differ between age groups. Our results demonstrate that age-related gene expression is brain region-specific, genotype-dependent, and associated with both mean and dispersion changes. Our findings provide a foundation for more sophisticated gene expression modeling in the studies of age-related neurodegenerative diseases.

  13. Cristobalite and Hematite Particles in Human Brain.

    Science.gov (United States)

    Kopani, Martin; Kopaniova, A; Trnka, M; Caplovicova, M; Rychly, B; Jakubovsky, J

    2016-11-01

    Foreign substances get into the internal environment of living bodies and accumulate in various organs. Cristobalite and hematite particles in the glial cells of pons cerebri of human brain with diagnosis of Behhet disease with scanning electron microscopy (SEM), energy-dispersive microanalysis (EDX), and transmission electron microscopy (TEM) with diffraction were identified. SEM with EDX revealed the matter of irregular micrometer-sized particles sometimes forming polyhedrons with fibrilar or stratified structure. It was found in some particles Ti, Fe, and Zn. Some particles contained Cu. TEM and electron diffraction showed particles of cristobalite and hematite. The presence of the particles can be a result of environmental effect, disruption of normal metabolism, and transformation of physiologically iron-ferrihydrite into more stable form-hematite. From the size of particles can be drawn the long-term accumulation of elements in glial cells.

  14. Changes in cognitive state alter human functional brain networks

    Directory of Open Access Journals (Sweden)

    Malaak Nasser Moussa

    2011-08-01

    Full Text Available The study of the brain as a whole system can be accomplished using network theory principles. Research has shown that human functional brain networks during a resting state exhibit small-world properties and high degree nodes, or hubs, localized to brain areas consistent with the default mode network (DMN. However, the study of brain networks across different tasks and or cognitive states has been inconclusive. Research in this field is important because the underpinnings of behavioral output are inherently dependent on whether or not brain networks are dynamic. This is the first comprehensive study to evaluate multiple network metrics at a voxel-wise resolution in the human brain at both the whole brain and regional level under various conditions: resting state, visual stimulation, and multisensory (auditory and visual stimulation. Our results show that despite global network stability, functional brain networks exhibit considerable task-induced changes in connectivity, efficiency, and community structure at the regional level.

  15. Cerebral Organoids Recapitulate Epigenomic Signatures of the Human Fetal Brain.

    Science.gov (United States)

    Luo, Chongyuan; Lancaster, Madeline A; Castanon, Rosa; Nery, Joseph R; Knoblich, Juergen A; Ecker, Joseph R

    2016-12-20

    Organoids derived from human pluripotent stem cells recapitulate the early three-dimensional organization of the human brain, but whether they establish the epigenomic and transcriptional programs essential for brain development is unknown. We compared epigenomic and regulatory features in cerebral organoids and human fetal brain, using genome-wide, base resolution DNA methylome and transcriptome sequencing. Transcriptomic dynamics in organoids faithfully modeled gene expression trajectories in early-to-mid human fetal brains. We found that early non-CG methylation accumulation at super-enhancers in both fetal brain and organoids marks forthcoming transcriptional repression in the fully developed brain. Demethylated regions (74% of 35,627) identified during organoid differentiation overlapped with fetal brain regulatory elements. Interestingly, pericentromeric repeats showed widespread demethylation in multiple types of in vitro human neural differentiation models but not in fetal brain. Our study reveals that organoids recapitulate many epigenomic features of mid-fetal human brain and also identified novel non-CG methylation signatures of brain development. Copyright © 2016 The Authors. Published by Elsevier Inc. All rights reserved.

  16. Cerebral Organoids Recapitulate Epigenomic Signatures of the Human Fetal Brain

    Directory of Open Access Journals (Sweden)

    Chongyuan Luo

    2016-12-01

    Full Text Available Organoids derived from human pluripotent stem cells recapitulate the early three-dimensional organization of the human brain, but whether they establish the epigenomic and transcriptional programs essential for brain development is unknown. We compared epigenomic and regulatory features in cerebral organoids and human fetal brain, using genome-wide, base resolution DNA methylome and transcriptome sequencing. Transcriptomic dynamics in organoids faithfully modeled gene expression trajectories in early-to-mid human fetal brains. We found that early non-CG methylation accumulation at super-enhancers in both fetal brain and organoids marks forthcoming transcriptional repression in the fully developed brain. Demethylated regions (74% of 35,627 identified during organoid differentiation overlapped with fetal brain regulatory elements. Interestingly, pericentromeric repeats showed widespread demethylation in multiple types of in vitro human neural differentiation models but not in fetal brain. Our study reveals that organoids recapitulate many epigenomic features of mid-fetal human brain and also identified novel non-CG methylation signatures of brain development.

  17. "Messing with the Mind: Evolutionary Challenges to Human Brain Augmentation

    Directory of Open Access Journals (Sweden)

    ARTHUR eSANIOTIS

    2014-09-01

    Full Text Available The issue of brain augmentation has received considerable scientific attention over the last two decades. A key factor to brain augmentation that has been widely overlooked are the complex evolutionary processes which have taken place in evolving the human brain to its current state of functioning. Like other bodily organs, the human brain has been subject to the forces of biological adaptation. The structure and function of the brain, is very complex and only now we are beginning to understand some of the basic concepts of cognition. Therefore, this article proposes that brain-machine interfacing and nootropics are not going to produce augmented brains because we do not understand enough about how evolutionary pressures have informed the neural networks which support human cognitive faculties.

  18. Pharmacoepigenetics of the role of DNA methylation in μ-opioid receptor expression in different human brain regions.

    Science.gov (United States)

    Knothe, Claudia; Oertel, Bruno G; Ultsch, Alfred; Kettner, Mattias; Schmidt, Peter Harald; Wunder, Cora; Toennes, Stefan W; Geisslinger, Gerd; Lötsch, Jörn

    2016-12-01

    Exposure to opioids has been associated with epigenetic effects. Studies in rodents suggested a role of varying degrees of DNA methylation in the differential regulation of μ-opioid receptor expression across the brain. In a translational investigation, using tissue acquired postmortem from 21 brain regions of former opiate addicts, representing a human cohort with chronic opioid exposure, μ-opioid receptor expression was analyzed at the level of DNA methylation, mRNA and protein. While high or low μ-opioid receptor expression significantly correlated with local OPRM1 mRNA levels, there was no corresponding association with OPRM1 methylation status. Additional experiments in human cell lines showed that changes in DNA methylation associated with changes in μ-opioid expression were an order of magnitude greater than differences in brain. Hence, different degrees of DNA methylation associated with chronic opioid exposure are unlikely to exert a major role in the region-specificity of μ-opioid receptor expression in the human brain.

  19. Lower Leg Injury Reference Values and Risk Curves from Survival Analysis for Male and Female Dummies: Meta-analysis of Postmortem Human Subject Tests.

    Science.gov (United States)

    Yoganandan, Narayan; Arun, Mike W J; Pintar, Frank A; Banerjee, Anjishnu

    2015-01-01

    Derive lower leg injury risk functions using survival analysis and determine injury reference values (IRV) applicable to human mid-size male and small-size female anthropometries by conducting a meta-analysis of experimental data from different studies under axial impact loading to the foot-ankle-leg complex. Specimen-specific dynamic peak force, age, total body mass, and injury data were obtained from tests conducted by applying the external load to the dorsal surface of the foot of postmortem human subject (PMHS) foot-ankle-leg preparations. Calcaneus and/or tibia injuries, alone or in combination and with/without involvement of adjacent articular complexes, were included in the injury group. Injury and noninjury tests were included. Maximum axial loads recorded by a load cell attached to the proximal end of the preparation were used. Data were analyzed by treating force as the primary variable. Age was considered as the covariate. Data were censored based on the number of tests conducted on each specimen and whether it remained intact or sustained injury; that is, right, left, and interval censoring. The best fits from different distributions were based on the Akaike information criterion; mean and plus and minus 95% confidence intervals were obtained; and normalized confidence interval sizes (quality indices) were determined at 5, 10, 25, and 50% risk levels. The normalization was based on the mean curve. Using human-equivalent age as 45 years, data were normalized and risk curves were developed for the 50th and 5th percentile human size of the dummies. Out of the available 114 tests (76 fracture and 38 no injury) from 5 groups of experiments, survival analysis was carried out using 3 groups consisting of 62 tests (35 fracture and 27 no injury). Peak forces associated with 4 specific risk levels at 25, 45, and 65 years of age are given along with probability curves (mean and plus and minus 95% confidence intervals) for PMHS and normalized data applicable to

  20. From reverse transcription to human brain tumors

    Directory of Open Access Journals (Sweden)

    Dmitrenko V. V.

    2013-05-01

    Full Text Available Reverse transcriptase from avian myeloblastosis virus (AMV was the subject of the study, from which the investi- gations of the Department of biosynthesis of nucleic acids were started. Production of AMV in grams quantities and isolation of AMV reverse transcriptase were established in the laboratory during the seventies of the past cen- tury and this initiated research on the cDNA synthesis, cloning and investigation of the structure and functions of the eukaryotic genes. Structures of salmon insulin and insulin-like growth factor (IGF family genes and their transcripts were determined during long-term investigations. Results of two modern techniques, microarray-ba- sed hybridization and SAGE, were used for the identification of the genes differentially expressed in astrocytic gliomas and human normal brain. Comparison of SAGE results on the genes overexpressed in glioblastoma with the results of microarray analysis revealed a limited number of common genes. 105 differentially expressed genes, common to both methods, can be included in the list of candidates for the molecular typing of glioblastoma. The first experiments on the classification of glioblastomas based on the data of the 20 genes expression were conducted by using of artificial neural network analysis. The results of these experiments showed that the expression profiles of these genes in 224 glioblastoma samples and 74 normal brain samples could be according to the Koho- nen’s maps. The CHI3L1 and CHI3L2 genes of chitinase-like cartilage protein were revealed among the most overexpressed genes in glioblastoma, which could have prognostic and diagnostic potential. Results of in vitro experiments demonstrated that both proteins, CHI3L1 and CHI3L2, may initiate the phosphorylation of ERK1/ ERK2 and AKT kinases leading to the activation of MAPK/ERK1/2 and PI3K/AKT signaling cascades in human embryonic kidney 293 cells, human glioblastoma U87MG, and U373 cells. The new human cell line

  1. Energetic and nutritional constraints on infant brain development: implications for brain expansion during human evolution.

    Science.gov (United States)

    Cunnane, Stephen C; Crawford, Michael A

    2014-12-01

    The human brain confronts two major challenges during its development: (i) meeting a very high energy requirement, and (ii) reliably accessing an adequate dietary source of specific brain selective nutrients needed for its structure and function. Implicitly, these energetic and nutritional constraints to normal brain development today would also have been constraints on human brain evolution. The energetic constraint was solved in large measure by the evolution in hominins of a unique and significant layer of body fat on the fetus starting during the third trimester of gestation. By providing fatty acids for ketone production that are needed as brain fuel, this fat layer supports the brain's high energy needs well into childhood. This fat layer also contains an important reserve of the brain selective omega-3 fatty acid, docosahexaenoic acid (DHA), not available in other primates. Foremost amongst the brain selective minerals are iodine and iron, with zinc, copper and selenium also being important. A shore-based diet, i.e., fish, molluscs, crustaceans, frogs, bird's eggs and aquatic plants, provides the richest known dietary sources of brain selective nutrients. Regular access to these foods by the early hominin lineage that evolved into humans would therefore have helped free the nutritional constraint on primate brain development and function. Inadequate dietary supply of brain selective nutrients still has a deleterious impact on human brain development on a global scale today, demonstrating the brain's ongoing vulnerability. The core of the shore-based paradigm of human brain evolution proposes that sustained access by certain groups of early Homo to freshwater and marine food resources would have helped surmount both the nutritional as well as the energetic constraints on mammalian brain development. Copyright © 2014 Elsevier Ltd. All rights reserved.

  2. Postmortem Biochemistry and Toxicology

    Directory of Open Access Journals (Sweden)

    Robert Flanagan

    2017-04-01

    Full Text Available The aim of postmortem biochemistry and toxicology is either to help establish the cause of death, or to gain information on events immediately before death. If self-poisoning is suspected, the diagnosis may be straightforward and all that could be required is confirmation of the agents involved. However, if the cause of death is not immediately obvious then suspicion of possible poisoning or of conditions such as alcoholic ketoacidosis is of course crucial. On the other hand, it may be important to investigate adherence to prescribed therapy, for example with anticonvulsants or antipsychotics, hence sensitive methods are required. Blood sampling (needle aspiration, peripheral vein, for example femoral, ideally after proximal ligation before opening the body minimizes the risk of sample contamination with, for example, gut contents or urine. Other specimens (stomach contents, urine, liver, vitreous humor may also be valuable and may be needed to corroborate unexpected or unusual findings in the absence of other evidence. The site of sampling should always be recorded. The availability of antemortem specimens should not necessarily preclude postmortem sampling. Appropriate sample preservation, transport, and storage are mandatory. Interpretation of analytical toxicology results must take into account what is known of the pharmacokinetics and toxicology of the agent(s in question, the circumstances under which death occurred including the mechanism of exposure, and other factors such as the stability of the analyte(s and the analytical methods used. It is important to realise that changes may occur in the composition of body fluids, even peripheral blood, after death. Such changes are likely to be greater after attempted resuscitation, and with centrally-acting drugs with large volumes of distribution given chronically, and may perhaps be minimised by prompt refrigeration of the body and performing the autopsy quickly.

  3. Lipidomics of human brain aging and Alzheimer's disease pathology.

    Science.gov (United States)

    Naudí, Alba; Cabré, Rosanna; Jové, Mariona; Ayala, Victoria; Gonzalo, Hugo; Portero-Otín, Manuel; Ferrer, Isidre; Pamplona, Reinald

    2015-01-01

    Lipids stimulated and favored the evolution of the brain. Adult human brain contains a large amount of lipids, and the largest diversity of lipid classes and lipid molecular species. Lipidomics is defined as "the full characterization of lipid molecular species and of their biological roles with respect to expression of proteins involved in lipid metabolism and function, including gene regulation." Therefore, the study of brain lipidomics can help to unravel the diversity and to disclose the specificity of these lipid traits and its alterations in neural (neurons and glial) cells, groups of neural cells, brain, and fluids such as cerebrospinal fluid and plasma, thus helping to uncover potential biomarkers of human brain aging and Alzheimer disease. This review will discuss the lipid composition of the adult human brain. We first consider a brief approach to lipid definition, classification, and tools for analysis from the new point of view that has emerged with lipidomics, and then turn to the lipid profiles in human brain and how lipids affect brain function. Finally, we focus on the current status of lipidomics findings in human brain aging and Alzheimer's disease pathology. Neurolipidomics will increase knowledge about physiological and pathological functions of brain cells and will place the concept of selective neuronal vulnerability in a lipid context. © 2015 Elsevier Inc. All rights reserved.

  4. Evolutionary origins of human brain and spirituality.

    Science.gov (United States)

    Henneberg, Maciej; Saniotis, Arthur

    2009-12-01

    Evolving brains produce minds. Minds operate on imaginary entities. Thus they can create what does not exist in the physical world. Spirits can be deified. Perception of spiritual entities is emotional--organic. Spirituality is a part of culture while culture is an adaptive mechanism of human groups as it allows for technology and social organization to support survival and reproduction. Humans are not rational, they are emotional. Most of explanations of the world, offered by various cultures, involve an element of "fiat", a will of a higher spiritual being, or a reference to some ideal. From this the rules of behaviour are deduced. These rules are necessary to maintain social peace and allow a complex unit consisting of individuals of both sexes and all ages to function in a way ensuring their reproductive success and thus survival. There is thus a direct biological benefit of complex ideological superstructure of culture. This complex superstructure most often takes a form of religion in which logic is mixed with appeals to emotions based on images of spiritual beings. God is a consequence of natural evolution. Whether a deity is a cause of this evolution is difficult to discover, but existence of a deity cannot be questioned.

  5. Macroscopic networks in the human brain: mapping connectivity in healthy and damaged brains

    NARCIS (Netherlands)

    Nijhuis, E.H.J.

    2013-01-01

    The human brain contains a network of interconnected neurons. Recent advances in functional and structural in-vivo magnetic resonance neuroimaging (MRI) techniques have provided opportunities to model the networks of the human brain on a macroscopic scale. This dissertation investigates the

  6. [125I]RTI-55 binding to cocaine-sensitive dopaminergic and serotonergic uptake sites in the human brain.

    Science.gov (United States)

    Little, K Y; Kirkman, J A; Carroll, F I; Breese, G R; Duncan, G E

    1993-12-01

    [125I]RTI-55 is a newly synthesized cocaine congener that may offer advantages over other ligands previously used to examine cocaine binding sites. However, the in vitro pharmacological and anatomical characterization of [125I]RTI-55 binding sites has not been previously performed in human brain. To determine the specificity, stability, and feasibility of [125I]RTI-55 for use in radioligand binding assays in postmortem human tissue, a series of experiments were performed characterizing [125I]RTI-55 binding sites in human brain using homogenized membrane preparations and quantitative autoradiography. Analysis of the association, dissociation, and saturation data favored two-phase processes. A curve-fitting analysis of the data derived in saturation experiments found a high-affinity site with KD = 66 +/- 35 pM and Bmax = 13.2 +/- 10.1 pmol/g of tissue and a low-affinity site with KD = 1.52 +/- 0.55 nM and Bmax of 47.5 +/- 11.2 pmol/g of tissue. Competition by ligands known to bind to the dopamine transporter showed a rank order of RTI-55 > GBR-12909 > maxindol > WIN 35428 > = methylphenidate > (-)-cocaine > buproprion > (+)-amphetamine. Binding to serotonergic sites was evaluated in the midbrain. Results of the saturation experiment performed autoradiographically in the midbrain showed a single site with KD = 370 +/- 84 pM. It appears that [125I]RTI-55 should be useful in further studies of the regulation of cocaine binding sites using postmortem human specimens.

  7. Common Postmortem Computed Tomography Findings Following Atraumatic Death: Differentiation between Normal Postmortem Changes and Pathologic Lesions

    OpenAIRE

    Ishida, Masanori; Gonoi, Wataru; Okuma, Hidemi; Shirota, Go; Shintani, Yukako; Abe, Hiroyuki; Takazawa, Yutaka; Fukayama, Masashi; Ohtomo, Kuni

    2015-01-01

    Computed tomography (CT) is widely used in postmortem investigations as an adjunct to the traditional autopsy in forensic medicine. To date, several studies have described postmortem CT findings as being caused by normal postmortem changes. However, on interpretation, postmortem CT findings that are seemingly due to normal postmortem changes initially, may not have been mere postmortem artifacts. In this pictorial essay, we describe the common postmortem CT findings in cases of atraumatic in-...

  8. A validated method for simultaneous determination of codeine, codeine-6-glucuronide, norcodeine, morphine, morphine-3-glucuronide and morphine-6-glucuronide in post-mortem blood, vitreous fluid, muscle, fat and brain tissue by LC-MS.

    Science.gov (United States)

    Frost, Joachim; Løkken, Trine N; Brede, Wenche R; Hegstad, Solfrid; Nordrum, Ivar S; Slørdal, Lars

    2015-04-01

    The toxicodynamics and, to a lesser degree, toxicokinetics of the widely used opiate codeine remain a matter of controversy. To address this issue, analytical methods capable of providing reliable quantification of codeine metabolites alongside codeine concentrations are required. This article presents a validated method for simultaneous determination of codeine, codeine metabolites codeine-6-glucuronide (C6G), norcodeine and morphine, and morphine metabolites morphine-3-glucuronide (M3G) and morphine-6-glucuronide (M6G) in post-mortem whole blood, vitreous fluid, muscle, fat and brain tissue by high-performance liquid chromatography mass spectrometry. Samples were prepared by solid-phase extraction. The validated ranges were 1.5-300 ng/mL for codeine, norcodeine and morphine, and 23-4,600 ng/mL for C6G, M3G and M6G, with exceptions for norcodeine in muscle (3-300 ng/mL), morphine in muscle, fat and brain (3-300 ng/mL) and M6G in fat (46-4,600 ng/mL). Within-run and between-run accuracy (88.1-114.1%) and precision (CV 0.6-12.7%), matrix effects (CV 0.3-13.5%) and recovery (57.8-94.1%) were validated at two concentration levels; 3 and 150 ng/mL for codeine, norcodeine and morphine, and 46 and 2,300 ng/mL for C6G, M3G and M6G. Freeze-thaw and long-term stability (6 months at -80°C) was assessed, showing no significant changes in analyte concentrations (-12 to +8%). The method was applied in two authentic forensic autopsy cases implicating codeine in both therapeutic and presumably lethal concentration levels. © The Author 2015. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

  9. A Culture-Behavior-Brain Loop Model of Human Development.

    Science.gov (United States)

    Han, Shihui; Ma, Yina

    2015-11-01

    Increasing evidence suggests that cultural influences on brain activity are associated with multiple cognitive and affective processes. These findings prompt an integrative framework to account for dynamic interactions between culture, behavior, and the brain. We put forward a culture-behavior-brain (CBB) loop model of human development that proposes that culture shapes the brain by contextualizing behavior, and the brain fits and modifies culture via behavioral influences. Genes provide a fundamental basis for, and interact with, the CBB loop at both individual and population levels. The CBB loop model advances our understanding of the dynamic relationships between culture, behavior, and the brain, which are crucial for human phylogeny and ontogeny. Future brain changes due to cultural influences are discussed based on the CBB loop model. Copyright © 2015 Elsevier Ltd. All rights reserved.

  10. Metabolic costs and evolutionary implications of human brain development.

    Science.gov (United States)

    Kuzawa, Christopher W; Chugani, Harry T; Grossman, Lawrence I; Lipovich, Leonard; Muzik, Otto; Hof, Patrick R; Wildman, Derek E; Sherwood, Chet C; Leonard, William R; Lange, Nicholas

    2014-09-09

    The high energetic costs of human brain development have been hypothesized to explain distinctive human traits, including exceptionally slow and protracted preadult growth. Although widely assumed to constrain life-history evolution, the metabolic requirements of the growing human brain are unknown. We combined previously collected PET and MRI data to calculate the human brain's glucose use from birth to adulthood, which we compare with body growth rate. We evaluate the strength of brain-body metabolic trade-offs using the ratios of brain glucose uptake to the body's resting metabolic rate (RMR) and daily energy requirements (DER) expressed in glucose-gram equivalents (glucosermr% and glucoseder%). We find that glucosermr% and glucoseder% do not peak at birth (52.5% and 59.8% of RMR, or 35.4% and 38.7% of DER, for males and females, respectively), when relative brain size is largest, but rather in childhood (66.3% and 65.0% of RMR and 43.3% and 43.8% of DER). Body-weight growth (dw/dt) and both glucosermr% and glucoseder% are strongly, inversely related: soon after birth, increases in brain glucose demand are accompanied by proportionate decreases in dw/dt. Ages of peak brain glucose demand and lowest dw/dt co-occur and subsequent developmental declines in brain metabolism are matched by proportionate increases in dw/dt until puberty. The finding that human brain glucose demands peak during childhood, and evidence that brain metabolism and body growth rate covary inversely across development, support the hypothesis that the high costs of human brain development require compensatory slowing of body growth rate.

  11. Human brain networks function in connectome-specific harmonic waves.

    Science.gov (United States)

    Atasoy, Selen; Donnelly, Isaac; Pearson, Joel

    2016-01-21

    A key characteristic of human brain activity is coherent, spatially distributed oscillations forming behaviour-dependent brain networks. However, a fundamental principle underlying these networks remains unknown. Here we report that functional networks of the human brain are predicted by harmonic patterns, ubiquitous throughout nature, steered by the anatomy of the human cerebral cortex, the human connectome. We introduce a new technique extending the Fourier basis to the human connectome. In this new frequency-specific representation of cortical activity, that we call 'connectome harmonics', oscillatory networks of the human brain at rest match harmonic wave patterns of certain frequencies. We demonstrate a neural mechanism behind the self-organization of connectome harmonics with a continuous neural field model of excitatory-inhibitory interactions on the connectome. Remarkably, the critical relation between the neural field patterns and the delicate excitation-inhibition balance fits the neurophysiological changes observed during the loss and recovery of consciousness.

  12. The immune response of the human brain to abdominal surgery

    DEFF Research Database (Denmark)

    Forsberg, Anton; Cervenka, Simon; Jonsson Fagerlund, Malin

    2017-01-01

    OBJECTIVE: Surgery launches a systemic inflammatory reaction that reaches the brain and associates with immune activation and cognitive decline. Although preclinical studies have in part described this systemic-to-brain signaling pathway, we lack information on how these changes appear in humans....... This study examines the short- and long-term impact of abdominal surgery on the human brain immune system by positron emission tomography (PET) in relation to blood immune reactivity, plasma inflammatory biomarkers, and cognitive function. METHODS: Eight males undergoing prostatectomy under general...... to change in [(11) C]PBR28 binding (p = 0.027). INTERPRETATION: This study translates preclinical data on changes in the brain immune system after surgery to humans, and suggests an interplay between the human brain and the inflammatory response of the peripheral innate immune system. These findings may...

  13. Mapping human whole-brain structural networks with diffusion MRI.

    Directory of Open Access Journals (Sweden)

    Patric Hagmann

    Full Text Available Understanding the large-scale structural network formed by neurons is a major challenge in system neuroscience. A detailed connectivity map covering the entire brain would therefore be of great value. Based on diffusion MRI, we propose an efficient methodology to generate large, comprehensive and individual white matter connectional datasets of the living or dead, human or animal brain. This non-invasive tool enables us to study the basic and potentially complex network properties of the entire brain. For two human subjects we find that their individual brain networks have an exponential node degree distribution and that their global organization is in the form of a small world.

  14. From Brain-Environment Connections to Temporal Dynamics and Social Interaction: Principles of Human Brain Function.

    Science.gov (United States)

    Hari, Riitta

    2017-06-07

    Experimental data about brain function accumulate faster than does our understanding of how the brain works. To tackle some general principles at the grain level of behavior, I start from the omnipresent brain-environment connection that forces regularities of the physical world to shape the brain. Based on top-down processing, added by sparse sensory information, people are able to form individual "caricature worlds," which are similar enough to be shared among other people and which allow quick and purposeful reactions to abrupt changes. Temporal dynamics and social interaction in natural environments serve as further essential organizing principles of human brain function. Copyright © 2017 Elsevier Inc. All rights reserved.

  15. [Post-mortem microbiology analysis].

    Science.gov (United States)

    Fernández-Rodríguez, Amparo; Alberola, Juan; Cohen, Marta Cecilia

    2013-12-01

    Post-mortem microbiology is useful in both clinical and forensic autopsies, and allows a suspected infection to be confirmed. Indeed, it is routinely applied to donor studies in the clinical setting, as well as in sudden and unexpected death in the forensic field. Implementation of specific sampling techniques in autopsy can minimize the possibility of contamination, making interpretation of the results easier. Specific interpretation criteria for post-mortem cultures, the use of molecular diagnosis, and its fusion with molecular biology and histopathology have led to post-mortem microbiology playing a major role in autopsy. Multidisciplinary work involving microbiologists, pathologists, and forensic physicians will help to improve the achievements of post-mortem microbiology, prevent infectious diseases, and contribute to a healthier population. Crown Copyright © 2012. Published by Elsevier Espana. All rights reserved.

  16. Sex beyond the genitalia: The human brain mosaic.

    Science.gov (United States)

    Joel, Daphna; Berman, Zohar; Tavor, Ido; Wexler, Nadav; Gaber, Olga; Stein, Yaniv; Shefi, Nisan; Pool, Jared; Urchs, Sebastian; Margulies, Daniel S; Liem, Franziskus; Hänggi, Jürgen; Jäncke, Lutz; Assaf, Yaniv

    2015-12-15

    Whereas a categorical difference in the genitals has always been acknowledged, the question of how far these categories extend into human biology is still not resolved. Documented sex/gender differences in the brain are often taken as support of a sexually dimorphic view of human brains ("female brain" or "male brain"). However, such a distinction would be possible only if sex/gender differences in brain features were highly dimorphic (i.e., little overlap between the forms of these features in males and females) and internally consistent (i.e., a brain has only "male" or only "female" features). Here, analysis of MRIs of more than 1,400 human brains from four datasets reveals extensive overlap between the distributions of females and males for all gray matter, white matter, and connections assessed. Moreover, analyses of internal consistency reveal that brains with features that are consistently at one end of the "maleness-femaleness" continuum are rare. Rather, most brains are comprised of unique "mosaics" of features, some more common in females compared with males, some more common in males compared with females, and some common in both females and males. Our findings are robust across sample, age, type of MRI, and method of analysis. These findings are corroborated by a similar analysis of personality traits, attitudes, interests, and behaviors of more than 5,500 individuals, which reveals that internal consistency is extremely rare. Our study demonstrates that, although there are sex/gender differences in the brain, human brains do not belong to one of two distinct categories: male brain/female brain.

  17. Brain-Computer Interface Controlled Cyborg: Establishing a Functional Information Transfer Pathway from Human Brain to Cockroach Brain.

    Science.gov (United States)

    Li, Guangye; Zhang, Dingguo

    2016-01-01

    An all-chain-wireless brain-to-brain system (BTBS), which enabled motion control of a cyborg cockroach via human brain, was developed in this work. Steady-state visual evoked potential (SSVEP) based brain-computer interface (BCI) was used in this system for recognizing human motion intention and an optimization algorithm was proposed in SSVEP to improve online performance of the BCI. The cyborg cockroach was developed by surgically integrating a portable microstimulator that could generate invasive electrical nerve stimulation. Through Bluetooth communication, specific electrical pulse trains could be triggered from the microstimulator by BCI commands and were sent through the antenna nerve to stimulate the brain of cockroach. Serial experiments were designed and conducted to test overall performance of the BTBS with six human subjects and three cockroaches. The experimental results showed that the online classification accuracy of three-mode BCI increased from 72.86% to 78.56% by 5.70% using the optimization algorithm and the mean response accuracy of the cyborgs using this system reached 89.5%. Moreover, the results also showed that the cyborg could be navigated by the human brain to complete walking along an S-shape track with the success rate of about 20%, suggesting the proposed BTBS established a feasible functional information transfer pathway from the human brain to the cockroach brain.

  18. Toward discovery science of human brain function

    DEFF Research Database (Denmark)

    Biswal, Bharat B; Mennes, Maarten; Zuo, Xi-Nian

    2010-01-01

    Although it is being successfully implemented for exploration of the genome, discovery science has eluded the functional neuroimaging community. The core challenge remains the development of common paradigms for interrogating the myriad functional systems in the brain without the constraints...... individual's functional connectome exhibits unique features, with stable, meaningful interindividual differences in connectivity patterns and strengths. Comprehensive mapping of the functional connectome, and its subsequent exploitation to discern genetic influences and brain-behavior relationships...... in the brain. To initiate discovery science of brain function, the 1000 Functional Connectomes Project dataset is freely accessible at www.nitrc.org/projects/fcon_1000/....

  19. Brain banking: opportunities, challenges and meaning for the future.

    Science.gov (United States)

    Kretzschmar, Hans

    2009-01-01

    Brain banks collect post-mortem human brains to foster research into human CNS function and disease. They have been indispensable for uncovering the secrets of many diseases, including Alzheimer's and Parkinson's. At a time when there are so many open questions in neuroscience and the incidence of brain diseases continues to increase in parallel with the aging of the population, brain banking remains at the heart of brain research. However, the major source of brain banks, the clinical autopsy, is rapidly falling into limbo. New strategies, including donor programmes, medico-legal autopsies and banking in networks, as well as fresh considerations of the ethics and public relations, are required.

  20. [Survival of the fattest: the key to human brain evolution].

    Science.gov (United States)

    Cunnane, Stephen C

    2006-01-01

    The circumstances of human brain evolution are of central importance to accounting for human origins, yet are still poorly understood. Human evolution is usually portrayed as having occurred in a hot, dry climate in East Africa where the earliest human ancestors became bipedal and evolved tool-making skills and language while struggling to survive in a wooded or savannah environment. At least three points need to be recognised when constructing concepts of human brain evolution : (1) The human brain cannot develop normally without a reliable supply of several nutrients, notably docosahexaenoic acid, iodine and iron. (2) At term, the human fetus has about 13 % of body weight as fat, a key form of energy insurance supporting brain development that is not found in other primates. (3) The genome of humans and chimpanzees is human brain become so much larger, and how was its present-day nutritional vulnerability circumvented during 5-6 million years of hominid evolution ? The abundant presence of fish bones and shellfish remains in many African hominid fossil sites dating to 2 million years ago implies human ancestors commonly inhabited the shores, but this point is usually overlooked in conceptualizing how the human brain evolved. Shellfish, fish and shore-based animals and plants are the richest dietary sources of the key nutrients needed by the brain. Whether on the shores of lakes, marshes, rivers or the sea, the consumption of most shore-based foods requires no specialized skills or tools. The presence of key brain nutrients and a rich energy supply in shore-based foods would have provided the essential metabolic and nutritional support needed to gradually expand the hominid brain. Abundant availability of these foods also provided the time needed to develop and refine proto-human attributes that subsequently formed the basis of language, culture, tool making and hunting. The presence of body fat in human babies appears to be the product of a long period of

  1. Common genetic variants influence human subcortical brain structures

    OpenAIRE

    Hibar, Derrek P; Stein, Jason L; Renteria, Miguel E; Arias-Vasquez, Alejandro; Desrivières, Sylvane; Jahanshad, Neda; Toro, Roberto; Wittfeld, Katharina; Abramovic, Lucija; Andersson, Micael; Aribisala, Benjamin S; Armstrong, Nicola J; Bernard, Manon; Bohlken, Marc M; Boks, Marco P

    2015-01-01

    The highly complex structure of the human brain is strongly shaped by genetic influences. Subcortical brain regions form circuits with cortical areas to coordinate movement, learning, memory and motivation, and altered circuits can lead to abnormal behaviour and disease. To investigate how common genetic variants affect the structure of these brain regions, here we conduct genome-wide association studies of the volumes of seven subcortical regions and the intracranial volume derived from magn...

  2. Cell diversity and network dynamics in photosensitive human brain organoids

    Science.gov (United States)

    Quadrato, Giorgia; Nguyen, Tuan; Macosko, Evan Z.; Sherwood, John L.; Yang, Sung Min; Berger, Daniel; Maria, Natalie; Scholvin, Jorg; Goldman, Melissa; Kinney, Justin; Boyden, Edward S.; Lichtman, Jeff; Williams, Ziv M.; McCarroll, Steven A.; Arlotta, Paola

    2017-01-01

    In vitro models of the developing brain such as 3D brain organoids offer an unprecedented opportunity to study aspects of human brain development and disease. However, it remains undefined what cells are generated within organoids and to what extent they recapitulate the regional complexity, cellular diversity, and circuit functionality of the brain. Here, we analyzed gene expression in over 80,000 individual cells isolated from 31 human brain organoids. We find that organoids can generate a broad diversity of cells, which are related to endogenous classes, including cells from the cerebral cortex and the retina. Organoids could be developed over extended periods (over 9 months) enabling unprecedented levels of maturity including the formation of dendritic spines and of spontaneously-active neuronal networks. Finally, neuronal activity within organoids could be controlled using light stimulation of photoreceptor-like cells, which may offer ways to probe the functionality of human neuronal circuits using physiological sensory stimuli. PMID:28445462

  3. Impact of Human like Cues on Human Trust in Machines: Brain Imaging and Modeling Studies for Human-Machine Interactions

    Science.gov (United States)

    2018-01-05

    AFRL-AFOSR-JP-TR-2018-0006 Impact of Human like Cues on Human Trust in Machines: Brain Imaging and Modeling Studies for Human -Machine Interactions...AND SUBTITLE Impact of Human like Cues on Human Trust in Machines: Brain Imaging and Modeling Studies for Human -Machine Interactions 5a.  CONTRACT...DISTRIBUTION UNLIMITED: PB Public Release 13. SUPPLEMENTARY NOTES 14. ABSTRACT When a human and an intelligent machine work together as a team, human

  4. Metabolic costs and evolutionary implications of human brain development

    Science.gov (United States)

    Kuzawa, Christopher W.; Chugani, Harry T.; Grossman, Lawrence I.; Lipovich, Leonard; Muzik, Otto; Hof, Patrick R.; Wildman, Derek E.; Sherwood, Chet C.; Leonard, William R.; Lange, Nicholas

    2014-01-01

    The high energetic costs of human brain development have been hypothesized to explain distinctive human traits, including exceptionally slow and protracted preadult growth. Although widely assumed to constrain life-history evolution, the metabolic requirements of the growing human brain are unknown. We combined previously collected PET and MRI data to calculate the human brain’s glucose use from birth to adulthood, which we compare with body growth rate. We evaluate the strength of brain–body metabolic trade-offs using the ratios of brain glucose uptake to the body’s resting metabolic rate (RMR) and daily energy requirements (DER) expressed in glucose-gram equivalents (glucosermr% and glucoseder%). We find that glucosermr% and glucoseder% do not peak at birth (52.5% and 59.8% of RMR, or 35.4% and 38.7% of DER, for males and females, respectively), when relative brain size is largest, but rather in childhood (66.3% and 65.0% of RMR and 43.3% and 43.8% of DER). Body-weight growth (dw/dt) and both glucosermr% and glucoseder% are strongly, inversely related: soon after birth, increases in brain glucose demand are accompanied by proportionate decreases in dw/dt. Ages of peak brain glucose demand and lowest dw/dt co-occur and subsequent developmental declines in brain metabolism are matched by proportionate increases in dw/dt until puberty. The finding that human brain glucose demands peak during childhood, and evidence that brain metabolism and body growth rate covary inversely across development, support the hypothesis that the high costs of human brain development require compensatory slowing of body growth rate. PMID:25157149

  5. Deep Into the Fibers! Postmortem Diffusion Tensor Imaging in Forensic Radiology.

    OpenAIRE

    Flach, Patricia Mildred; Schroth, Sarah Anna; Schweitzer, Wolf; Ampanozi, Garyfalia; Slotboom, Johannes; Kiefer, Claus; Germerott, Tanja; Thali, Michael J; El-Koussy, Marwan

    2015-01-01

    PURPOSE In traumatic brain injury, diffusion-weighted and diffusion tensor imaging of the brain are essential techniques for determining the pathology sustained and the outcome. Postmortem cross-sectional imaging is an established adjunct to forensic autopsy in death investigation. The purpose of this prospective study was to evaluate postmortem diffusion tensor imaging in forensics for its feasibility, influencing factors and correlation to the cause of death compared with autopsy. M...

  6. A Jones matrix formalism for simulating three-dimensional polarized light imaging of brain tissue

    NARCIS (Netherlands)

    Menzel, M.; Michielsen, K.; De Raedt, H.; Reckfort, J.; Amunts, K.; Axer, M.

    2015-01-01

    The neuroimaging technique three-dimensional polarized light imaging (3D-PLI) provides a high-resolution reconstruction of nerve fibres in human post-mortem brains. The orientations of the fibres are derived from birefringence measurements of histological brain sections assuming that the nerve

  7. An anatomically comprehensive atlas of the adult human brain transcriptome

    NARCIS (Netherlands)

    Hawrylycz, M.J.; Beckmann, Christian

    2012-01-01

    Neuroanatomically precise, genome-wide maps of transcript distributions are critical resources to complement genomic sequence data and to correlate functional and genetic brain architecture. Here we describe the generation and analysis of a transcriptional atlas of the adult human brain, comprising

  8. Common genetic variants influence human subcortical brain structures

    NARCIS (Netherlands)

    Hibar, Derrek P.; Stein, Jason L.; Renteria, Miguel E.; Arias-Vasquez, Alejandro; Desrivieres, Sylvane; Jahanshad, Neda; Toro, Roberto; Wittfeld, Katharina; Abramovic, Lucija; Andersson, Micael; Aribisala, Benjamin S.; Armstrong, Nicola J.; Bernard, Manon; Bohlken, Marc M.; Boks, Marco P.; Bralten, Janita; Brown, Andrew A.; Chakravarty, M. Mallar; Chen, Qiang; Ching, Christopher R. K.; Cuellar-Partida, Gabriel; den Braber, Anouk; Giddaluru, Sudheer; Goldman, Aaron L.; Grimm, Oliver; Guadalupe, Tulio; Hass, Johanna; Woldehawariat, Girma; Holmes, Avram J.; Hoogman, Martine; Janowitz, Deborah; Jia, Tianye; Kim, Sungeun; Klein, Marieke; Kraemer, Bernd; Lee, Phil H.; Loohuis, Loes M. Olde; Luciano, Michelle; Macare, Christine; Mather, Karen A.; Mattheisen, Manuel; Milaneschi, Yuri; Nho, Kwangsik; Papmeyer, Martina; Ramasamy, Adaikalavan; Risacher, Shannon L.; Roiz-Santianez, Roberto; Rose, Emma J.; Salami, Alireza; Saemann, Philipp G.; Schmaal, Lianne; Schork, Andrew J.; Shin, Jean; Strike, Lachlan T.; Teumer, Alexander; van Donkelaar, Marjolein M. J.; van Eijk, Kristel R.; Walters, Raymond K.; Westlye, Lars T.; Whelan, Christopher D.; Winkler, Anderson M.; Zwiers, Marcel P.; Alhusaini, Saud; Athanasiu, Lavinia; Ehrlich, Stefan; Hakobjan, Marina M. H.; Hartberg, Cecilie B.; Haukvik, Unn K.; Heister, Angelien J. G. A. M.; Hoehn, David; Kasperaviciute, Dalia; Liewald, David C. M.; Lopez, Lorna M.; Makkinje, Remco R. R.; Matarin, Mar; Naber, Marlies A. M.; McKay, D. Reese; Needham, Margaret; Nugent, Allison C.; Puetz, Benno; Royle, Natalie A.; Shen, Li; Sprooten, Emma; Trabzuni, Daniah; van der Marel, Saskia S. L.; van Hulzen, Kimm J. E.; Walton, Esther; Wolf, Christiane; Almasy, Laura; Ames, David; Arepalli, Sampath; Assareh, Amelia A.; Bastin, Mark E.; Brodaty, Henry; Bulayeva, Kazima B.; Carless, Melanie A.; Cichon, Sven; Corvin, Aiden; Curran, Joanne E.; Czisch, Michael; de Zubicaray, Greig I.; Dillman, Allissa; Duggirala, Ravi; Dyer, Thomas D.; Erk, Susanne; Fedko, Iryna O.; Ferrucci, Luigi; Foroud, Tatiana M.; Fox, Peter T.; Fukunaga, Masaki; Gibbs, J. Raphael; Goering, Harald H. H.; Green, Robert C.; Guelfi, Sebastian; Hansell, Narelle K.; Hartman, Catharina A.; Hegenscheid, Katrin; Heinz, Andreas; Hernandez, Dena G.; Heslenfeld, Dirk J.; Hoekstra, Pieter J.; Holsboer, Florian; Homuth, Georg; Hottenga, Jouke-Jan; Ikeda, Masashi; Jack, Clifford R.; Jenkinson, Mark; Johnson, Robert; Kanai, Ryota; Keil, Maria; Kent, Jack W.; Kochunov, Peter; Kwok, John B.; Lawrie, Stephen M.; Liu, Xinmin; Longo, Dan L.; McMahon, Katie L.; Meisenzah, Eva; Melle, Ingrid; Mahnke, Sebastian; Montgomery, Grant W.; Mostert, Jeanette C.; Muehleisen, Thomas W.; Nalls, Michael A.; Nichols, Thomas E.; Nilsson, Lars G.; Noethen, Markus M.; Ohi, Kazutaka; Olvera, Rene L.; Perez-Iglesias, Rocio; Pike, G. Bruce; Potkin, Steven G.; Reinvang, Ivar; Reppermund, Simone; Rietschel, Marcella; Romanczuk-Seiferth, Nina; Rosen, Glenn D.; Rujescu, Dan; Schnell, Knut; Schofield, Peter R.; Smith, Colin; Steen, Vidar M.; Sussmann, Jessika E.; Thalamuthu, Anbupalam; Toga, Arthur W.; Traynor, Bryan J.; Troncoso, Juan; Turner, Jessica A.; Valdes Hernandez, Maria C.; van't Ent, Dennis; van der Brug, Marcel; van der Wee, Nic J. A.; van Tol, Marie-Jose; Veltman, Dick J.; Wassink, Thomas H.; Westman, Eric; Zielke, Ronald H.; Zonderman, Alan B.; Ashbrook, David G.; Hager, Reinmar; Lu, Lu; McMahon, Francis J.; Morris, Derek W.; Williams, Robert W.; Brunner, Han G.; Buckner, Randy L.; Buitelaar, Jan K.; Cahn, Wiepke; Calhoun, Vince D.; Cavalleri, Gianpiero L.; Crespo-Facorro, Benedicto; Dale, Anders M.; Davies, Gareth E.; Delanty, Norman; Depondt, Chantal; Djurovic, Srdjan; Drevets, Wayne C.; Espeseth, Thomas; Gollub, Randy L.; Ho, Beng-Choon; Hoffman, Wolfgang; Hosten, Norbert; Kahn, Rene S.; Le Hellard, Stephanie; Meyer-Lindenberg, Andreas; Mueller-Myhsok, Bertram; Nauck, Matthias; Nyberg, Lars; Pandolfo, Massimo; Penninx, Brenda W. J. H.; Roffman, Joshua L.; Sisodiya, Sanjay M.; Smoller, Jordan W.; van Bokhoven, Hans; van Haren, Neeltje E. M.; Voelzke, Henry; Walter, Henrik; Weiner, Michael W.; Wen, Wei; White, Tonya; Agartz, Ingrid; Andreassen, Ole A.; Blangero, John; Boomsma, Dorret I.; Brouwer, Rachel M.; Cannon, Dara M.; Cookson, Mark R.; de Geus, Eco J. C.; Deary, Ian J.; Donohoe, Gary; Fernandez, Guillen; Fisher, Simon E.; Francks, Clyde; Glahn, David C.; Grabe, Hans J.; Gruber, Oliver; Hardy, John; Hashimoto, Ryota; Pol, Hilleke E. Hulshoff; Joensson, Erik G.; Kloszewska, Iwona; Lovestone, Simon; Mattay, Venkata S.; Mecocci, Patrizia; McDonald, Colm; McIntosh, Andrew M.; Ophoff, Roel A.; Paus, Tomas; Pausova, Zdenka; Ryten, Mina; Sachdev, Perminder S.; Saykin, Andrew J.; Simmons, Andy; Singleton, Andrew; Soininen, Hilkka; Wardlaw, Joanna M.; Weale, Michael E.; Weinberger, Daniel R.; Adams, Hieab H. H.; Launer, Lenore J.; Seiler, Stephan; Schmidt, Reinhold; Chauhan, Ganesh; Satizabal, Claudia L.; Becker, James T.; Yanek, Lisa; van der Lee, Sven J.; Ebling, Maritza; Fischl, Bruce; Longstreth, W. T.; Greve, Douglas; Schmidt, Helena; Nyquist, Paul; Vinke, Louis N.; van Duijn, Cornelia M.; Xue, Luting; Mazoyer, Bernard; Bis, Joshua C.; Gudnason, Vilmundur; Seshadri, Sudha; Ikram, M. Arfan; Martin, Nicholas G.; Wright, Margaret J.; Schumann, Gunter; Franke, Barbara; Thompson, Paul M.; Medland, Sarah E.

    2015-01-01

    The highly complex structure of the human brain is strongly shaped by genetic influences(1). Subcortical brain regions form circuits with cortical areas to coordinate movement(2), learning, memory(3) and motivation(4), and altered circuits can lead to abnormal behaviour and disease(5). To

  9. Common genetic variants influence human subcortical brain structures

    NARCIS (Netherlands)

    D.P. Hibar (Derrek); J.L. Stein; M.E. Rentería (Miguel); A. Arias-Vásquez (Alejandro); S. Desrivières (Sylvane); N. Jahanshad (Neda); R. Toro (Roberto); K. Wittfeld (Katharina); L. Abramovic (Lucija); M. Andersson (Micael); B. Aribisala (Benjamin); N.J. Armstrong (Nicola J.); M. Bernard (Manon); M.M. Bohlken (Marc M.); M.P.M. Boks (Marco); L.B.C. Bralten (Linda); A.A. Brown (Andrew); M.M. Chakravarty (M. Mallar); Q. Chen (Qiang); C.R.K. Ching (Christopher); G. Cuellar-Partida (Gabriel); A. den Braber (Anouk); S. Giddaluru (Sudheer); A.L. Goldman (Aaron L.); O. Grimm (Oliver); T. Guadalupe (Tulio); J. Hass (Johanna); G. Woldehawariat (Girma); A.J. Holmes (Avram); M. Hoogman (Martine); D. Janowitz (Deborah); T. Jia (Tianye); S. Kim (Shinseog); M. Klein (Marieke); B. Kraemer (Bernd); P.H. Lee (Phil H.); L.M. Olde Loohuis (Loes M.); M. Luciano (Michelle); C. MacAre (Christine); R. Mather; M. Mattheisen (Manuel); Y. Milaneschi (Yuri); K. Nho (Kwangsik); M. Papmeyer (Martina); A. Ramasamy (Adaikalavan); S.L. Risacher (Shannon); R. Roiz-Santiañez (Roberto); E.J. Rose (Emma); A. Salami (Alireza); P.G. Sämann (Philipp); L. Schmaal (Lianne); N.J. Schork (Nicholas); J. Shin (Jean); V.M. Strike (Vanessa); A. Teumer (Alexander); M.M.J. Van Donkelaar (Marjolein M. J.); K.R. van Eijk (Kristel); R.K. Walters (Raymond); L.T. Westlye (Lars); C.D. Whelan (Christopher); A.M. Winkler (Anderson); M.P. Zwiers (Marcel); S. Alhusaini (Saud); L. Athanasiu (Lavinia); S.M. Ehrlich (Stefan); M. Hakobjan (Marina); C.B. Hartberg (Cecilie B.); U.K. Haukvik (Unn); A.J.G.A.M. Heister (Angelien J. G. A. M.); D. Hoehn (David); D. Kasperaviciute (Dalia); D.C. Liewald (David C.); L.M. Lopez (Lorna); R.R.R. Makkinje (Remco R. R.); M. Matarin (Mar); M.A.M. Naber (Marlies A. M.); D. Reese McKay; M. Needham (Margaret); A.C. Nugent (Allison); B. Pütz (Benno); N.A. Royle (Natalie); L. Shen (Li); R. Sprooten (Roy); D. Trabzuni (Danyah); S.S.L. Van Der Marel (Saskia S. L.); K.J.E. Van Hulzen (Kimm J. E.); E. Walton (Esther); A. Björnsson (Asgeir); L. Almasy (Laura); D.J. Ames (David); S. Arepalli (Sampath); A.A. Assareh; M.E. Bastin (Mark); H. Brodaty (Henry); K. Bulayeva (Kazima); M.A. Carless (Melanie); S. Cichon (Sven); A. Corvin (Aiden); J.E. Curran (Joanne); M. Czisch (Michael); G.I. de Zubicaray (Greig); A. Dillman (Allissa); A. Duggirala (Aparna); M.D. Dyer (Matthew); S. Erk; I. Fedko (Iryna); L. Ferrucci (Luigi); T. Foroud (Tatiana); P.T. Fox (Peter); M. Fukunaga (Masaki); J. Raphael Gibbs; H.H.H. Göring (Harald H.); R.C. Green (Robert C.); S. Guelfi (Sebastian); N.K. Hansell (Narelle); C.A. Hartman (Catharina); K. Hegenscheid (Katrin); J. Heinz (Judith); D.G. Hernandez (Dena); D.J. Heslenfeld (Dirk); P.J. Hoekstra (Pieter); F. Holsboer; G. Homuth (Georg); J.J. Hottenga (Jouke Jan); M. Ikeda (Masashi); C.R. Jack Jr. (Clifford); S. Jenkinson (Sarah); R. Johnson (Robert); R. Kanai (Ryota); M. Keil (Maria); J.W. Kent (Jack W.); P. Kochunov (Peter); J.B. Kwok (John B.); S. Lawrie (Stephen); X. Liu (Xinmin); D.L. Longo (Dan L.); K.L. Mcmahon (Katie); E. Meisenzahl (Eva); I. Melle (Ingrid); S. Mohnke (Sebastian); G.W. Montgomery (Grant); J.C. Mostert (Jeanette C.); T.W. Mühleisen (Thomas); M.A. Nalls (Michael); T.E. Nichols (Thomas); L.G. Nilsson; M.M. Nöthen (Markus); K. Ohi (Kazutaka); R.L. Olvera (Rene); R. Perez-Iglesias (Rocio); G. Bruce Pike; S.G. Potkin (Steven); I. Reinvang (Ivar); S. Reppermund; M. Rietschel (Marcella); N. Seiferth (Nina); G.D. Rosen (Glenn D.); D. Rujescu (Dan); K. Schnell (Kerry); C.J. Schofield (Christopher); C. Smith (Colin); V.M. Steen (Vidar); J. Sussmann (Jessika); A. Thalamuthu (Anbupalam); A.W. Toga (Arthur W.); B. Traynor (Bryan); J.C. Troncoso (Juan); J. Turner (Jessica); M.C. Valdés Hernández (Maria); D. van 't Ent (Dennis); M.P. van der Brug (Marcel); N.J. van der Wee (Nic); M.J.D. van Tol (Marie-José); D.J. Veltman (Dick); A.M.J. Wassink (Annemarie); E. Westman (Eric); R.H. Zielke (Ronald H.); A.B. Zonderman (Alan B.); D.G. Ashbrook (David G.); R. Hager (Reinmar); L. Lu (Lu); F.J. Mcmahon (Francis J); D.W. Morris (Derek W); R.W. Williams (Robert W.); H.G. Brunner; M. Buckner; J.K. Buitelaar (Jan K.); W. Cahn (Wiepke); V.D. Calhoun Vince D. (V.); G. Cavalleri (Gianpiero); B. Crespo-Facorro (Benedicto); A.M. Dale (Anders); G.E. Davies (Gareth); N. Delanty; C. Depondt (Chantal); S. Djurovic (Srdjan); D.A. Drevets (Douglas); T. Espeseth (Thomas); R.L. Gollub (Randy); B.C. Ho (Beng ); W. Hoffmann (Wolfgang); N. Hosten (Norbert); R. Kahn (René); S. Le Hellard (Stephanie); A. Meyer-Lindenberg; B. Müller-Myhsok (B.); M. Nauck (Matthias); L. Nyberg (Lars); M. Pandolfo (Massimo); B.W.J.H. Penninx (Brenda); J.L. Roffman (Joshua); S.M. Sisodiya (Sanjay); J.W. Smoller; H. van Bokhoven (Hans); N.E.M. van Haren (Neeltje E.); H. Völzke (Henry); H.J. Walter (Henrik); M.W. Weiner (Michael); W. Wen (Wei); T.J.H. White (Tonya); I. Agartz (Ingrid); O.A. Andreassen (Ole); J. Blangero (John); D.I. Boomsma (Dorret); R.M. Brouwer (Rachel); D.M. Cannon (Dara); M.R. Cookson (Mark); E.J.C. de Geus (Eco); I.J. Deary (Ian J.); D.J. Donohoe (Dennis); G. Fernandez (Guillén); S.E. Fisher (Simon); C. Francks (Clyde); D.C. Glahn (David); H.J. Grabe (Hans Jörgen); O. Gruber (Oliver); J. Hardy (John); R. Hashimoto (Ryota); H.E. Hulshoff Pol (Hilleke); E.G. Jönsson (Erik); I. Kloszewska (Iwona); S. Lovestone (Simon); V.S. Mattay (Venkata S.); P. Mecocci (Patrizia); C. McDonald (Colm); A.M. McIntosh (Andrew); R.A. Ophoff (Roel); T. Paus (Tomas); Z. Pausova (Zdenka); M. Ryten (Mina); P.S. Sachdev (Perminder); A.J. Saykin (Andrew); A. Simmons (Andrew); A. Singleton (Andrew); H. Soininen (H.); J.M. Wardlaw (J.); M.E. Weale (Michael); D.R. Weinberger (Daniel); H.H.H. Adams (Hieab); L.J. Launer (Lenore); S. Seiler (Stephan); R. Schmidt (Reinhold); G. Chauhan (Ganesh); C.L. Satizabal (Claudia L.); J.T. Becker (James); L.R. Yanek (Lisa); S.J. van der Lee (Sven); M. Ebling (Maritza); B. Fischl (Bruce); W.T. Longstreth Jr; D. Greve (Douglas); R. Schmidt (Reinhold); P. Nyquist (Paul); L.N. Vinke (Louis N.); C.M. van Duijn (Cornelia); L. Xue (Luting); B. Mazoyer (Bernard); J.C. Bis (Joshua); V. Gudnason (Vilmundur); S. Seshadri (Sudha); M.A. Ikram (Arfan); N.G. Martin (Nicholas); M.J. Wright (Margaret); G. Schumann (Gunter); B. Franke (Barbara); P.M. Thompson (Paul); S.E. Medland (Sarah Elizabeth)

    2015-01-01

    textabstractThe highly complex structure of the human brain is strongly shaped by genetic influences. Subcortical brain regions form circuits with cortical areas to coordinate movement, learning, memory and motivation, and altered circuits can lead to abnormal behaviour and disease. To investigate

  10. Genetic contributions to human brain morphology and intelligence

    NARCIS (Netherlands)

    Hulshoff Pol, H.E.; Schnack, H.G.; Posthuma, D.; Mandl, R.C.W.; Baaré, W.F.; van Oel, C.J.; van Haren, N.E.M.; Colins, D.L.; Evans, A.C.; Amunts, K.; Bürgel, U.; Zilles, K.; de Geus, E.J.C.; Boomsma, D.I.; Kahn, R.S.

    2006-01-01

    Variation in gray matter (GM) and white matter (WM) volume of the adult human brain is primarily genetically determined. Moreover, total brain volume is positively correlated with general intelligence, and both share a common genetic origin. However, although genetic effects on morphology of

  11. Genetic contributions to human brain morphology and intelligence

    DEFF Research Database (Denmark)

    Hulshoff Pol, HE; Schnack, HG; Posthuma, D

    2006-01-01

    Variation in gray matter (GM) and white matter (WM) volume of the adult human brain is primarily genetically determined. Moreover, total brain volume is positively correlated with general intelligence, and both share a common genetic origin. However, although genetic effects on morphology of spec...

  12. Deep Into the Fibers! Postmortem Diffusion Tensor Imaging in Forensic Radiology.

    Science.gov (United States)

    Flach, Patricia Mildred; Schroth, Sarah; Schweitzer, Wolf; Ampanozi, Garyfalia; Slotboom, Johannes; Kiefer, Claus; Germerott, Tanja; Thali, Michael J; El-Koussy, Marwan

    2015-09-01

    In traumatic brain injury, diffusion-weighted and diffusion tensor imaging of the brain are essential techniques for determining the pathology sustained and the outcome. Postmortem cross-sectional imaging is an established adjunct to forensic autopsy in death investigation. The purpose of this prospective study was to evaluate postmortem diffusion tensor imaging in forensics for its feasibility, influencing factors and correlation to the cause of death compared with autopsy. Postmortem computed tomography, magnetic resonance imaging, and diffusion tensor imaging with fiber tracking were performed in 10 deceased subjects. The Likert scale grading of colored fractional anisotropy maps was correlated to the body temperature and intracranial pathology to assess the diagnostic feasibility of postmortem diffusion tensor imaging and fiber tracking. Optimal fiber tracking (>15,000 fiber tracts) was achieved with a body temperature at 10°C. Likert scale grading showed no linear correlation (P > 0.7) to fiber tract counts. No statistically significant correlation between total fiber count and postmortem interval could be observed (P = 0.122). Postmortem diffusion tensor imaging and fiber tracking allowed for radiological diagnosis in cases with shearing injuries but was impaired in cases with pneumencephalon and intracerebral mass hemorrhage. Postmortem diffusion tensor imaging with fiber tracking provides an exceptional in situ insight "deep into the fibers" of the brain with diagnostic benefit in traumatic brain injury and axonal injuries in the assessment of the underlying cause of death, considering influencing factors for optimal imaging technique.

  13. Toward discovery science of human brain function.

    Science.gov (United States)

    Biswal, Bharat B; Mennes, Maarten; Zuo, Xi-Nian; Gohel, Suril; Kelly, Clare; Smith, Steve M; Beckmann, Christian F; Adelstein, Jonathan S; Buckner, Randy L; Colcombe, Stan; Dogonowski, Anne-Marie; Ernst, Monique; Fair, Damien; Hampson, Michelle; Hoptman, Matthew J; Hyde, James S; Kiviniemi, Vesa J; Kötter, Rolf; Li, Shi-Jiang; Lin, Ching-Po; Lowe, Mark J; Mackay, Clare; Madden, David J; Madsen, Kristoffer H; Margulies, Daniel S; Mayberg, Helen S; McMahon, Katie; Monk, Christopher S; Mostofsky, Stewart H; Nagel, Bonnie J; Pekar, James J; Peltier, Scott J; Petersen, Steven E; Riedl, Valentin; Rombouts, Serge A R B; Rypma, Bart; Schlaggar, Bradley L; Schmidt, Sein; Seidler, Rachael D; Siegle, Greg J; Sorg, Christian; Teng, Gao-Jun; Veijola, Juha; Villringer, Arno; Walter, Martin; Wang, Lihong; Weng, Xu-Chu; Whitfield-Gabrieli, Susan; Williamson, Peter; Windischberger, Christian; Zang, Yu-Feng; Zhang, Hong-Ying; Castellanos, F Xavier; Milham, Michael P

    2010-03-09

    Although it is being successfully implemented for exploration of the genome, discovery science has eluded the functional neuroimaging community. The core challenge remains the development of common paradigms for interrogating the myriad functional systems in the brain without the constraints of a priori hypotheses. Resting-state functional MRI (R-fMRI) constitutes a candidate approach capable of addressing this challenge. Imaging the brain during rest reveals large-amplitude spontaneous low-frequency (science of brain function, the 1000 Functional Connectomes Project dataset is freely accessible at www.nitrc.org/projects/fcon_1000/.

  14. Isolation of Borna Disease Virus from Human Brain Tissue

    Science.gov (United States)

    Nakamura, Yurie; Takahashi, Hirokazu; Shoya, Yuko; Nakaya, Takaaki; Watanabe, Makiko; Tomonaga, Keizo; Iwahashi, Kazuhiko; Ameno, Kiyoshi; Momiyama, Noriko; Taniyama, Hiroyuka; Sata, Tetsutaro; Kurata, Takeshi; de la Torre, Juan Carlos; Ikuta, Kazuyoshi

    2000-01-01

    Serological and molecular epidemiological studies indicate that Borna disease virus (BDV) can infect humans and is possibly associated with certain neuropsychiatric disorders. We examined brain tissue collected at autopsy from four schizophrenic patients and two healthy controls for the presence of BDV markers in 12 different brain regions. BDV RNA and antigen was detected in four brain regions of a BDV-seropositive schizophrenic patient (P2) with a very recent (2 years) onset of disease. BDV markers exhibited a regionally localized distribution. BDV RNA was found in newborn Mongolian gerbils intracranially inoculated with homogenates from BDV-positive brain regions of P2. Human oligodendroglia (OL) cells inoculated with brain homogenates from BDV-positive gerbils allowed propagation and isolation of BDVHuP2br, a human brain-derived BDV. Virus isolation was also possible by transfection of Vero cells with ribonucleoprotein complexes prepared from BDV-positive human and gerbil brain tissues. BDVHuP2br was genetically closely related to but distinct from previously reported human- and animal-derived BDV sequences. PMID:10775596

  15. Sex beyond the genitalia: The human brain mosaic

    Science.gov (United States)

    Joel, Daphna; Berman, Zohar; Tavor, Ido; Wexler, Nadav; Gaber, Olga; Stein, Yaniv; Shefi, Nisan; Pool, Jared; Urchs, Sebastian; Margulies, Daniel S.; Liem, Franziskus; Hänggi, Jürgen; Jäncke, Lutz; Assaf, Yaniv

    2015-01-01

    Whereas a categorical difference in the genitals has always been acknowledged, the question of how far these categories extend into human biology is still not resolved. Documented sex/gender differences in the brain are often taken as support of a sexually dimorphic view of human brains (“female brain” or “male brain”). However, such a distinction would be possible only if sex/gender differences in brain features were highly dimorphic (i.e., little overlap between the forms of these features in males and females) and internally consistent (i.e., a brain has only “male” or only “female” features). Here, analysis of MRIs of more than 1,400 human brains from four datasets reveals extensive overlap between the distributions of females and males for all gray matter, white matter, and connections assessed. Moreover, analyses of internal consistency reveal that brains with features that are consistently at one end of the “maleness-femaleness” continuum are rare. Rather, most brains are comprised of unique “mosaics” of features, some more common in females compared with males, some more common in males compared with females, and some common in both females and males. Our findings are robust across sample, age, type of MRI, and method of analysis. These findings are corroborated by a similar analysis of personality traits, attitudes, interests, and behaviors of more than 5,500 individuals, which reveals that internal consistency is extremely rare. Our study demonstrates that, although there are sex/gender differences in the brain, human brains do not belong to one of two distinct categories: male brain/female brain. PMID:26621705

  16. Quantitation of glial fibrillary acidic protein in human brain tumours

    DEFF Research Database (Denmark)

    Rasmussen, S; Bock, E; Warecka, K

    1980-01-01

    The glial fibrillary acidic protein (GFA) content of 58 human brain tumours was determined by quantitative immunoelectrophoresis, using monospecific antibody against GFA. Astrocytomas, glioblastomas, oligodendrogliomas, spongioblastomas, ependymomas and medulloblastomas contained relatively high...... amounts of GFA, up to 85 times the concentration in parietal grey substance of normal human brain. GFA was not found in neurinomas, meningiomas, adenomas of the hypophysis, or in a single case of metastasis of adenocarcinoma. Non-glial tumours of craniopharyngioma and haemangioblastoma were infiltrated...

  17. Optogenetic control of human neurons in organotypic brain cultures

    DEFF Research Database (Denmark)

    Andersson, My; Avaliani, Natalia; Svensson, Andreas

    2016-01-01

    Optogenetics is one of the most powerful tools in neuroscience, allowing for selective control of specific neuronal populations in the brain of experimental animals, including mammals. We report, for the first time, the application of optogenetic tools to human brain tissue providing a proof......-of-concept for the use of optogenetics in neuromodulation of human cortical and hippocampal neurons as a possible tool to explore network mechanisms and develop future therapeutic strategies....

  18. Centrality of Social Interaction in Human Brain Function.

    Science.gov (United States)

    Hari, Riitta; Henriksson, Linda; Malinen, Sanna; Parkkonen, Lauri

    2015-10-07

    People are embedded in social interaction that shapes their brains throughout lifetime. Instead of emerging from lower-level cognitive functions, social interaction could be the default mode via which humans communicate with their environment. Should this hypothesis be true, it would have profound implications on how we think about brain functions and how we dissect and simulate them. We suggest that the research on the brain basis of social cognition and interaction should move from passive spectator science to studies including engaged participants and simultaneous recordings from the brains of the interacting persons. Copyright © 2015 Elsevier Inc. All rights reserved.

  19. Outer brain barriers in rat and human development

    DEFF Research Database (Denmark)

    Brøchner, Christian B; Holst, Camilla Bjørnbak; Møllgård, Kjeld

    2015-01-01

    Complex barriers at the brain's surface, particularly in development, are poorly defined. In the adult, arachnoid blood-cerebrospinal fluid (CSF) barrier separates the fenestrated dural vessels from the CSF by means of a cell layer joined by tight junctions. Outer CSF-brain barrier provides...... diffusion restriction between brain and subarachnoid CSF through an initial radial glial end feet layer covered with a pial surface layer. To further characterize these interfaces we examined embryonic rat brains from E10 to P0 and forebrains from human embryos and fetuses (6-21st weeks post...

  20. Exploring terra incognita of cognitive science: Lateralization of gene expression at the frontal pole of the human brain

    Directory of Open Access Journals (Sweden)

    Dolina I.A.

    2017-09-01

    Full Text Available Background. Rostral prefrontal cortex, or frontopolar cortex (FPC, also known as Brodmann area 10 (BA10, is the most anterior part of the human brain. It is one of the largest cytoarchitectonic areas of the human brain that has significantly increased its volume during evolution. Anatomically the le (BA10L and right (BA10R parts of FPC show slight asymmetries and they may have distinctive cognitive functions. Objective. In the present study, we investigated differential expression of the transcriptome in the le and right parts of BA10. Design. Postmortem samples of human brain tissue from fourteen donors (male/ female without history of psychiatric and neurological diseases, mean age 39.79±3.23 years old, mean postmortem interval 12.10±1.76 h were obtained using the resources of three institutions: the Partner Institute of Computational Biology of Chinese Academy of Sciences, the Max Planck Institute for Evolutionary Anthropology, and NIH Neuro-BioBank. Results. By using a standard RNA-sequencing followed by bioinformatic analysis, we identified 61 genes with differential expression in the le and right FPC. In general, gene expression was increased in BA10R relative to BA10L: 40 vs. 21 genes, respectively. According to gene ontology analysis, the majority of up-regulated genes in BA10R be- longed to the protein-coding category, whereas protein-coding and non-coding genes were equally up-expressed in BA10L. Most of the up-regulated genes in BA10R were involved in brain plasticity and activity-dependent mechanisms also known for their role in the hippocampus. 24 out of 30 mental disorder-related genes in the dataset were disrupted in schizophrenia. No such a wide association with other mental disorders was found. Conclusion. Discovered differences point at possible causes of hemispheric asymmetries in the human frontal lobes and at the molecular base of higher-order cognitive processes in health and disease.

  1. Modern human brain growth and development. Contribution to brain evolution in hominids

    OpenAIRE

    Ventrice, F

    2011-01-01

    Human phylogenetic history is directly related to brain evolution. But many biologic processes related to the appearance of this complex organ are unknown, mainly due to the fact that it is an organ composed of soft tissue, which is not sensitive to the fossilization processes. Hence, to infer human brain evolution it is essential to study the indirect evidences it leaves in the cranial bones, such as the endocranial size (cranial capacity) and shape. In this sense, the hominid fossil record ...

  2. Sexual orientation and the size of the anterior commissure in the human brain.

    OpenAIRE

    Allen, L S; Gorski, R A

    1992-01-01

    The anterior commissure, a fiber tract that is larger in its midsagittal area in women than in men, was examined in 90 postmortem brains from homosexual men, heterosexual men, and heterosexual women. The midsagittal plane of the anterior commissure in homosexual men was 18% larger than in heterosexual women and 34% larger than in heterosexual men. This anatomical difference, which correlates with gender and sexual orientation, may, in part, underlie differences in cognitive function and cereb...

  3. Toward an integrative science of the developing human mind and brain: Focus on the developing cortex ?

    OpenAIRE

    Jernigan, Terry L.; Brown, Timothy T.; Bartsch, Hauke; Dale, Anders M.

    2015-01-01

    © 2015 The Authors. Based on the Huttenlocher lecture, this article describes the need for a more integrative scientific paradigm for addressing important questions raised by key observations made over 2 decades ago. Among these are the early descriptions by Huttenlocher of variability in synaptic density in cortex of postmortem brains of children of different ages and the almost simultaneous reports of cortical volume reductions on MR imaging in children and adolescents. In spite of much pro...

  4. Estimating Neural Signal Dynamics in the Human Brain

    Directory of Open Access Journals (Sweden)

    Christopher W Tyler

    2011-06-01

    Full Text Available Although brain imaging methods are highly effective for localizing the effects of neural activation throughout the human brain in terms of the blood oxygenation level dependent (BOLD response, there is currently no way to estimate the underlying neural signal dynamics in generating the BOLD response in each local activation region (except for processes slower than the BOLD time course. Knowledge of the neural signal is critical information if spatial mapping is to progress to the analysis of dynamic information flow through the cortical networks as the brain performs its tasks. We introduce an analytic approach that provides a new level of conceptualization and specificity in the study of brain processing by noninvasive methods. This technique allows us to use brain imaging methods to determine the dynamics of local neural population responses to their native temporal resolution throughout the human brain, with relatively narrow confidence intervals on many response properties. The ability to characterize local neural dynamics in the human brain represents a significant enhancement of brain imaging capabilities, with potential application from general cognitive studies to assessment of neuropathologies.

  5. Quantitative assessments of traumatic axonal injury in human brain: concordance of microdialysis and advanced MRI.

    Science.gov (United States)

    Magnoni, Sandra; Mac Donald, Christine L; Esparza, Thomas J; Conte, Valeria; Sorrell, James; Macrì, Mario; Bertani, Giulio; Biffi, Riccardo; Costa, Antonella; Sammons, Brian; Snyder, Abraham Z; Shimony, Joshua S; Triulzi, Fabio; Stocchetti, Nino; Brody, David L

    2015-08-01

    regions. We interpret this result to mean that both microdialysis and diffusion tensor magnetic resonance imaging accurately reflect the same pathophysiological process: traumatic axonal injury. This cross-validation increases confidence in both methods for the clinical assessment of axonal injury. However, neither microdialysis nor diffusion tensor magnetic resonance imaging have been validated versus post-mortem histology in humans. Furthermore, future work will be required to determine the prognostic significance of these assessments of traumatic axonal injury when combined with other clinical and radiological measures. © The Author (2015). Published by Oxford University Press on behalf of the Guarantors of Brain. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

  6. Plastination of dissected brain specimens and Mulligan-stained sections of the human brain.

    Science.gov (United States)

    Baeres, F M; Møller, M

    2001-12-01

    The difficulties in obtaining human brain material for teaching neuroanatomy have increased the demand for more durable brain specimens. In this paper, we describe results obtained by preparing large, plastinated, dissected human brain specimens and Mulligan-stained sections of the human brain. The brains were fixed in formalin, washed and dissected in order to visualize the fibre tracts and larger nuclei in the central nervous system. This was followed by dehydration at -20 degrees C in acetone. The specimens were then impregnated with silicone, Biodur S10, in vacuo and hardened in Biodur S6 vapour. The grey and white substance in the central nervous system as well as the larger fibre tracts and nuclei were clearly visible in the dissected, plastinated specimens. Coronal and sagittal sections of the human brain were stained according to Tompsett's modification of the Mulligan method. The sections were then dehydrated in cold acetone followed by forced impregnation with Biodur S10 and hardening. The plastinated sections stained distinctly and strongly and the nuclei in the forebrain, cerebellum and brain stem could be identified easily. The sections did not fade when exposed to light and could be easily handled in the classroom without damage. Therefore, the distinct visualization of neuroanatomical structures, the improved durability of the specimens, as well as the lack of odour make plastinated specimens and stained sections of the central nervous system a valuable tool for teaching neuroanatomy that compliments the use of wet preparations.

  7. Conscious brain-to-brain communication in humans using non-invasive technologies.

    Science.gov (United States)

    Grau, Carles; Ginhoux, Romuald; Riera, Alejandro; Nguyen, Thanh Lam; Chauvat, Hubert; Berg, Michel; Amengual, Julià L; Pascual-Leone, Alvaro; Ruffini, Giulio

    2014-01-01

    Human sensory and motor systems provide the natural means for the exchange of information between individuals, and, hence, the basis for human civilization. The recent development of brain-computer interfaces (BCI) has provided an important element for the creation of brain-to-brain communication systems, and precise brain stimulation techniques are now available for the realization of non-invasive computer-brain interfaces (CBI). These technologies, BCI and CBI, can be combined to realize the vision of non-invasive, computer-mediated brain-to-brain (B2B) communication between subjects (hyperinteraction). Here we demonstrate the conscious transmission of information between human brains through the intact scalp and without intervention of motor or peripheral sensory systems. Pseudo-random binary streams encoding words were transmitted between the minds of emitter and receiver subjects separated by great distances, representing the realization of the first human brain-to-brain interface. In a series of experiments, we established internet-mediated B2B communication by combining a BCI based on voluntary motor imagery-controlled electroencephalographic (EEG) changes with a CBI inducing the conscious perception of phosphenes (light flashes) through neuronavigated, robotized transcranial magnetic stimulation (TMS), with special care taken to block sensory (tactile, visual or auditory) cues. Our results provide a critical proof-of-principle demonstration for the development of conscious B2B communication technologies. More fully developed, related implementations will open new research venues in cognitive, social and clinical neuroscience and the scientific study of consciousness. We envision that hyperinteraction technologies will eventually have a profound impact on the social structure of our civilization and raise important ethical issues.

  8. Conscious brain-to-brain communication in humans using non-invasive technologies.

    Directory of Open Access Journals (Sweden)

    Carles Grau

    Full Text Available Human sensory and motor systems provide the natural means for the exchange of information between individuals, and, hence, the basis for human civilization. The recent development of brain-computer interfaces (BCI has provided an important element for the creation of brain-to-brain communication systems, and precise brain stimulation techniques are now available for the realization of non-invasive computer-brain interfaces (CBI. These technologies, BCI and CBI, can be combined to realize the vision of non-invasive, computer-mediated brain-to-brain (B2B communication between subjects (hyperinteraction. Here we demonstrate the conscious transmission of information between human brains through the intact scalp and without intervention of motor or peripheral sensory systems. Pseudo-random binary streams encoding words were transmitted between the minds of emitter and receiver subjects separated by great distances, representing the realization of the first human brain-to-brain interface. In a series of experiments, we established internet-mediated B2B communication by combining a BCI based on voluntary motor imagery-controlled electroencephalographic (EEG changes with a CBI inducing the conscious perception of phosphenes (light flashes through neuronavigated, robotized transcranial magnetic stimulation (TMS, with special care taken to block sensory (tactile, visual or auditory cues. Our results provide a critical proof-of-principle demonstration for the development of conscious B2B communication technologies. More fully developed, related implementations will open new research venues in cognitive, social and clinical neuroscience and the scientific study of consciousness. We envision that hyperinteraction technologies will eventually have a profound impact on the social structure of our civilization and raise important ethical issues.

  9. Optogenetic control of human neurons in organotypic brain cultures

    DEFF Research Database (Denmark)

    Andersson, My; Avaliani, Natalia; Svensson, Andreas

    2016-01-01

    Optogenetics is one of the most powerful tools in neuroscience, allowing for selective control of specific neuronal populations in the brain of experimental animals, including mammals. We report, for the first time, the application of optogenetic tools to human brain tissue providing a proof-of-c......-of-concept for the use of optogenetics in neuromodulation of human cortical and hippocampal neurons as a possible tool to explore network mechanisms and develop future therapeutic strategies.......Optogenetics is one of the most powerful tools in neuroscience, allowing for selective control of specific neuronal populations in the brain of experimental animals, including mammals. We report, for the first time, the application of optogenetic tools to human brain tissue providing a proof...

  10. DNA and RNA analysis of blood and muscle from bodies with variable postmortem intervals

    DEFF Research Database (Denmark)

    Hansen, Jakob; Lesnikova, Iana; Funder, Anette Mariane Daa

    2014-01-01

    The breakdown of DNA and RNA in decomposing human tissue represents a major obstacle for postmortem forensic molecular analysis. This study investigated the feasibility of performing PCR-based molecular analysis of blood and muscle tissue from 45 autopsy cases with defined postmortem intervals......) DNA fragments from all samples with postmortem intervals below 3 days whereas 400-600 bp long fragments typically could be amplified from the most decomposed muscle specimens. RNA was less stable than DNA in postmortem muscle tissue, yet selected mRNA molecules could be detected by reverse......-transcriptase PCR in all samples up to 3 days after death. We conclude that analysis of DNA from bodies with a wide postmortem interval range is usually possible whereas the consistency of RNA analyses decreases considerably 3 days postmortem. We showed that muscle tissue is a highly usable source of DNA and RNA...

  11. Lactate fuels the human brain during exercise

    DEFF Research Database (Denmark)

    Quistorff, Bjørn; Secher, Niels H; Van Lieshout, Johannes J

    2008-01-01

    lactate in proportion to the arterial concentration. Cerebral lactate uptake, together with glucose uptake, is larger than the uptake accounted for by the concomitant O(2) uptake, as reflected by the decrease in cerebral metabolic ratio (CMR) [the cerebral molar uptake ratio O(2)/(glucose+(1/2) lactate...... blockade but not with beta(1)-adrenergic blockade alone. Also, CMR decreases in response to epinephrine, suggesting that a beta(2)-adrenergic receptor mechanism enhances glucose and perhaps lactate transport across the blood-brain barrier. The pattern of CMR decrease under various forms of brain activation...

  12. Human Development XII: A Theory for the Structure and Function of the Human Brain

    OpenAIRE

    Søren Ventegodt; Tyge Dahl Hermansen; Isack Kandel; Joav Merrick

    2008-01-01

    The human brain is probably the most complicated single structure in the biological universe. The cerebral cortex that is traditionally connected with consciousness is extremely complex. The brain contains approximately 1,000,000 km of nerve fibers, indicating its enormous complexity and which makes it difficult for scientists to reveal the function of the brain. In this paper, we propose a new model for brain functions, i.e., information-guided self-organization of neural patterns, where inf...

  13. Toward discovery science of human brain function.

    NARCIS (Netherlands)

    Biswal, B.B.; Mennes, M.J.J.; Zuo, X.N.; Gohel, S.; Kelly, C.; Smith, S.M.; Beckmann, C.F.; Adelstein, J.S.; Buckner, R.L.; Colcombe, S.; Dogonowski, A.M.; Ernst, M.; Fair, D.; Hampson, M.; Hoptman, M.J.; Hyde, J.S.; Kiviniemi, V.J.; Kotter, R.; Li, S.J.; Lin, C.P.; Lowe, M.J.; Mackay, C.; Madden, D.J.; Madsen, K.H.; Margulies, D.S.; Mayberg, H.S.; McMahon, K.; Monk, C.S.; Mostofsky, S.H.; Nagel, B.J.; Pekar, J.J.; Peltier, S.J.; Petersen, S.E.; Riedl, V.; Rombouts, S.A.R.B.; Rypma, B.; Schlaggar, B.L.; Schmidt, S.; Seidler, R.D.; Siegle, G.J.; Sorg, C.; Teng, G.J.; Veijola, J.; Villringer, A.; Walter, M.; Wang, L.; Weng, X.C.; Whitfield-Gabrieli, S.; Williamson, P.; Windischberger, C.; Zang, Y.F.; Zhang, H.Y.; Castellanos, F.X.; Milham, M.P.

    2010-01-01

    Although it is being successfully implemented for exploration of the genome, discovery science has eluded the functional neuroimaging community. The core challenge remains the development of common paradigms for interrogating the myriad functional systems in the brain without the constraints of a

  14. Weight lifting in the human brain

    NARCIS (Netherlands)

    Lange, F.P. de

    2006-01-01

    The world, just like us, is constantly changing. Making predictions about what will happen to you when you do something (and correcting these predictions based on what is actually happening) is therefore of vital importance. An influential theory states that the brain solves this challenge by using

  15. TV, Brain Waves and Human Behavior

    Science.gov (United States)

    Science News, 1978

    1978-01-01

    Describes the procedure to test the hypothesis that subjects' brain waves in response to a television flicker (distraction) would be smaller in amplitude during television programs of high, in contrast to low, interest. Results from 12 viewers support the hypothesis. (CP)

  16. Glycoblotting method allows for rapid and efficient glycome profiling of human Alzheimer's disease brain, serum and cerebrospinal fluid towards potential biomarker discovery.

    Science.gov (United States)

    Gizaw, Solomon T; Ohashi, Tetsu; Tanaka, Masakazu; Hinou, Hiroshi; Nishimura, Shin-Ichiro

    2016-08-01

    Understanding of the significance of posttranslational glycosylation in Alzheimer's disease (AD) is of growing importance for the investigation of the pathogenesis of AD as well as discovery research of the disease-specific serum biomarkers. We designed a standard protocol for the glycoblotting combined with MALDI-TOFMS to perform rapid and quantitative profiling of the glycan parts of glycoproteins (N-glycans) and glycosphingolipids (GSLs) using human AD's post-mortem samples such as brain tissues (dissected cerebral cortices such as frontal, parietal, occipital, and temporal domains), serum and cerebrospinal fluid (CSF). The structural profiles of the major N-glycans released from glycoproteins and the total expression levels of the glycans were found to be mostly similar between the brain tissues of the AD patients and those of the normal control group. In contrast, the expression levels of the serum and CSF protein N-glycans such as bisect-type and multiply branched glycoforms were increased significantly in AD patient group. In addition, the levels of some gangliosides such as GM1, GM2 and GM3 appeared to alter in the AD patient brain and serum samples when compared with the normal control groups. Alteration of the expression levels of major N- and GSL-glycans in human brain tissues, serum and CSF of AD patients can be monitored quantitatively by means of the glycoblotting-based standard protocols. The changes in the expression levels of the glycans derived from the human post-mortem samples uncovered by the standardized glycoblotting method provides potential serum biomarkers in central nervous system disorders and can contribute to the insight into the molecular mechanisms in the pathogenesis of neurodegenerative diseases and future drug discovery. Most importantly, the present preliminary trials using human post-mortem samples of AD patients suggest that large-scale serum glycomics cohort by means of various-types of human AD patients as well as the normal

  17. Severe malaria - a case of fatal Plasmodium knowlesi infection with post-mortem findings: a case report

    Directory of Open Access Journals (Sweden)

    Adem Patricia

    2010-01-01

    Full Text Available Abstract Background Zoonotic malaria caused by Plasmodium knowlesi is an important, but newly recognized, human pathogen. For the first time, post-mortem findings from a fatal case of knowlesi malaria are reported here. Case presentation A formerly healthy 40 year-old male became symptomatic 10 days after spending time in the jungle of North Borneo. Four days later, he presented to hospital in a state of collapse and died within two hours. He was hyponatraemic and had elevated blood urea, potassium, lactate dehydrogenase and amino transferase values; he was also thrombocytopenic and eosinophilic. Dengue haemorrhagic shock was suspected and a post-mortem examination performed. Investigations for dengue virus were negative. Blood for malaria parasites indicated hyperparasitaemia and single species P. knowlesi infection was confirmed by nested-PCR. Macroscopic pathology of the brain and endocardium showed multiple petechial haemorrhages, the liver and spleen were enlarged and lungs had features consistent with ARDS. Microscopic pathology showed sequestration of pigmented parasitized red blood cells in the vessels of the cerebrum, cerebellum, heart and kidney without evidence of chronic inflammatory reaction in the brain or any other organ examined. Brain sections were negative for intracellular adhesion molecule-1. The spleen and liver had abundant pigment containing macrophages and parasitized red blood cells. The kidney had evidence of acute tubular necrosis and endothelial cells in heart sections were prominent. Conclusions The overall picture in this case was one of systemic malaria infection that fit the WHO classification for severe malaria. Post-mortem findings in this case were unexpectedly similar to those that define fatal falciparum malaria, including cerebral pathology. There were important differences including the absence of coma despite petechial haemorrhages and parasite sequestration in the brain. These results suggest that further

  18. BrainNet Viewer: a network visualization tool for human brain connectomics.

    Science.gov (United States)

    Xia, Mingrui; Wang, Jinhui; He, Yong

    2013-01-01

    The human brain is a complex system whose topological organization can be represented using connectomics. Recent studies have shown that human connectomes can be constructed using various neuroimaging technologies and further characterized using sophisticated analytic strategies, such as graph theory. These methods reveal the intriguing topological architectures of human brain networks in healthy populations and explore the changes throughout normal development and aging and under various pathological conditions. However, given the huge complexity of this methodology, toolboxes for graph-based network visualization are still lacking. Here, using MATLAB with a graphical user interface (GUI), we developed a graph-theoretical network visualization toolbox, called BrainNet Viewer, to illustrate human connectomes as ball-and-stick models. Within this toolbox, several combinations of defined files with connectome information can be loaded to display different combinations of brain surface, nodes and edges. In addition, display properties, such as the color and size of network elements or the layout of the figure, can be adjusted within a comprehensive but easy-to-use settings panel. Moreover, BrainNet Viewer draws the brain surface, nodes and edges in sequence and displays brain networks in multiple views, as required by the user. The figure can be manipulated with certain interaction functions to display more detailed information. Furthermore, the figures can be exported as commonly used image file formats or demonstration video for further use. BrainNet Viewer helps researchers to visualize brain networks in an easy, flexible and quick manner, and this software is freely available on the NITRC website (www.nitrc.org/projects/bnv/).

  19. BrainNet Viewer: a network visualization tool for human brain connectomics.

    Directory of Open Access Journals (Sweden)

    Mingrui Xia

    Full Text Available The human brain is a complex system whose topological organization can be represented using connectomics. Recent studies have shown that human connectomes can be constructed using various neuroimaging technologies and further characterized using sophisticated analytic strategies, such as graph theory. These methods reveal the intriguing topological architectures of human brain networks in healthy populations and explore the changes throughout normal development and aging and under various pathological conditions. However, given the huge complexity of this methodology, toolboxes for graph-based network visualization are still lacking. Here, using MATLAB with a graphical user interface (GUI, we developed a graph-theoretical network visualization toolbox, called BrainNet Viewer, to illustrate human connectomes as ball-and-stick models. Within this toolbox, several combinations of defined files with connectome information can be loaded to display different combinations of brain surface, nodes and edges. In addition, display properties, such as the color and size of network elements or the layout of the figure, can be adjusted within a comprehensive but easy-to-use settings panel. Moreover, BrainNet Viewer draws the brain surface, nodes and edges in sequence and displays brain networks in multiple views, as required by the user. The figure can be manipulated with certain interaction functions to display more detailed information. Furthermore, the figures can be exported as commonly used image file formats or demonstration video for further use. BrainNet Viewer helps researchers to visualize brain networks in an easy, flexible and quick manner, and this software is freely available on the NITRC website (www.nitrc.org/projects/bnv/.

  20. Conservation of regional gene expression in mouse and human brain.

    Directory of Open Access Journals (Sweden)

    Andrew D Strand

    2007-04-01

    Full Text Available Many neurodegenerative diseases have a hallmark regional and cellular pathology. Gene expression analysis of healthy tissues may provide clues to the differences that distinguish resistant and sensitive tissues and cell types. Comparative analysis of gene expression in healthy mouse and human brain provides a framework to explore the ability of mice to model diseases of the human brain. It may also aid in understanding brain evolution and the basis for higher order cognitive abilities. Here we compare gene expression profiles of human motor cortex, caudate nucleus, and cerebellum to one another and identify genes that are more highly expressed in one region relative to another. We separately perform identical analysis on corresponding brain regions from mice. Within each species, we find that the different brain regions have distinctly different expression profiles. Contrasting between the two species shows that regionally enriched genes in one species are generally regionally enriched genes in the other species. Thus, even when considering thousands of genes, the expression ratios in two regions from one species are significantly correlated with expression ratios in the other species. Finally, genes whose expression is higher in one area of the brain relative to the other areas, in other words genes with patterned expression, tend to have greater conservation of nucleotide sequence than more widely expressed genes. Together these observations suggest that region-specific genes have been conserved in the mammalian brain at both the sequence and gene expression levels. Given the general similarity between patterns of gene expression in healthy human and mouse brains, we believe it is reasonable to expect a high degree of concordance between microarray phenotypes of human neurodegenerative diseases and their mouse models. Finally, these data on very divergent species provide context for studies in more closely related species that address

  1. Shortcomings of the Human Brain and Remedial Action by Religion

    Science.gov (United States)

    Reich, K. Helmut

    2010-01-01

    There is no consensus as to whether, and if so, in which regard and to what extent science and religion is needed for human survival. Here a circumscribed domain is taken up: the sovereignty and sufficiency of the human brain in this context. Several of its shortcomings are pointed out. Religion and other aspects of culture are needed for remedial…

  2. Anandamide hydrolysis by human cells in culture and brain

    NARCIS (Netherlands)

    Vliegenthart, J.F.G.; Maccarrone, M.; Stelt, M. van der; Rossi, A.; Veldink, G.A.; Finazzi Agrò, A.

    1998-01-01

    Anandamide (arachidonylethanolamide; AnNH) has important neuromodulatory and immunomodulatory activities. This lipid is rapidly taken up and hydrolyzed to arachidonate and ethanolamine in many organisms. As yet, AnNH inactivation has not been studied in humans. Here, a human brain fatty-acid amide

  3. The Evolution of Human Intelligence and the Coefficient of Additive Genetic Variance in Human Brain Size

    Science.gov (United States)

    Miller, Geoffrey F.; Penke, Lars

    2007-01-01

    Most theories of human mental evolution assume that selection favored higher intelligence and larger brains, which should have reduced genetic variance in both. However, adult human intelligence remains highly heritable, and is genetically correlated with brain size. This conflict might be resolved by estimating the coefficient of additive genetic…

  4. Expression of iron-related genes in human brain and brain tumors

    Directory of Open Access Journals (Sweden)

    Britton Robert S

    2009-04-01

    Full Text Available Abstract Background Defective iron homeostasis may be involved in the development of some diseases within the central nervous system. Although the expression of genes involved in normal iron balance has been intensively studied in other tissues, little is known about their expression in the brain. We investigated the mRNA levels of hepcidin (HAMP, HFE, neogenin (NEO1, transferrin receptor 1 (TFRC, transferrin receptor 2 (TFR2, and hemojuvelin (HFE2 in normal human brain, brain tumors, and astrocytoma cell lines. The specimens included 5 normal brain tissue samples, 4 meningiomas, one medulloblastoma, 3 oligodendrocytic gliomas, 2 oligoastrocytic gliomas, 8 astrocytic gliomas, and 3 astrocytoma cell lines. Results Except for hemojuvelin, all genes studied had detectable levels of mRNA. In most tumor types, the pattern of gene expression was diverse. Notable findings include high expression of transferrin receptor 1 in the hippocampus and medulla oblongata compared to other brain regions, low expression of HFE in normal brain with elevated HFE expression in meningiomas, and absence of hepcidin mRNA in astrocytoma cell lines despite expression in normal brain and tumor specimens. Conclusion These results indicate that several iron-related genes are expressed in normal brain, and that their expression may be dysregulated in brain tumors.

  5. BrainNet Europe's Code of Conduct for brain banking.

    Science.gov (United States)

    Klioueva, Natasja M; Rademaker, Marleen C; Dexter, David T; Al-Sarraj, Safa; Seilhean, Danielle; Streichenberger, Nathalie; Schmitz, Peer; Bell, Jeanne E; Ironside, James W; Arzberger, Thomas; Huitinga, Inge

    2015-07-01

    Research utilizing human tissue and its removal at post-mortem has given rise to many controversies in the media and posed many dilemmas in the fields of law and ethics. The law often lacks clear instructions and unambiguous guidelines. The absence of a harmonized international legislation with regard to post-mortem medical procedures and donation of tissue and organs contributes to the complexity of the issue. Therefore, within the BrainNet Europe (BNE) consortium, a consortium of 19 European brain banks, we drafted an ethical Code of Conduct for brain banking that covers basic legal rules and bioethical principles involved in brain banking. Sources include laws, regulations and guidelines (Declarations, Conventions, Recommendations, Guidelines and Directives) issued by international key organizations, such as the Council of Europe, European Commission, World Medical Association and World Health Organization. The Code of Conduct addresses fundamental topics as the rights of the persons donating their tissue, the obligations of the brain bank with regard to respect and observance of such rights, informed consent, confidentiality, protection of personal data, collections of human biological material and their management, and transparency and accountability within the organization of a brain bank. The Code of Conduct for brain banking is being adopted by the BNE network prior to being enshrined in official legislation for brain banking in Europe and beyond.

  6. The bilingual brain: Flexibility and control in the human cortex

    Science.gov (United States)

    Buchweitz, Augusto; Prat, Chantel

    2013-12-01

    The goal of the present review is to discuss recent cognitive neuroscientific findings concerning bilingualism. Three interrelated questions about the bilingual brain are addressed: How are multiple languages represented in the brain? how are languages controlled in the brain? and what are the real-world implications of experience with multiple languages? The review is based on neuroimaging research findings about the nature of bilingual processing, namely, how the brain adapts to accommodate multiple languages in the bilingual brain and to control which language should be used, and when. We also address how this adaptation results in differences observed in the general cognition of bilingual individuals. General implications for models of human learning, plasticity, and cognitive control are discussed.

  7. Electrical Guidance of Human Stem Cells in the Rat Brain

    Directory of Open Access Journals (Sweden)

    Jun-Feng Feng

    2017-07-01

    Full Text Available Limited migration of neural stem cells in adult brain is a roadblock for the use of stem cell therapies to treat brain diseases and injuries. Here, we report a strategy that mobilizes and guides migration of stem cells in the brain in vivo. We developed a safe stimulation paradigm to deliver directional currents in the brain. Tracking cells expressing GFP demonstrated electrical mobilization and guidance of migration of human neural stem cells, even against co-existing intrinsic cues in the rostral migration stream. Transplanted cells were observed at 3 weeks and 4 months after stimulation in areas guided by the stimulation currents, and with indications of differentiation. Electrical stimulation thus may provide a potential approach to facilitate brain stem cell therapies.

  8. The maternal brain and its plasticity in humans

    Science.gov (United States)

    Kim, Pilyoung; Strathearn, Lane; Swain, James E.

    2015-01-01

    Early mother-infant relationships play important roles in infants’ optimal development. New mothers undergo neurobiological changes that support developing mother-infant relationships regardless of great individual differences in those relationships. In this article, we review the neural plasticity in human mothers’ brains based on functional magnetic resonance imaging (fMRI) studies. First, we review the neural circuits that are involved in establishing and maintaining mother-infant relationships. Second, we discuss early postpartum factors (e.g., birth and feeding methods, hormones, and parental sensitivity) that are associated with individual differences in maternal brain neuroplasticity. Third, we discuss abnormal changes in the maternal brain related to psychopathology (i.e., postpartum depression, posttraumatic stress disorder, substance abuse) and potential brain remodeling associated with interventions. Last, we highlight potentially important future research directions to better understand normative changes in the maternal brain and risks for abnormal changes that may disrupt early mother-infant relationships. PMID:26268151

  9. Brain and Social Networks: Fundamental Building Blocks of Human Experience.

    Science.gov (United States)

    Falk, Emily B; Bassett, Danielle S

    2017-09-01

    How do brains shape social networks, and how do social ties shape the brain? Social networks are complex webs by which ideas spread among people. Brains comprise webs by which information is processed and transmitted among neural units. While brain activity and structure offer biological mechanisms for human behaviors, social networks offer external inducers or modulators of those behaviors. Together, these two axes represent fundamental contributors to human experience. Integrating foundational knowledge from social and developmental psychology and sociology on how individuals function within dyads, groups, and societies with recent advances in network neuroscience can offer new insights into both domains. Here, we use the example of how ideas and behaviors spread to illustrate the potential of multilayer network models. Copyright © 2017 Elsevier Ltd. All rights reserved.

  10. A family of hyperelastic models for human brain tissue

    Science.gov (United States)

    Mihai, L. Angela; Budday, Silvia; Holzapfel, Gerhard A.; Kuhl, Ellen; Goriely, Alain

    2017-09-01

    Experiments on brain samples under multiaxial loading have shown that human brain tissue is both extremely soft when compared to other biological tissues and characterized by a peculiar elastic response under combined shear and compression/tension: there is a significant increase in shear stress with increasing axial compression compared to a moderate increase with increasing axial tension. Recent studies have revealed that many widely used constitutive models for soft biological tissues fail to capture this characteristic response. Here, guided by experiments of human brain tissue, we develop a family of modeling approaches that capture the elasticity of brain tissue under varying simple shear superposed on varying axial stretch by exploiting key observations about the behavior of the nonlinear shear modulus, which can be obtained directly from the experimental data.

  11. Decade of the Brain 1990--2000: Maximizing human potential

    Energy Technology Data Exchange (ETDEWEB)

    1991-04-01

    The US Decade of the Brain offers scientists throughout the Federal Government a unique opportunity to advance and apply scientific knowledge about the brain and nervous system. During the next 10 years, scientists hope to maximize human potential through studies of human behavior, senses and communication, learning and memory, genetic/chemical alterations, and environmental interactions. Progress in these areas should lead to reductions in mortality from brain and nervous system disorders and to improvements in the quality of life. This report identifies nine research areas that could form the basis of an integrated program in the brain and behavioral sciences. A chart summarizing the Federal activities in these nine areas may be found at the back of the report. In addition, three areas that span the nine research areas -- basic research, technology and international activities -- are considered.

  12. Fundamental Dynamical Modes Underlying Human Brain Synchronization

    Directory of Open Access Journals (Sweden)

    Catalina Alvarado-Rojas

    2012-01-01

    Full Text Available Little is known about the long-term dynamics of widely interacting cortical and subcortical networks during the wake-sleep cycle. Using large-scale intracranial recordings of epileptic patients during seizure-free periods, we investigated local- and long-range synchronization between multiple brain regions over several days. For such high-dimensional data, summary information is required for understanding and modelling the underlying dynamics. Here, we suggest that a compact yet useful representation is given by a state space based on the first principal components. Using this representation, we report, with a remarkable similarity across the patients with different locations of electrode placement, that the seemingly complex patterns of brain synchrony during the wake-sleep cycle can be represented by a small number of characteristic dynamic modes. In this space, transitions between behavioral states occur through specific trajectories from one mode to another. These findings suggest that, at a coarse level of temporal resolution, the different brain states are correlated with several dominant synchrony patterns which are successively activated across wake-sleep states.

  13. Small-world human brain networks: Perspectives and challenges.

    Science.gov (United States)

    Liao, Xuhong; Vasilakos, Athanasios V; He, Yong

    2017-06-01

    Modelling the human brain as a complex network has provided a powerful mathematical framework to characterize the structural and functional architectures of the brain. In the past decade, the combination of non-invasive neuroimaging techniques and graph theoretical approaches enable us to map human structural and functional connectivity patterns (i.e., connectome) at the macroscopic level. One of the most influential findings is that human brain networks exhibit prominent small-world organization. Such a network architecture in the human brain facilitates efficient information segregation and integration at low wiring and energy costs, which presumably results from natural selection under the pressure of a cost-efficiency balance. Moreover, the small-world organization undergoes continuous changes during normal development and ageing and exhibits dramatic alterations in neurological and psychiatric disorders. In this review, we survey recent advances regarding the small-world architecture in human brain networks and highlight the potential implications and applications in multidisciplinary fields, including cognitive neuroscience, medicine and engineering. Finally, we highlight several challenging issues and areas for future research in this rapidly growing field. Copyright © 2017 Elsevier Ltd. All rights reserved.

  14. Normal cranial postmortem CT findings in children

    NARCIS (Netherlands)

    Sieswerda-Hoogendoorn, T.; Beenen, L. F. M.; van Rijn, R. R.

    2015-01-01

    Postmortem imaging (both CT and MRI) has become a widely used tool the last few years, both for adults and children. If it would be known which findings are normal postmortem changes, interpretation of abnormal findings becomes less ambiguous. Our aim was to describe postmortem intracranial

  15. Three-dimensional microtomographic imaging of human brain cortex

    CERN Document Server

    Mizutania, Ryuta; Uesugi, Kentaro; Ohyama, Masami; Takekoshi, Susumu; Osamura, R Yoshiyuki; Suzuki, Yoshio

    2016-01-01

    This paper describes an x-ray microtomographic technique for imaging the three-dimensional structure of the human cerebral cortex. Neurons in the brain constitute a neural circuit as a three-dimensional network. The brain tissue is composed of light elements that give little contrast in a hard x-ray transmission image. The contrast was enhanced by staining neural cells with metal compounds. The obtained structure revealed the microarchitecture of the gray and white matter regions of the frontal cortex, which is responsible for the higher brain functions.

  16. Human-like brain hemispheric dominance in birdsong learning

    OpenAIRE

    Moorman, Sanne; Gobes, Sharon M. H.; Kuijpers, Maaike; Kerkhofs, Amber; Zandbergen, Matthijs A.; Bolhuis, Johan J.

    2012-01-01

    Unlike nonhuman primates, songbirds learn to vocalize very much like human infants acquire spoken language. In humans, Broca’s area in the frontal lobe and Wernicke’s area in the temporal lobe are crucially involved in speech production and perception, respectively. Songbirds have analogous brain regions that show a similar neural dissociation between vocal production and auditory perception and memory. In both humans and songbirds, there is evidence for lateralization of neural responsivenes...

  17. Distribution of vesicular glutamate transporters in the human brain

    Directory of Open Access Journals (Sweden)

    Erika eVigneault

    2015-03-01

    Full Text Available Glutamate is the major excitatory transmitter in the brain. Vesicular glutamate transporters (VGLUT1-3 are responsible for uploading glutamate into synaptic vesicles. VGLUT1 and VGLUT2 are considered as specific markers of canonical glutamatergic neurons, while VGLUT3 is found in neurons previously shown to use other neurotransmitters than glutamate. Although there exists a rich literature on the localization of these glutamatergic markers in the rodent brain, little is currently known about the distribution of VGLUT1-3 in the human brain. In the present study, using subtype specific probes and antisera, we examined the localization of the three vesicular glutamate transporters in the human brain by in situ hybridization, immunoautoradiography and immunohistochemistry. We found that the VGLUT1 transcript was highly expressed in the cerebral cortex, hippocampus and cerebellum, whereas VGLUT2 mRNA was mainly found in the thalamus and brainstem. VGLUT3 mRNA was localized in scarce neurons within the cerebral cortex, hippocampus, striatum and raphe nuclei. Following immunoautoradiographic labeling, intense VGLUT1- and VGLUT2-immunoreactivities were observed in all regions investigated (cerebral cortex, hippocampus, caudate-putamen, cerebellum, thalamus, amygdala, substantia nigra, raphe while VGLUT3 was absent from the thalamus and cerebellum. This extensive mapping of VGLUT1-3 in human brain reveals distributions that correspond for the most part to those previously described in rodent brains.

  18. Several methods to determine heavy metals in the human brain

    Science.gov (United States)

    Andrási, Erzsébet; Igaz, Sarolta; Szoboszlai, Norbert; Farkas, Éva; Ajtony, Zsolt

    1999-05-01

    The determination of naturally occurring heavy metals in various parts of the human brain is discussed. The patients had no diseases in their central nervous systems (five individuals, mean age 70 years). Twenty brain parts were selected from both hemispheres. The analysis was carried out by graphite furnace atomic absorption spectrometry, inductively coupled plasma atomic emission spectrometry and instrumental neutron activation analysis methods. Accuracy and precision of the applied techniques were tested by using standard reference materials. Two digestion methods were used to dissolve the brain samples for ICP-AES and GF-AAS. One was performed in a Parr-bomb and the second in a microwave oven. The present results show a non-homogeneous distribution of the essential elements (Cu, Fe, Mn, Zn) in normal human brain. Corresponding regions in both hemispheres showed an almost identical concentration of these elements. In the case of toxic elements (Pb, Cd) an average value in different brain regions can not be established because of the high variability of individual data. This study indicates that beside differences in Pb and Cd intake with foods or cigarette smoke inhalation, the main factors of the high inter-individual variability of these element concentrations in human brain parts may be a marked difference in individual elimination or accumulation capabilities.

  19. A psychology of the human brain-gut-microbiome axis.

    Science.gov (United States)

    Allen, Andrew P; Dinan, Timothy G; Clarke, Gerard; Cryan, John F

    2017-04-01

    In recent years, we have seen increasing research within neuroscience and biopsychology on the interactions between the brain, the gastrointestinal tract, the bacteria within the gastrointestinal tract, and the bidirectional relationship between these systems: the brain-gut-microbiome axis. Although research has demonstrated that the gut microbiota can impact upon cognition and a variety of stress-related behaviours, including those relevant to anxiety and depression, we still do not know how this occurs. A deeper understanding of how psychological development as well as social and cultural factors impact upon the brain-gut-microbiome axis will contextualise the role of the axis in humans and inform psychological interventions that improve health within the brain-gut-microbiome axis. Interventions ostensibly aimed at ameliorating disorders in one part of the brain-gut-microbiome axis (e.g., psychotherapy for depression) may nonetheless impact upon other parts of the axis (e.g., microbiome composition and function), and functional gastrointestinal disorders such as irritable bowel syndrome represent a disorder of the axis, rather than an isolated problem either of psychology or of gastrointestinal function. The discipline of psychology needs to be cognisant of these interactions and can help to inform the future research agenda in this emerging field of research. In this review, we outline the role psychology has to play in understanding the brain-gut-microbiome axis, with a focus on human psychology and the use of research in laboratory animals to model human psychology.

  20. Prodynorphin CpG-SNPs associated with alcohol dependence: elevated methylation in the brain of human alcoholics.

    Science.gov (United States)

    Taqi, Malik Mumtaz; Bazov, Igor; Watanabe, Hiroyuki; Sheedy, Donna; Harper, Clive; Alkass, Kanar; Druid, Henrik; Wentzel, Parri; Nyberg, Fred; Yakovleva, Tatjana; Bakalkin, Georgy

    2011-07-01

    The genetic, epigenetic and environmental factors may influence the risk for neuropsychiatric disease through their effects on gene transcription. Mechanistically, these effects may be integrated through regulation of methylation of CpG dinucleotides overlapping with single-nucleotide polymorphisms (SNPs) associated with a disorder. We addressed this hypothesis by analyzing methylation of prodynorphin (PDYN) CpG-SNPs associated with alcohol dependence, in human alcoholics. Postmortem specimens of the dorsolateral prefrontal cortex (dl-PFC) involved in cognitive control of addictive behavior were obtained from 14 alcohol-dependent and 14 control subjects. Methylation was measured by pyrosequencing after bisulfite treatment of DNA. DNA binding proteins were analyzed by electromobility shift assay. Three PDYN CpG-SNPs associated with alcoholism were found to be differently methylated in the human brain. In the dl-PFC of alcoholics, methylation levels of the C, non-risk variant of 3'-untranslated region (3'-UTR) SNP (rs2235749; C > T) were increased, and positively correlated with dynorphins. A DNA-binding factor that differentially targeted the T, risk allele and methylated and unmethylated C allele of this SNP was identified in the brain. The findings suggest a causal link between alcoholism-associated PDYN 3'-UTR CpG-SNP methylation, activation of PDYN transcription and vulnerability of individuals with the C, non-risk allele(s) to develop alcohol dependence. © 2011 The Authors, Addiction Biology © 2011 Society for the Study of Addiction.

  1. Purification and characterization of a human brain galectin-1 ligand.

    Science.gov (United States)

    Chadli, A; LeCaer, J P; Bladier, D; Joubert-Caron, R; Caron, M

    1997-04-01

    Our previous studies have characterized an endogenous lectin from human brain identified as galectin-1. A soluble ligand of galectin-1 was purified from human brain by affinity chromatography and preparative electrophoresis. The purified ligand (termed HBGp82, for human brain galectin-1-binding polypeptide of 82,000 daltons) has an apparent molecular mass of 82 kDa and is glycosylated by N-linked biantennary complex structures. HBGp82 was partially characterized by microsequencing of peptide fragments. Similar peptides were found in a heat shock of protein of 90,000 daltons, hsp90. However, comparison of apparent molecular weights and matrix-assisted laser desorption mass spectrometry clearly showed that HBGp82 differs to some degree from hsp90.

  2. Phosphorylethanolamine content of human brain tumors.

    Science.gov (United States)

    Kinoshita, Y; Yokota, A; Koga, Y

    1994-12-01

    Phosphorylethanolamine (PEA) is the major component of the phosphomonoester peak detected by phosphorus-31 magnetic resonance spectroscopy, but the absolute concentration has not been determined. This study measured the PEA concentration in biopsy specimens of brain tumors and lobectomized cerebral cortex using high-performance liquid chromatography. The concentration of PEA was 118.5 +/- 10.0 mumol/100 g wet wt in cortex, and was significantly higher in malignant gliomas, metastatic pulmonary adenocarcinoma, and neurinoma. The concentration of PEA was especially high in pituitary adenoma, malignant lymphoma, and medulloblastoma.

  3. Human cadaver brain infusion skull model for neurosurgical training.

    Science.gov (United States)

    Olabe, Jon; Olabe, Javier; Roda, Jose Maria; Sancho, Vidal

    2011-01-01

    Microsurgical technique and anatomical knowledge require extensive laboratory training. Human cadaver models are especially valuable as they supply a good microsurgical training environment simultaneously providing authentic brain anatomy. We developed the "skull infusion model" as an extension of our previous "brain infusion model" taking it a step further maintaining simplicity but enhancing realism. Four human cadaveric brains donated for educational purposes were explanted at autopsy. The specimens were prepared cannulating carotid and vertebral arteries with plastic tubings, flushed with abundant water and fixed for 1 month in formaldehyde. They were then enclosed with white silk clothing (emulating the dura mater) and inserted into human skulls cut previously into two pieces. Tap water at a flow rate of 10 L/h was infused through the arterial tubings. Diverse microsurgical procedures were performed by two trainees, including craniotomies with microsurgical approaches and techniques such as sylvian fissure exposure, extra-intracranial and intra-intracranial bypass, approaches to the ventricles and choroidal fissure opening. The water infusion fills the arterial system, leaking into the interstitial and cisternal space and finally moistening the whole specimen. This makes vascular microsurgical techniques become extremely realistic, increasing its compliance making manipulations easier and more authentic. Standard microsurgical laboratories frequently have difficulties to work with decapitated human cadaver heads but could have human brains readily available. Using the infusion model and inserting it in a human skull makes the environment much more realistic. Its simplicity and inexpensiveness make it a good alternative for developing microsurgical techniques.

  4. Determination of clozapine, and five antidepressants in human plasma, serum and whole blood by gas chromatography-mass spectrometry: A simple tool for clinical and postmortem toxicological analysis.

    Science.gov (United States)

    Boumba, Vassiliki A; Rallis, George; Petrikis, Petros; Vougiouklakis, Theodore; Mavreas, Venetsanos

    2016-12-01

    In this study, we describe a simple and rapid method for the determination of the antipsychotic drug clozapine and five commonly co-administered antidepressants - bupropion, mirtazapine, sertraline, clomipramine and citalopram - in serum, plasma and whole blood. Sample preparation includes solid phase extraction of analytes and determination of drug concentrations by gas chromatography-mass spectrometry without any derivatization steps. The method was fully validated according to international criteria and can be successfully applied for routine analyses. Correlation coefficients of calibration curves for the tested drugs in the three specimens were in the range 0.9977-0.9999. Intra-day and inter-day precisions ranged from 0.81-7.85% and 3.60-12.91% respectively for the studied analytes and matrices. Recoveries were satisfactory for different concentrations of each drug in each specimen allowing accurate determinations in the range from sub-therapeutic to toxic levels. The presented method shows acceptable sensitivity, linearity in wide concentration ranges (sub-therapeutic, therapeutic, supra-therapeutic/toxic levels), it is simple and rapid and it is applicable for qualitative and quantitative routine toxicological analyses of clinical and postmortem cases. Copyright © 2016 Elsevier B.V. All rights reserved.

  5. Quantification of 16 QT-prolonging Drugs and Metabolites in Human Postmortem Blood and Cardiac Tissue Using UPLC–MS-MS

    DEFF Research Database (Denmark)

    Mikkelsen, Christian Reuss; Jornil, Jakob; Vukelic Andersen, Ljubica

    2016-01-01

    QT-prolonging compounds present a treatment risk in mentally ill patients. Knowledge of the concentration in the heart compared with blood is necessary to assess the cardiac toxicity of QT-prolonging compounds. To address this issue, this article presents a validated analytical method for the qua......QT-prolonging compounds present a treatment risk in mentally ill patients. Knowledge of the concentration in the heart compared with blood is necessary to assess the cardiac toxicity of QT-prolonging compounds. To address this issue, this article presents a validated analytical method....... Validation results showed that the bias was ±15% and precision was ≤15% for all compounds in both matrices. The recovery ranged from 78.8 to 127.4%, and the matrix effect ranged from 61.0 to 128.7% across both matrices. The limit of detection and the lower limit of quantification were below the therapeutic...... concentrations of the prescription drugs. No noteworthy degradation during storage of the extracts was detected. The method was applied in five authentic cases of mentally ill patients. In conclusion, an analytical method was successfully developed and validated for the quantification of QTD in postmortem whole...

  6. Quantification of 16 QT-prolonging Drugs and Metabolites in Human Postmortem Blood and Cardiac Tissue Using UPLC-MS-MS

    DEFF Research Database (Denmark)

    Mikkelsen, Christian R; Jornil, Jakob; Andersen, Ljubica V

    2016-01-01

    QT-prolonging compounds present a treatment risk in mentally ill patients. Knowledge of the concentration in the heart compared with blood is necessary to assess the cardiac toxicity of QT-prolonging compounds. To address this issue, this article presents a validated analytical method for the qua......QT-prolonging compounds present a treatment risk in mentally ill patients. Knowledge of the concentration in the heart compared with blood is necessary to assess the cardiac toxicity of QT-prolonging compounds. To address this issue, this article presents a validated analytical method....... Validation results showed that the bias was ±15% and precision was ≤15% for all compounds in both matrices. The recovery ranged from 78.8 to 127.4%, and the matrix effect ranged from 61.0 to 128.7% across both matrices. The limit of detection and the lower limit of quantification were below the therapeutic...... concentrations of the prescription drugs. No noteworthy degradation during storage of the extracts was detected. The method was applied in five authentic cases of mentally ill patients. In conclusion, an analytical method was successfully developed and validated for the quantification of QTD in postmortem whole...

  7. Human-like brain hemispheric dominance in birdsong learning.

    Science.gov (United States)

    Moorman, Sanne; Gobes, Sharon M H; Kuijpers, Maaike; Kerkhofs, Amber; Zandbergen, Matthijs A; Bolhuis, Johan J

    2012-07-31

    Unlike nonhuman primates, songbirds learn to vocalize very much like human infants acquire spoken language. In humans, Broca's area in the frontal lobe and Wernicke's area in the temporal lobe are crucially involved in speech production and perception, respectively. Songbirds have analogous brain regions that show a similar neural dissociation between vocal production and auditory perception and memory. In both humans and songbirds, there is evidence for lateralization of neural responsiveness in these brain regions. Human infants already show left-sided dominance in their brain activation when exposed to speech. Moreover, a memory-specific left-sided dominance in Wernicke's area for speech perception has been demonstrated in 2.5-mo-old babies. It is possible that auditory-vocal learning is associated with hemispheric dominance and that this association arose in songbirds and humans through convergent evolution. Therefore, we investigated whether there is similar song memory-related lateralization in the songbird brain. We exposed male zebra finches to tutor or unfamiliar song. We found left-sided dominance of neuronal activation in a Broca-like brain region (HVC, a letter-based name) of juvenile and adult zebra finch males, independent of the song stimulus presented. In addition, juvenile males showed left-sided dominance for tutor song but not for unfamiliar song in a Wernicke-like brain region (the caudomedial nidopallium). Thus, left-sided dominance in the caudomedial nidopallium was specific for the song-learning phase and was memory-related. These findings demonstrate a remarkable neural parallel between birdsong and human spoken language, and they have important consequences for our understanding of the evolution of auditory-vocal learning and its neural mechanisms.

  8. Measuring dopamine release in the human brain with PET

    Energy Technology Data Exchange (ETDEWEB)

    Volkow, N.D. [Brookhaven National Lab., Upton, NY (United States)]|[State Univ. of New York at Stony Brook, Stony Brook, NY (United States). Dept. of Psychiatry; Fowler, J.S.; Logan, J.; Wang, G.J. [Brookhaven National Lab., Upton, NY (United States)

    1995-12-01

    The dopamine system is involved in the regulation of brain regions that subserve motor, cognitive and motivational behaviors. Disruptions of dopamine (DA) function have ben implicated in neurological and psychiatric illnesses including substance abuse as well as on some of the deficits associated with aging of the human brain. This has made the DA system an important topic in research in the neurosciences and neuroimaging as well as an important molecular target for drug development. Positron Emission Tomography (PET), was the first technology that enabled direct measurement of components of the DA system in the living human brain. Imaging studies of DA in the living brain have been indirect, relying on the development of radiotracers to label DA receptors, DA transporters, compounds which have specificity for the enzymes which degrade synaptic DA. Additionally, through the use of tracers that provide information on regional brain activity (ie brain glucose metabolism and cerebral blood flow) and of appropriate pharmacological interventions, it has been possible to assess the functional consequences of changes in brain DA activity. DA specific ligands have been useful in the evaluation of patients with neuropsychiatric illnesses as well as to investigate receptor blockade by antipsychotic drugs. A limitation of strategies that rely on the use of DA specific ligands is that the measures do not necessarily reflect the functional state of the dopaminergic system and that there use to study the effects of drugs is limited to the investigation of receptor or transporter occupancy. Newer strategies have been developed in an attempt to provide with information on dopamine release and on the functional responsivity of the DA system in the human brain. This in turn allows to investigate the effects of pharmacological agent in an analogous way to what is done with microdialysis techniques.

  9. Fetal microchimerism in human brain tumors.

    Science.gov (United States)

    Broestl, Lauren; Rubin, Joshua B; Dahiya, Sonika

    2017-09-18

    Sex differences in cancer incidence and survival, including central nervous system tumors, are well documented. Multiple mechanisms contribute to sex differences in health and disease. Recently, the presence of fetal-in-maternal microchimeric cells has been shown to have prognostic significance in breast and colorectal cancers. The frequency and potential role of these cells has not been investigated in brain tumors. We therefore selected two common primary adult brain tumors for this purpose: meningioma, which is sex hormone responsive and has a higher incidence in women, and glioblastoma, which is sex hormone independent and occurs more commonly in men. Quantitative PCR was used to detect the presence of male DNA in tumor samples from women with a positive history of male pregnancy and a diagnosis of either glioblastoma or meningioma. Fluorescence in situ hybridization for the X and Y chromosomes was used to verify the existence of intact male cells within tumor tissue. Fetal microchimerism was found in approximately 80% of glioblastoma cases and 50% of meningioma cases. No correlations were identified between the presence of microchimerism and commonly used clinical or molecular diagnostic features of disease. The impact of fetal microchimeric cells should be evaluated prospectively. © 2017 International Society of Neuropathology.

  10. Radial and tangential neuronal migration pathways in the human fetal brain: anatomically distinct patterns of diffusion MRI coherence

    Science.gov (United States)

    Kolasinski, James; Takahashi, Emi; Stevens, Allison A.; Benner, Thomas; Fischl, Bruce; Zöllei, Lilla; Grant, P. Ellen

    2014-01-01

    Corticogenesis is underpinned by a complex process of subcortical neuroproliferation, followed by highly orchestrated cellular migration. A greater appreciation of the processes involved in human fetal corticogenesis is vital to gaining an understanding of how developmental disturbances originating in gestation could establish a variety of complex neuropathology manifesting in childhood, or even in adult life. Magnetic resonance imaging modalities offer a unique insight into anatomical structure, and increasingly infer information regarding underlying microstructure in the human brain. In this study we applied a combination of high-resolution structural and diffusion-weighted magnetic resonance imaging to a unique cohort of three post-mortem fetal brain specimens, aged between 19 and 22 post-conceptual weeks. Specifically, we sought to assess patterns of diffusion coherence associated with subcortical neuroproliferative structures: the pallial ventricular/subventricular zone and subpallial ganglionic eminence. Two distinct three-dimensional patterns of diffusion coherence were evident: a clear radial pattern originating in ventricular/subventricular zone, and a tangentio-radial patterns originating in ganglionic eminence. These patterns appeared to regress in a caudo-rostral and lateral-ventral to medial-dorsal direction across the short period of fetal development under study. Our findings demonstrate for the first time distinct patterns of diffusion coherence associated with known anatomical proliferative structures. The radial pattern associated with dorsopallial ventricular/subventricular zone and the tangentio-radial pattern associated with subpallial ganglionic eminence are consistent with reports of radial-glial mediated neuronal migration pathways identified during human corticogenesis, supported by our prior studies of comparative fetal diffusion MRI and histology. The ability to assess such pathways in the fetal brain using MR imaging offers a unique

  11. Short parietal lobe connections of the human and monkey brain

    DEFF Research Database (Denmark)

    Catani, Marco; Robertsson, Naianna; Beyh, Ahmad

    2017-01-01

    The parietal lobe has a unique place in the human brain. Anatomically, it is at the crossroad between the frontal, occipital, and temporal lobes, thus providing a middle ground for multimodal sensory integration. Functionally, it supports higher cognitive functions that are characteristic...... in the medial and lateral aspects of the parietal lobe were identified in both species. A tract connecting the medial parietal cortex to the lateral inferior parietal cortex was observed in the monkey brain only. Our findings suggest a consistent pattern of intralobar parietal connections between humans...

  12. PET evaluation of the dopamine system of the human brain

    Energy Technology Data Exchange (ETDEWEB)

    Volkow, N.D.; Fowler, J.S.; Gatley, S. [Brookhaven National Laboratory, Upton, NY (United States)]|[SUNY-Stony Brook, NY (United States)] [and others

    1996-07-01

    Dopamine plays a pivotal role in the regulation and control of movement, motivation and cognition. It also is closely linked to reward, reinforcement and addiction. Abnormalities in brain dopamine are associated with many neurological and psychiatric disorders including Parkinson`s disease, schizophrenia and substance abuse. This close association between dopamine and neurological and psychiatric diseases and with substance abuse make it an important topic in research in the neurosciences and an important molecular target in drug development. PET enables the direct measurement of components of the dopamine system in the living human brain. It relies on radiotracers which label dopamine receptors, dopamine transporters, precursors of dopamine or compounds which have specificity for the enzymes which degrade dopamine. Additionally, by using tracers that provide information on regional brain metabolism or blood flow as well as neurochemically specific pharmacological interventions, PET can be used to assess the functional consequences of change in brain dopamine activity. PET dopamine measurements have been used to investigate the normal human brain and its involvement in psychiatric and neurological diseases. It has also been used in psychopharmacological research to investigate dopamine drugs used in the treatment of Parkinson`s disease and of schizophrenia as well as to investigate the effects of drugs of abuse on the dopamine system. Since various functional and neurochemical parameters can be studied in the same subject, PET enables investigation of the functional integrity of the dopamine system in the human brain and investigation of the interactions of dopamine with other neurotransmitters. This paper summarizes the different tracers and experimental strategies developed to evaluate the various elements of the dopamine system in the human brain with PET and their applications to clinical research. 254 refs., 7 figs., 3 tabs.

  13. Gender development and the human brain.

    Science.gov (United States)

    Hines, Melissa

    2011-01-01

    Convincing evidence indicates that prenatal exposure to the gonadal hormone, testosterone, influences the development of children's sex-typical toy and activity interests. In addition, growing evidence shows that testosterone exposure contributes similarly to the development of other human behaviors that show sex differences, including sexual orientation, core gender identity, and some, though not all, sex-related cognitive and personality characteristics. In addition to these prenatal hormonal influences, early infancy and puberty may provide additional critical periods when hormones influence human neurobehavioral organization. Sex-linked genes could also contribute to human gender development, and most sex-related characteristics are influenced by socialization and other aspects of postnatal experience, as well. Neural mechanisms underlying the influences of gonadal hormones on human behavior are beginning to be identified. Although the neural mechanisms underlying experiential influences remain largely uninvestigated, they could involve the same neural circuitry as that affected by hormones.

  14. Characterization of genetic miscoding lesions caused by postmortem damage

    DEFF Research Database (Denmark)

    Gilbert, M Thomas P; Hansen, Anders J; Willerslev, Eske

    2002-01-01

    The spectrum of postmortem damage in mitochondrial DNA was analyzed in a large data set of cloned sequences from ancient human specimens. The most common forms of damage observed are two complementary groups of transitions, termed "type 1" (adenine-->guanine/thymine-->cytosine) and "type 2" (cyto...

  15. Comprehensive cellular‐resolution atlas of the adult human brain

    Science.gov (United States)

    Royall, Joshua J.; Sunkin, Susan M.; Ng, Lydia; Facer, Benjamin A.C.; Lesnar, Phil; Guillozet‐Bongaarts, Angie; McMurray, Bergen; Szafer, Aaron; Dolbeare, Tim A.; Stevens, Allison; Tirrell, Lee; Benner, Thomas; Caldejon, Shiella; Dalley, Rachel A.; Dee, Nick; Lau, Christopher; Nyhus, Julie; Reding, Melissa; Riley, Zackery L.; Sandman, David; Shen, Elaine; van der Kouwe, Andre; Varjabedian, Ani; Write, Michelle; Zollei, Lilla; Dang, Chinh; Knowles, James A.; Koch, Christof; Phillips, John W.; Sestan, Nenad; Wohnoutka, Paul; Zielke, H. Ronald; Hohmann, John G.; Jones, Allan R.; Bernard, Amy; Hawrylycz, Michael J.; Hof, Patrick R.; Fischl, Bruce

    2016-01-01

    ABSTRACT Detailed anatomical understanding of the human brain is essential for unraveling its functional architecture, yet current reference atlases have major limitations such as lack of whole‐brain coverage, relatively low image resolution, and sparse structural annotation. We present the first digital human brain atlas to incorporate neuroimaging, high‐resolution histology, and chemoarchitecture across a complete adult female brain, consisting of magnetic resonance imaging (MRI), diffusion‐weighted imaging (DWI), and 1,356 large‐format cellular resolution (1 µm/pixel) Nissl and immunohistochemistry anatomical plates. The atlas is comprehensively annotated for 862 structures, including 117 white matter tracts and several novel cyto‐ and chemoarchitecturally defined structures, and these annotations were transferred onto the matching MRI dataset. Neocortical delineations were done for sulci, gyri, and modified Brodmann areas to link macroscopic anatomical and microscopic cytoarchitectural parcellations. Correlated neuroimaging and histological structural delineation allowed fine feature identification in MRI data and subsequent structural identification in MRI data from other brains. This interactive online digital atlas is integrated with existing Allen Institute for Brain Science gene expression atlases and is publicly accessible as a resource for the neuroscience community. J. Comp. Neurol. 524:3127–3481, 2016. © 2016 The Authors The Journal of Comparative Neurology Published by Wiley Periodicals, Inc. PMID:27418273

  16. Human brain functional MRI and DTI visualization with virtual reality.

    Science.gov (United States)

    Chen, Bin; Moreland, John; Zhang, Jingyu

    2011-12-01

    Magnetic resonance diffusion tensor imaging (DTI) and functional MRI (fMRI) are two active research areas in neuroimaging. DTI is sensitive to the anisotropic diffusion of water exerted by its macromolecular environment and has been shown useful in characterizing structures of ordered tissues such as the brain white matter, myocardium, and cartilage. The diffusion tensor provides two new types of information of water diffusion: the magnitude and the spatial orientation of water diffusivity inside the tissue. This information has been used for white matter fiber tracking to review physical neuronal pathways inside the brain. Functional MRI measures brain activations using the hemodynamic response. The statistically derived activation map corresponds to human brain functional activities caused by neuronal activities. The combination of these two methods provides a new way to understand human brain from the anatomical neuronal fiber connectivity to functional activities between different brain regions. In this study, virtual reality (VR) based MR DTI and fMRI visualization with high resolution anatomical image segmentation and registration, ROI definition and neuronal white matter fiber tractography visualization and fMRI activation map integration is proposed. Rationale and methods for producing and distributing stereoscopic videos are also discussed.

  17. Neurospin Seminar: From the Proton to the Human Brain

    CERN Multimedia

    CERN. Geneva

    2016-01-01

    From the Proton to the Human Brain Speaker: Prof Denis Le Bihan Abstract: The understanding of the human brain is one of the main scientific challenges of the 21st century. In the early 2000s the French Atomic Energy Commission (CEA) launched a program to conceive and build a “human brain explorer”, the first human MRI scanner operating at 11.7T. This scanner was envisioned to be part of the ambitious Iseult project, bridging together industrial and academic partners to push the limits of molecular neuroimaging, from mouse to man, using Ultra-High Field (UHF) MRI. In this seminar a summary of the main features of this magnet, and the neuroscience and medical targets of NeuroSpin where this outstanding instrument will be installed in 2017 will be surveyed. The unprecedented resolution and the new contrasts allowed by such UHF magnets, in combination with innovative concepts in physics and neurobiology, will allow to explore the human brain at a mesoscale at which everything remains to d...

  18. Addiction circuitry in the human brain (*).

    Energy Technology Data Exchange (ETDEWEB)

    Volkow, N.D.; Wang, G.; Volkow, N.D.; Wang, G.-J.; Fowler, J.S.; Tomasi, D.

    2011-09-27

    A major challenge in understanding substance-use disorders lies in uncovering why some individuals become addicted when exposed to drugs, whereas others do not. Although genetic, developmental, and environmental factors are recognized as major contributors to a person's risk of becoming addicted, the neurobiological processes that underlie this vulnerability are still poorly understood. Imaging studies suggest that individual variations in key dopamine-modulated brain circuits, including circuits involved in reward, memory, executive function, and motivation, contribute to some of the differences in addiction vulnerability. A better understanding of the main circuits affected by chronic drug use and the influence of social stressors, developmental trajectories, and genetic background on these circuits is bound to lead to a better understanding of addiction and to more effective strategies for the prevention and treatment of substance-use disorders.

  19. The sleep-deprived human brain.

    Science.gov (United States)

    Krause, Adam J; Simon, Eti Ben; Mander, Bryce A; Greer, Stephanie M; Saletin, Jared M; Goldstein-Piekarski, Andrea N; Walker, Matthew P

    2017-07-01

    How does a lack of sleep affect our brains? In contrast to the benefits of sleep, frameworks exploring the impact of sleep loss are relatively lacking. Importantly, the effects of sleep deprivation (SD) do not simply reflect the absence of sleep and the benefits attributed to it; rather, they reflect the consequences of several additional factors, including extended wakefulness. With a focus on neuroimaging studies, we review the consequences of SD on attention and working memory, positive and negative emotion, and hippocampal learning. We explore how this evidence informs our mechanistic understanding of the known changes in cognition and emotion associated with SD, and the insights it provides regarding clinical conditions associated with sleep disruption.

  20. ``the Human BRAIN & Fractal quantum mechanics''

    Science.gov (United States)

    Rosary-Oyong, Se, Glory

    In mtDNA ever retrieved from Iman Tuassoly, et.al:Multifractal analysis of chaos game representation images of mtDNA''.Enhances the price & valuetales of HE. Prof. Dr-Ing. B.J. HABIBIE's N-219, in J. Bacteriology, Nov 1973 sought:'' 219 exist as separate plasmidDNA species in E.coli & Salmonella panama'' related to ``the brain 2 distinct molecular forms of the (Na,K)-ATPase..'' & ``neuron maintains different concentration of ions(charged atoms'' thorough Rabi & Heisenber Hamiltonian. Further, after ``fractal space time are geometric analogue of relativistic quantum mechanics''[Ord], sought L.Marek Crnjac: ``Chaotic fractals at the root of relativistic quantum physics''& from famous Nottale: ``Scale relativity & fractal space-time:''Application to Quantum Physics , Cosmology & Chaotic systems'',1995. Acknowledgements to HE. Mr. H. TUK SETYOHADI, Jl. Sriwijaya Raya 3, South-Jakarta, INDONESIA.

  1. Mathematical logic in the human brain: syntax.

    Directory of Open Access Journals (Sweden)

    Roland Friedrich

    Full Text Available Theory predicts a close structural relation of formal languages with natural languages. Both share the aspect of an underlying grammar which either generates (hierarchically structured expressions or allows us to decide whether a sentence is syntactically correct or not. The advantage of rule-based communication is commonly believed to be its efficiency and effectiveness. A particularly important class of formal languages are those underlying the mathematical syntax. Here we provide brain-imaging evidence that the syntactic processing of abstract mathematical formulae, written in a first order language, is, indeed efficient and effective as a rule-based generation and decision process. However, it is remarkable, that the neural network involved, consisting of intraparietal and prefrontal regions, only involves Broca's area in a surprisingly selective way. This seems to imply that despite structural analogies of common and current formal languages, at the neural level, mathematics and natural language are processed differently, in principal.

  2. The modular and integrative functional architecture of the human brain.

    Science.gov (United States)

    Bertolero, Maxwell A; Yeo, B T Thomas; D'Esposito, Mark

    2015-12-08

    Network-based analyses of brain imaging data consistently reveal distinct modules and connector nodes with diverse global connectivity across the modules. How discrete the functions of modules are, how dependent the computational load of each module is to the other modules' processing, and what the precise role of connector nodes is for between-module communication remains underspecified. Here, we use a network model of the brain derived from resting-state functional MRI (rs-fMRI) data and investigate the modular functional architecture of the human brain by analyzing activity at different types of nodes in the network across 9,208 experiments of 77 cognitive tasks in the BrainMap database. Using an author-topic model of cognitive functions, we find a strong spatial correspondence between the cognitive functions and the network's modules, suggesting that each module performs a discrete cognitive function. Crucially, activity at local nodes within the modules does not increase in tasks that require more cognitive functions, demonstrating the autonomy of modules' functions. However, connector nodes do exhibit increased activity when more cognitive functions are engaged in a task. Moreover, connector nodes are located where brain activity is associated with many different cognitive functions. Connector nodes potentially play a role in between-module communication that maintains the modular function of the brain. Together, these findings provide a network account of the brain's modular yet integrated implementation of cognitive functions.

  3. Unveiling the mystery of visual information processing in human brain.

    Science.gov (United States)

    Diamant, Emanuel

    2008-08-15

    It is generally accepted that human vision is an extremely powerful information processing system that facilitates our interaction with the surrounding world. However, despite extended and extensive research efforts, which encompass many exploration fields, the underlying fundamentals and operational principles of visual information processing in human brain remain unknown. We still are unable to figure out where and how along the path from eyes to the cortex the sensory input perceived by the retina is converted into a meaningful object representation, which can be consciously manipulated by the brain. Studying the vast literature considering the various aspects of brain information processing, I was surprised to learn that the respected scholarly discussion is totally indifferent to the basic keynote question: "What is information?" in general or "What is visual information?" in particular. In the old days, it was assumed that any scientific research approach has first to define its basic departure points. Why was it overlooked in brain information processing research remains a conundrum. In this paper, I am trying to find a remedy for this bizarre situation. I propose an uncommon definition of "information", which can be derived from Kolmogorov's Complexity Theory and Chaitin's notion of Algorithmic Information. Embracing this new definition leads to an inevitable revision of traditional dogmas that shape the state of the art of brain information processing research. I hope this revision would better serve the challenging goal of human visual information processing modeling.

  4. Human-specific transcriptional networks in the brain

    Science.gov (United States)

    Konopka, Genevieve; Friedrich, Tara; Davis-Turak, Jeremy; Winden, Kellen; Oldham, Michael C.; Gao, Fuying; Chen, Leslie; Wang, Guang-Zhong; Luo, Rui; Preuss, Todd M.; Geschwind, Daniel H.

    2013-01-01

    Summary Understanding human-specific patterns of brain gene expression and regulation can provide key insights into human brain evolution and speciation. Here, we use next generation sequencing, and Illumina and Affymetrix microarray platforms, to compare the transcriptome of human, chimpanzee, and macaque telencephalon. Our analysis reveals a predominance of genes differentially expressed within human frontal lobe and a striking increase in transcriptional complexity specific to the human lineage in the frontal lobe. In contrast, caudate nucleus gene expression is highly conserved. We also identify gene co-expression signatures related to either neuronal processes or neuropsychiatric diseases, including a human-specific module with CLOCK as its hub gene and another module enriched for neuronal morphological processes and genes co-expressed with FOXP2, a gene important for language evolution. These data demonstrate that transcriptional networks have undergone evolutionary remodeling even within a given brain region, providing a new window through which to view the foundation of uniquely human cognitive capacities. PMID:22920253

  5. Rock magnetism linked to human brain magnetite

    Science.gov (United States)

    Kirschvink, Joseph L.

    Magnetite has a long and distinguished career as one of the most important minerals in geophysics, as it is responsible for most of the remanent magnetization in marine sediments and the oceanic crust. It may come as a surprise to discover that it also ranks as the third or fourth most diverse mineral product formed biochemically by living organisms, and forms naturally in a variety of human tissues [Kirschvink et al., 1992].Magnetite was discovered in teeth of the Polyplacophora mollusks over 30 years ago, in magnetotactic bacteria nearly 20 years ago, in honey bees and homing pigeons nearly 15 years ago, but only recently in human tissue.

  6. Quantitative determinations and imaging in different structures of buried human bones from the XVIII-XIXth centuries by energy dispersive X-ray fluorescence - Postmortem evaluation.

    Science.gov (United States)

    Guimarães, D; Dias, A A; Carvalho, M; Carvalho, M L; Santos, J P; Henriques, F R; Curate, F; Pessanha, S

    2016-08-01

    In this work, a non-commercial triaxial geometry energy dispersive X-ray Fluorescence (EDXRF) setup and a benchtop µ-XRF system were used to identify postmortem contamination in buried bones. For two of the individuals, unusually high concentrations of Cu and Pb, but also Zn (in one individual) were observed. The pigments of the burial shroud coverings have been identified as the source of contamination. Accurate and precise quantitative results were obtained by nondestructive process using fundamental parameters method taking into account the matrix absorption effects. A total of 30 bones from 13 individuals, buried between the mid-XVIIIth to early XIXth centuries, were analyzed to study the elemental composition and elemental distribution. The bones were collected from a church in Almada (Portugal), called Ermida do Espírito Santo, located near the Tagus River and at the sea neighbourhood. The triaxial geometry setup was used to quantify Ca, Fe, Cu, Zn, Br, Sr and Pb of powder pressed bone pellets (n=9 for each bone). Cluster analysis was performed considering the elemental concentrations for the different bones. There was a clear association between some bones regarding Fe, Cu, Zn, Br and Pb content but not a categorization between cortical and trabecular bones. The elemental distribution of Cu, Zn and Pb were assessed by the benchtop μ-analysis, the M4 Tornado, based on a polycapillary system which provides multi-elemental 2D maps. The results showed that contamination was mostly on the surface of the bone confirming that it was related to the burial shroud covering the individuals. Copyright © 2016 Elsevier B.V. All rights reserved.

  7. [Research Advances in Postmortem Chemistry].

    Science.gov (United States)

    Han, Shun-qi; Qin, Zhi-qiang; Deng, Kai-fei; Zhang, Jian-hua; Liu, Ning-guo; Zou, Dong-hua; Li, Zheng-dong; Shao, Yu; Huang, Ping; Chen, Yi-jiu

    2015-08-01

    Postmortem chemistry is becoming more and more essential in routine forensic pathology and has made considerable progress over the past years. Biochemical analyses of vitreous humor, blood, urine and cerebrospinal fluid may provide important information in determining the cause of death or in elucidating forensic issues. Postmortem chemistry may be essential for the determination of cause of death when morphological methods (diabetes mellitus, alcoholic ketoacidosis and electrolytic disorders) cannot detect the pathophysiological changes involved in the death process. It can also provide many information in other forensic situations, including myocardial ischemia, sepsis, inflammation, infection, anaphylaxis and hormonal disturbances. The most recent relevant research advances on glucose metabolism, liver function, cardiac function, renal function, sepsis, inflammation, infection, anaphylaxis and hormonal aspect are hereby reviewed.

  8. Uncovering intrinsic modular organization of spontaneous brain activity in humans.

    Directory of Open Access Journals (Sweden)

    Yong He

    Full Text Available The characterization of topological architecture of complex brain networks is one of the most challenging issues in neuroscience. Slow (<0.1 Hz, spontaneous fluctuations of the blood oxygen level dependent (BOLD signal in functional magnetic resonance imaging are thought to be potentially important for the reflection of spontaneous neuronal activity. Many studies have shown that these fluctuations are highly coherent within anatomically or functionally linked areas of the brain. However, the underlying topological mechanisms responsible for these coherent intrinsic or spontaneous fluctuations are still poorly understood. Here, we apply modern network analysis techniques to investigate how spontaneous neuronal activities in the human brain derived from the resting-state BOLD signals are topologically organized at both the temporal and spatial scales. We first show that the spontaneous brain functional networks have an intrinsically cohesive modular structure in which the connections between regions are much denser within modules than between them. These identified modules are found to be closely associated with several well known functionally interconnected subsystems such as the somatosensory/motor, auditory, attention, visual, subcortical, and the "default" system. Specifically, we demonstrate that the module-specific topological features can not be captured by means of computing the corresponding global network parameters, suggesting a unique organization within each module. Finally, we identify several pivotal network connectors and paths (predominantly associated with the association and limbic/paralimbic cortex regions that are vital for the global coordination of information flow over the whole network, and we find that their lesions (deletions critically affect the stability and robustness of the brain functional system. Together, our results demonstrate the highly organized modular architecture and associated topological properties in

  9. Visual dictionaries as intermediate features in the human brain

    Directory of Open Access Journals (Sweden)

    Kandan eRamakrishnan

    2015-01-01

    Full Text Available The human visual system is assumed to transform low level visual features to object and scene representations via features of intermediate complexity. How the brain computationally represents intermediate features is still unclear. To further elucidate this, we compared the biologically plausible HMAX model and Bag of Words (BoW model from computer vision. Both these computational models use visual dictionaries, candidate features of intermediate complexity, to represent visual scenes, and the models have been proven effective in automatic object and scene recognition. These models however differ in the computation of visual dictionaries and pooling techniques. We investigated where in the brain and to what extent human fMRI responses to short video can be accounted for by multiple hierarchical levels of the HMAX and BoW models. Brain activity of 20 subjects obtained while viewing a short video clip was analyzed voxel-wise using a distance-based variation partitioning method. Results revealed that both HMAX and BoW explain a significant amount of brain activity in early visual regions V1, V2 and V3. However BoW exhibits more consistency across subjects in accounting for brain activity compared to HMAX. Furthermore, visual dictionary representations by HMAX and BoW explain significantly some brain activity in higher areas which are believed to process intermediate features. Overall our results indicate that, although both HMAX and BoW account for activity in the human visual system, the BoW seems to more faithfully represent neural responses in low and intermediate level visual areas of the brain.

  10. Chemical Probes for Visualizing Intact Animal and Human Brain Tissue.

    Science.gov (United States)

    Lai, Hei Ming; Ng, Wai-Lung; Gentleman, Steve M; Wu, Wutian

    2017-06-22

    Newly developed tissue clearing techniques can be used to render intact tissues transparent. When combined with fluorescent labeling technologies and optical sectioning microscopy, this allows visualization of fine structure in three dimensions. Gene-transfection techniques have proved very useful in visualizing cellular structures in animal models, but they are not applicable to human brain tissue. Here, we discuss the characteristics of an ideal chemical fluorescent probe for use in brain and other cleared tissues, and offer a comprehensive overview of currently available chemical probes. We describe their working principles and compare their performance with the goal of simplifying probe selection for neuropathologists and stimulating probe development by chemists. We propose several approaches for the development of innovative chemical labeling methods which, when combined with tissue clearing, have the potential to revolutionize how we study the structure and function of the human brain. Copyright © 2017 Elsevier Ltd. All rights reserved.

  11. Integration of letters and speech sounds in the human brain

    NARCIS (Netherlands)

    van Atteveldt, Nienke; Formisano, Elia; Goebel, Rainer; Blomert, Leo

    2004-01-01

    Most people acquire literacy skills with remarkable ease, even though the human brain is not evolutionarily adapted to this relatively new cultural phenomenon. Associations between letters and speech sounds form the basis of reading in alphabetic scripts. We investigated the functional neuroanatomy

  12. Quantitative MRI of the human brain at 7 tesla

    NARCIS (Netherlands)

    Polders, D.L.

    2012-01-01

    This thesis describes the implementation of quantitative MR methods in the human brain at 7 T. By highlighting the drawbacks and advantages of the increased field strength, the use of 7 T MRI for quantitative measurements in clinical research was demonstrated. Inhomogeneities in the transmitted RF

  13. Human brain evolution, theories of innovation, and lessons from the ...

    Indian Academy of Sciences (India)

    Home; Journals; Journal of Biosciences; Volume 29; Issue 3. Human brain evolution, theories of innovation, and lessons from the history of technology. Alfred Gierer. Perspectives Volume 29 Issue 3 September 2004 pp 235-244. Fulltext. Click here to view fulltext PDF. Permanent link:

  14. Protracted dendritic growth in the typically developing human amygdala and increased spine density in young ASD brains.

    Science.gov (United States)

    Weir, R K; Bauman, M D; Jacobs, B; Schumann, C M

    2018-02-01

    The amygdala is a medial temporal lobe structure implicated in social and emotional regulation. In typical development (TD), the amygdala continues to increase volumetrically throughout childhood and into adulthood, while other brain structures are stable or decreasing in volume. In autism spectrum disorder (ASD), the amygdala undergoes rapid early growth, making it volumetrically larger in children with ASD compared to TD children. Here we explore: (a) if dendritic arborization in the amygdala follows the pattern of protracted growth in TD and early overgrowth in ASD and (b), if spine density in the amygdala in ASD cases differs from TD from youth to adulthood. The amygdala from 32 postmortem human brains (7-46 years of age) were stained using a Golgi-Kopsch impregnation. Ten principal neurons per case were selected in the lateral nucleus and traced using Neurolucida software in their entirety. We found that both ASD and TD individuals show a similar pattern of increasing dendritic length with age well into adulthood. However, spine density is (a) greater in young ASD cases compared to age-matched TD controls (ASD age into adulthood, a phenomenon not found in TD. Therefore, by adulthood, there is no observable difference in spine density in the amygdala between ASD and TD age-matched adults (≥18 years old). Our findings highlight the unique growth trajectory of the amygdala and suggest that spine density may contribute to aberrant development and function of the amygdala in children with ASD. © 2017 Wiley Periodicals, Inc.

  15. Identifying topological motif patterns of human brain functional networks.

    Science.gov (United States)

    Wei, Yongbin; Liao, Xuhong; Yan, Chaogan; He, Yong; Xia, Mingrui

    2017-05-01

    Recent imaging connectome studies demonstrated that the human functional brain network follows an efficient small-world topology with cohesive functional modules and highly connected hubs. However, the functional motif patterns that represent the underlying information flow remain largely unknown. Here, we investigated motif patterns within directed human functional brain networks, which were derived from resting-state functional magnetic resonance imaging data with controlled confounding hemodynamic latencies. We found several significantly recurring motifs within the network, including the two-node reciprocal motif and five classes of three-node motifs. These recurring motifs were distributed in distinct patterns to support intra- and inter-module functional connectivity, which also promoted integration and segregation in network organization. Moreover, the significant participation of several functional hubs in the recurring motifs exhibited their critical role in global integration. Collectively, our findings highlight the basic architecture governing brain network organization and provide insight into the information flow mechanism underlying intrinsic brain activities. Hum Brain Mapp 38:2734-2750, 2017. © 2017 Wiley Periodicals, Inc. © 2017 Wiley Periodicals, Inc.

  16. Zika Virus Infects Human Fetal Brain Microglia and Induces Inflammation.

    Science.gov (United States)

    Lum, Fok-Moon; Low, Donovan K S; Fan, Yiping; Tan, Jeslin J L; Lee, Bernett; Chan, Jerry K Y; Rénia, Laurent; Ginhoux, Florent; Ng, Lisa F P

    2017-04-01

    The unprecedented reemergence of Zika virus (ZIKV) has startled the world with reports of increased microcephaly in Brazil. ZIKV can infect human neural progenitors and impair brain growth. However, direct evidence of ZIKV infection in human fetal brain tissues remains elusive. Investigations were performed with brain cell preparations obtained from 9 donors. Virus infectivity was assessed by detection of virus antigen by flow cytometry together with various hematopoietic cell surface markers. Virus replication was determined by viral RNA quantification. Cytokine levels in supernatant obtained from virus-infected fetal brain cells were measured simultaneously in microbead-based immunoassays. We also show that ZIKV infection was particularly evident in hematopoietic cells with microglia, the brain-resident macrophage population being one of the main targets. Infection induces high levels of proinflammatory immune mediators such as interleukin 6 (IL-6), tumor necrosis factor alpha (TNF-α), interleukin 1β (IL-1β), and monocyte chemotactic protein 1 (MCP-1). Our results highlight an important role for microglia and neuroinflammation during congenital ZIKV pathogenesis.

  17. Common genetic variants influence human subcortical brain structures

    Science.gov (United States)

    Hibar, Derrek P.; Stein, Jason L.; Renteria, Miguel E.; Arias-Vasquez, Alejandro; Desrivières, Sylvane; Jahanshad, Neda; Toro, Roberto; Wittfeld, Katharina; Abramovic, Lucija; Andersson, Micael; Aribisala, Benjamin S.; Armstrong, Nicola J.; Bernard, Manon; Bohlken, Marc M.; Boks, Marco P.; Bralten, Janita; Brown, Andrew A.; Chakravarty, M. Mallar; Chen, Qiang; Ching, Christopher R. K.; Cuellar-Partida, Gabriel; den Braber, Anouk; Giddaluru, Sudheer; Goldman, Aaron L.; Grimm, Oliver; Guadalupe, Tulio; Hass, Johanna; Woldehawariat, Girma; Holmes, Avram J.; Hoogman, Martine; Janowitz, Deborah; Jia, Tianye; Kim, Sungeun; Klein, Marieke; Kraemer, Bernd; Lee, Phil H.; Olde Loohuis, Loes M.; Luciano, Michelle; Macare, Christine; Mather, Karen A.; Mattheisen, Manuel; Milaneschi, Yuri; Nho, Kwangsik; Papmeyer, Martina; Ramasamy, Adaikalavan; Risacher, Shannon L.; Roiz-Santiañez, Roberto; Rose, Emma J.; Salami, Alireza; Sämann, Philipp G.; Schmaal, Lianne; Schork, Andrew J.; Shin, Jean; Strike, Lachlan T.; Teumer, Alexander; van Donkelaar, Marjolein M. J.; van Eijk, Kristel R.; Walters, Raymond K.; Westlye, Lars T.; Whelan, Christopher D.; Winkler, Anderson M.; Zwiers, Marcel P.; Alhusaini, Saud; Athanasiu, Lavinia; Ehrlich, Stefan; Hakobjan, Marina M. H.; Hartberg, Cecilie B.; Haukvik, Unn K.; Heister, Angelien J. G. A. M.; Hoehn, David; Kasperaviciute, Dalia; Liewald, David C. M.; Lopez, Lorna M.; Makkinje, Remco R. R.; Matarin, Mar; Naber, Marlies A. M.; McKay, D. Reese; Needham, Margaret; Nugent, Allison C.; Pütz, Benno; Royle, Natalie A.; Shen, Li; Sprooten, Emma; Trabzuni, Daniah; van der Marel, Saskia S. L.; van Hulzen, Kimm J. E.; Walton, Esther; Wolf, Christiane; Almasy, Laura; Ames, David; Arepalli, Sampath; Assareh, Amelia A.; Bastin, Mark E.; Brodaty, Henry; Bulayeva, Kazima B.; Carless, Melanie A.; Cichon, Sven; Corvin, Aiden; Curran, Joanne E.; Czisch, Michael; de Zubicaray, Greig I.; Dillman, Allissa; Duggirala, Ravi; Dyer, Thomas D.; Erk, Susanne; Fedko, Iryna O.; Ferrucci, Luigi; Foroud, Tatiana M.; Fox, Peter T.; Fukunaga, Masaki; Gibbs, J. Raphael; Göring, Harald H. H.; Green, Robert C.; Guelfi, Sebastian; Hansell, Narelle K.; Hartman, Catharina A.; Hegenscheid, Katrin; Heinz, Andreas; Hernandez, Dena G.; Heslenfeld, Dirk J.; Hoekstra, Pieter J.; Holsboer, Florian; Homuth, Georg; Hottenga, Jouke-Jan; Ikeda, Masashi; Jack, Clifford R.; Jenkinson, Mark; Johnson, Robert; Kanai, Ryota; Keil, Maria; Kent, Jack W.; Kochunov, Peter; Kwok, John B.; Lawrie, Stephen M.; Liu, Xinmin; Longo, Dan L.; McMahon, Katie L.; Meisenzahl, Eva; Melle, Ingrid; Mohnke, Sebastian; Montgomery, Grant W.; Mostert, Jeanette C.; Mühleisen, Thomas W.; Nalls, Michael A.; Nichols, Thomas E.; Nilsson, Lars G.; Nöthen, Markus M.; Ohi, Kazutaka; Olvera, Rene L.; Perez-Iglesias, Rocio; Pike, G. Bruce; Potkin, Steven G.; Reinvang, Ivar; Reppermund, Simone; Rietschel, Marcella; Romanczuk-Seiferth, Nina; Rosen, Glenn D.; Rujescu, Dan; Schnell, Knut; Schofield, Peter R.; Smith, Colin; Steen, Vidar M.; Sussmann, Jessika E.; Thalamuthu, Anbupalam; Toga, Arthur W.; Traynor, Bryan J.; Troncoso, Juan; Turner, Jessica A.; Valdés Hernández, Maria C.; van ’t Ent, Dennis; van der Brug, Marcel; van der Wee, Nic J. A.; van Tol, Marie-Jose; Veltman, Dick J.; Wassink, Thomas H.; Westman, Eric; Zielke, Ronald H.; Zonderman, Alan B.; Ashbrook, David G.; Hager, Reinmar; Lu, Lu; McMahon, Francis J.; Morris, Derek W.; Williams, Robert W.; Brunner, Han G.; Buckner, Randy L.; Buitelaar, Jan K.; Cahn, Wiepke; Calhoun, Vince D.; Cavalleri, Gianpiero L.; Crespo-Facorro, Benedicto; Dale, Anders M.; Davies, Gareth E.; Delanty, Norman; Depondt, Chantal; Djurovic, Srdjan; Drevets, Wayne C.; Espeseth, Thomas; Gollub, Randy L.; Ho, Beng-Choon; Hoffmann, Wolfgang; Hosten, Norbert; Kahn, René S.; Le Hellard, Stephanie; Meyer-Lindenberg, Andreas; Müller-Myhsok, Bertram; Nauck, Matthias; Nyberg, Lars; Pandolfo, Massimo; Penninx, Brenda W. J. H.; Roffman, Joshua L.; Sisodiya, Sanjay M.; Smoller, Jordan W.; van Bokhoven, Hans; van Haren, Neeltje E. M.; Völzke, Henry; Walter, Henrik; Weiner, Michael W.; Wen, Wei; White, Tonya; Agartz, Ingrid; Andreassen, Ole A.; Blangero, John; Boomsma, Dorret I.; Brouwer, Rachel M.; Cannon, Dara M.; Cookson, Mark R.; de Geus, Eco J. C.; Deary, Ian J.; Donohoe, Gary; Fernández, Guillén; Fisher, Simon E.; Francks, Clyde; Glahn, David C.; Grabe, Hans J.; Gruber, Oliver; Hardy, John; Hashimoto, Ryota; Hulshoff Pol, Hilleke E.; Jönsson, Erik G.; Kloszewska, Iwona; Lovestone, Simon; Mattay, Venkata S.; Mecocci, Patrizia; McDonald, Colm; McIntosh, Andrew M.; Ophoff, Roel A.; Paus, Tomas; Pausova, Zdenka; Ryten, Mina; Sachdev, Perminder S.; Saykin, Andrew J.; Simmons, Andy; Singleton, Andrew; Soininen, Hilkka; Wardlaw, Joanna M.; Weale, Michael E.; Weinberger, Daniel R.; Adams, Hieab H. H.; Launer, Lenore J.; Seiler, Stephan; Schmidt, Reinhold; Chauhan, Ganesh; Satizabal, Claudia L.; Becker, James T.; Yanek, Lisa; van der Lee, Sven J.; Ebling, Maritza; Fischl, Bruce; Longstreth, W. T.; Greve, Douglas; Schmidt, Helena; Nyquist, Paul; Vinke, Louis N.; van Duijn, Cornelia M.; Xue, Luting; Mazoyer, Bernard; Bis, Joshua C.; Gudnason, Vilmundur; Seshadri, Sudha; Ikram, M. Arfan; Martin, Nicholas G.; Wright, Margaret J.; Schumann, Gunter; Franke, Barbara; Thompson, Paul M.; Medland, Sarah E.

    2015-01-01

    The highly complex structure of the human brain is strongly shaped by genetic influences1. Subcortical brain regions form circuits with cortical areas to coordinate movement2, learning, memory3 and motivation4, and altered circuits can lead to abnormal behaviour and disease2. To investigate how common genetic variants affect the structure of these brain regions, here we conduct genome-wide association studies of the volumes of seven subcortical regions and the intracranial volume derived from magnetic resonance images of 30,717 individuals from 50 cohorts. We identify five novel genetic variants influencing the volumes of the putamen and caudate nucleus. We also find stronger evidence for three loci with previously established influences on hippocampal volume5 and intracranial volume6. These variants show specific volumetric effects on brain structures rather than global effects across structures. The strongest effects were found for the putamen, where a novel intergenic locus with replicable influence on volume (rs945270; P = 1.08 × 10−33; 0.52% variance explained) showed evidence of altering the expression of the KTN1 gene in both brain and blood tissue. Variants influencing putamen volume clustered near developmental genes that regulate apoptosis, axon guidance and vesicle transport. Identification of these genetic variants provides insight into the causes of variability inhuman brain development, and may help to determine mechanisms of neuropsychiatric dysfunction. PMID:25607358

  18. Topological isomorphisms of human brain and financial market networks.

    Science.gov (United States)

    Vértes, Petra E; Nicol, Ruth M; Chapman, Sandra C; Watkins, Nicholas W; Robertson, Duncan A; Bullmore, Edward T

    2011-01-01

    Although metaphorical and conceptual connections between the human brain and the financial markets have often been drawn, rigorous physical or mathematical underpinnings of this analogy remain largely unexplored. Here, we apply a statistical and graph theoretic approach to the study of two datasets - the time series of 90 stocks from the New York stock exchange over a 3-year period, and the fMRI-derived time series acquired from 90 brain regions over the course of a 10-min-long functional MRI scan of resting brain function in healthy volunteers. Despite the many obvious substantive differences between these two datasets, graphical analysis demonstrated striking commonalities in terms of global network topological properties. Both the human brain and the market networks were non-random, small-world, modular, hierarchical systems with fat-tailed degree distributions indicating the presence of highly connected hubs. These properties could not be trivially explained by the univariate time series statistics of stock price returns. This degree of topological isomorphism suggests that brains and markets can be regarded broadly as members of the same family of networks. The two systems, however, were not topologically identical. The financial market was more efficient and more modular - more highly optimized for information processing - than the brain networks; but also less robust to systemic disintegration as a result of hub deletion. We conclude that the conceptual connections between brains and markets are not merely metaphorical; rather these two information processing systems can be rigorously compared in the same mathematical language and turn out often to share important topological properties in common to some degree. There will be interesting scientific arbitrage opportunities in further work at the graph-theoretically mediated interface between systems neuroscience and the statistical physics of financial markets.

  19. The song system of the human brain.

    Science.gov (United States)

    Brown, Steven; Martinez, Michael J; Hodges, Donald A; Fox, Peter T; Parsons, Lawrence M

    2004-08-01

    Although sophisticated insights have been gained into the neurobiology of singing in songbirds, little comparable knowledge exists for humans, the most complex singers in nature. Human song complexity is evidenced by the capacity to generate both richly structured melodies and coordinated multi-part harmonizations. The present study aimed to elucidate this multi-faceted vocal system by using 15O-water positron emission tomography to scan "listen and respond" performances of amateur musicians either singing repetitions of novel melodies, singing harmonizations with novel melodies, or vocalizing monotonically. Overall, major blood flow increases were seen in the primary and secondary auditory cortices, primary motor cortex, frontal operculum, supplementary motor area, insula, posterior cerebellum, and basal ganglia. Melody repetition and harmonization produced highly similar patterns of activation. However, whereas all three tasks activated secondary auditory cortex (posterior Brodmann Area 22), only melody repetition and harmonization activated the planum polare (BA 38). This result implies that BA 38 is responsible for an even higher level of musical processing than BA 22. Finally, all three of these "listen and respond" tasks activated the frontal operculum (Broca's area), a region involved in cognitive/motor sequence production and imitation, thereby implicating it in musical imitation and vocal learning.

  20. Postmortem imaging of blood and its characteristics using MSCT and MRI.

    Science.gov (United States)

    Jackowski, C; Thali, M; Aghayev, E; Yen, K; Sonnenschein, M; Zwygart, K; Dirnhofer, R; Vock, P

    2006-07-01

    The rapid development of computed tomography (CT) and magnetic resonance imaging (MRI) led to the introduction and establishment in postmortem investigations. The objectives of this preliminary study were to describe the imaging appearances of the early postmortem changes of blood after cessation of the circulation, such as sedimentation, postmortem clotting, and internal livores, and to give a few first suggestions on how to differentiate them from other forensic findings. In the Virtopsy project, 95 human corpses underwent postmortem imaging by CT and MRI prior to traditional autopsy and therefore 44 cases have been investigated in this study. Postmortem alterations as well as the forensic relevant findings of the blood, such as internal or subcutaneous bleedings, are presented on the basis of their imaging appearances in multislice CT and MRI.

  1. 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.

  2. Brain lactate metabolism in humans with subarachnoid hemorrhage.

    Science.gov (United States)

    Oddo, Mauro; Levine, Joshua M; Frangos, Suzanne; Maloney-Wilensky, Eileen; Carrera, Emmanuel; Daniel, Roy T; Levivier, Marc; Magistretti, Pierre J; LeRoux, Peter D

    2012-05-01

    Lactate is central for the regulation of brain metabolism and is an alternative substrate to glucose after injury. Brain lactate metabolism in patients with subarachnoid hemorrhage has not been fully elucidated. Thirty-one subarachnoid hemorrhage patients monitored with cerebral microdialysis (CMD) and brain oxygen (PbtO(2)) were studied. Samples with elevated CMD lactate (>4 mmol/L) were matched to PbtO(2) and CMD pyruvate and categorized as hypoxic (PbtO(2) 119 μmol/L) versus nonhyperglycolytic. Median per patient samples with elevated CMD lactate was 54% (interquartile range, 11%-80%). Lactate elevations were more often attributable to cerebral hyperglycolysis (78%; interquartile range, 5%-98%) than brain hypoxia (11%; interquartile range, 4%-75%). Mortality was associated with increased percentage of samples with elevated lactate and brain hypoxia (28% [interquartile range 9%-95%] in nonsurvivors versus 9% [interquartile range 3%-17%] in survivors; P=0.02) and lower percentage of elevated lactate and cerebral hyperglycolysis (13% [interquartile range, 1%-87%] versus 88% [interquartile range, 27%-99%]; P=0.07). Cerebral hyperglycolytic lactate production predicted good 6-month outcome (odds ratio for modified Rankin Scale score, 0-3 1.49; CI, 1.08-2.05; P=0.016), whereas increased lactate with brain hypoxia was associated with a reduced likelihood of good outcome (OR, 0.78; CI, 0.59-1.03; P=0.08). Brain lactate is frequently elevated in subarachnoid hemorrhage patients, predominantly because of hyperglycolysis rather than hypoxia. A pattern of increased cerebral hyperglycolytic lactate was associated with good long-term recovery. Our data suggest that lactate may be used as an aerobic substrate by the injured human brain.

  3. Dentatorubrothalamic tract localization with postmortem MR diffusion tractography compared to histological 3D reconstruction.

    Science.gov (United States)

    Mollink, J; van Baarsen, K M; Dederen, P J W C; Foxley, S; Miller, K L; Jbabdi, S; Slump, C H; Grotenhuis, J A; Kleinnijenhuis, M; van Cappellen van Walsum, A M

    2016-09-01

    Diffusion-weighted imaging (DWI) tractography is a technique with great potential to characterize the in vivo anatomical position and integrity of white matter tracts. Tractography, however, remains an estimation of white matter tracts, and false-positive and false-negative rates are not available. The goal of the present study was to compare postmortem tractography of the dentatorubrothalamic tract (DRTT) by its 3D histological reconstruction, to estimate the reliability of the tractography algorithm in this specific tract. Recent studies have shown that the cerebellum is involved in cognitive, language and emotional functions besides its role in motor control. However, the exact working mechanism of the cerebellum is still to be elucidated. As the DRTT is the main output tract it is of special interest for the neuroscience and clinical community. A postmortem human brain specimen was scanned on a 7T MRI scanner using a diffusion-weighted steady-state free precession sequence. Tractography was performed with PROBTRACKX. The specimen was subsequently serially sectioned and stained for myelin using a modified Heidenhain-Woelke staining. Image registration permitted the 3D reconstruction of the histological sections and comparison with MRI. The spatial concordance between the two modalities was evaluated using ROC analysis and a similarity index (SI). ROC curves showed a high sensitivity and specificity in general. Highest measures were observed in the superior cerebellar peduncle with an SI of 0.72. Less overlap was found in the decussation of the DRTT at the level of the mesencephalon. The study demonstrates high spatial accuracy of postmortem probabilistic tractography of the DRTT when compared to a 3D histological reconstruction. This gives hopeful prospect for studying structure-function correlations in patients with cerebellar disorders using tractography of the DRTT.

  4. Xanthine oxidase activity regulates human embryonic brain cells growth

    Directory of Open Access Journals (Sweden)

    Kevorkian G. A.

    2011-10-01

    Full Text Available Aim. Involvement of Xanthine Oxidase (XO; EC1.1.3.22 in cellular proliferation and differentiation has been suggested by the numerous investigations. We have proposed that XO might have undoubtedly important role during the development, maturation as well as the death of human embryos brain cells. Methods. Human abortion material was utilized for the cultivation of brain cells (E90. XO activity was measured by the formation of uric acid in tissue. Cell death was detected by the utility of Trypan Blue dye. Results. Allopurinol suppressed the XO activity in the brain tissue (0.12 ± 0.02; 0.20 ± 0.03 resp., p < 0.05. On day 12th the number of cells in the culture treated with the Allopurinol at the early stage of development was higher in comparison with the Control (2350.1 ± 199.0 vs 2123 ± 96 and higher in comparison with the late period of treatment (1479.6 ± 103.8, p < < 0.05. In all groups, the number of the dead cells was less than in Control, indicating the protective nature of Allopurinol as an inhibitor of XO. Conclusions. Allopurinol initiates cells proliferation in case of the early treatment of the human brain derived cell culture whereas at the late stages it has an opposite effect.

  5. The nicotinic cholinergic system function in the human brain.

    Science.gov (United States)

    Nees, Frauke

    2015-09-01

    Research on the nicotinic cholinergic system function in the brain was previously mainly derived from animal studies, yet, research in humans is growing. Up to date, findings allow significant advances on the understanding of nicotinic cholinergic effects on human cognition, emotion and behavior using a range of functional brain imaging approaches such as pharmacological functional magnetic resonance imaging or positron emission tomography. Studies provided insights across various mechanistic psychological domains using different tasks as well as at rest in both healthy individuals and patient populations, with so far partly mixed results reporting both enhancements and decrements of neural activity related to the nicotinic cholinergic system. Moreover, studies on the relation between brain structure and the nicotinic cholinergic system add important information in this context. The present review summarizes the current status of human brain imaging studies and presents the findings within a theoretical and clinical perspective as they may be useful not only for an advancement of the understanding of basic nicotinic cholinergic-related mechanisms, but also for the development and integration of psychological and pharmacological treatment approaches. Patterns of functional neuroanatomy and neural circuitry across various cognitive and emotional domains may be used as neuropsychological markers of mental disorders such as addiction, Alzheimer's disease, Parkinson disease or schizophrenia, where nicotinic cholinergic system changes are characteristic. This article is part of the Special Issue entitled 'The Nicotinic Acetylcholine Receptor: From Molecular Biology to Cognition'. Copyright © 2014 Elsevier Ltd. All rights reserved.

  6. Mapping the calcitonin receptor in human brain stem

    DEFF Research Database (Denmark)

    Bower, Rebekah L; Eftekhari, Sajedeh; Waldvogel, Henry J

    2016-01-01

    understanding of these hormone systems by mapping CTR expression in the human brain stem, specifically the medulla oblongata. Widespread CTR-like immunoreactivity was observed throughout the medulla. Dense CTR staining was noted in several discrete nuclei, including the nucleus of the solitary tract...... receptors (AMY) are a heterodimer formed by the coexpression of CTR with receptor activity-modifying proteins (RAMPs). CTR with RAMP1 responds potently to both amylin and CGRP. The brain stem is a major site of action for circulating amylin and is a rich site of CGRP binding. This study aimed to enhance our...

  7. Human cadaver brain infusion model for neurosurgical training.

    Science.gov (United States)

    Olabe, Jon; Olabe, Javier; Sancho, Vidal

    2009-12-01

    Microneurosurgical technique and anatomical knowledge require extensive laboratory training before mastering these skills. There are diverse training models based on synthetic materials, anesthetized animals, cadaver animals, or human cadaver. Human cadaver models are especially beneficial because they are the closest to live surgery with the greatest disadvantage of lacking hemodynamic factors. We developed the "brain infusion model" to provide a simple but realistic training method minimizing animal use or needs for special facilities. Four human cadaveric brains donated for educational purposes were explanted at autopsy. Carotids and vertebral arteries were cannulated with plastic tubes and fixed with suture. Water was flushed through the tubings until the whole arterial vasculature was observed as clean. The cannulated specimens were fixed with formaldehyde. Tap water infusion at a flow rate of 10 L/h was infused through the arterial tubings controlled with a drip regulator filling the arterial tree and leaking into the interstitial and cisternal space. Multiple microneurosurgical procedures were performed by 4 trainees. Cisternal and vascular dissection was executed in a very realistic fashion. Bypass anastomosis was created as well as aneurysm simulation with venous pouches. Vessel and aneurysm clipping and rupture situations were emulated and solution techniques were trained. Standard microsurgical laboratories regularly have scarce opportunities for working with decapitated human cadaver heads but could have human brains readily available. The human brain infusion model presents a realistic microneurosurgical training method. It is inexpensive and easy to set up. Such simplicity provides the adequate environment for developing microsurgical techniques. Copyright 2009 Elsevier Inc. All rights reserved.

  8. Comparison of the binding of the irreversible monoamine oxidase tracers, [{sup 11}C]clorgyline and [{sup 11}C]l-deprenyl in brain and peripheral organs in humans

    Energy Technology Data Exchange (ETDEWEB)

    Fowler, Joanna S. E-mail: fowler@bnl.gov; Logan, Jean; Wang, Gene-Jack; Volkow, Nora D.; Telang, Frank; Ding Yushin; Shea, Colleen; Garza, Victor; Xu Youwen; Li Zizhong; Alexoff, David; Vaska, Paul; Ferrieri, Richard; Schlyer, David; Zhu Wei; John Gatley, S

    2004-04-01

    The monoamine oxidase A and B (MAO A and B) radiotracers [{sup 11}C]clorgyline (CLG) and [{sup 11}C]L-deprenyl (DEP) and their deuterium labeled counterparts (CLG-D and DEP-D) were compared to determine whether their distribution and kinetics in humans are consistent with their physical, chemical and pharmacological properties and the reported ratios of MAO A:MAO B in post-mortem human tissues. Irreversible binding was consistently higher for DEP in brain, heart, kidneys and spleen but not lung where CLG >DEP and not in thyroid where there is no DEP binding. The generally higher DEP binding is consistent with its higher enzyme affinity and larger free fraction in plasma while differences in regional distribution for CLG and DEP in brain, heart, thyroid and lungs are consistent with different relative ratios of MAO A and B in humans.

  9. A human-specific de novo protein-coding gene associated with human brain functions.

    Directory of Open Access Journals (Sweden)

    Chuan-Yun Li

    2010-03-01

    Full Text Available To understand whether any human-specific new genes may be associated with human brain functions, we computationally screened the genetic vulnerable factors identified through Genome-Wide Association Studies and linkage analyses of nicotine addiction and found one human-specific de novo protein-coding gene, FLJ33706 (alternative gene symbol C20orf203. Cross-species analysis revealed interesting evolutionary paths of how this gene had originated from noncoding DNA sequences: insertion of repeat elements especially Alu contributed to the formation of the first coding exon and six standard splice junctions on the branch leading to humans and chimpanzees, and two subsequent substitutions in the human lineage escaped two stop codons and created an open reading frame of 194 amino acids. We experimentally verified FLJ33706's mRNA and protein expression in the brain. Real-Time PCR in multiple tissues demonstrated that FLJ33706 was most abundantly expressed in brain. Human polymorphism data suggested that FLJ33706 encodes a protein under purifying selection. A specifically designed antibody detected its protein expression across human cortex, cerebellum and midbrain. Immunohistochemistry study in normal human brain cortex revealed the localization of FLJ33706 protein in neurons. Elevated expressions of FLJ33706 were detected in Alzheimer's brain samples, suggesting the role of this novel gene in human-specific pathogenesis of Alzheimer's disease. FLJ33706 provided the strongest evidence so far that human-specific de novo genes can have protein-coding potential and differential protein expression, and be involved in human brain functions.

  10. The Value of Postmortem Microbiology Cultures

    OpenAIRE

    Riedel, Stefan

    2014-01-01

    Since the inception of evidence-based scientific concepts in medicine in the 19th century, the utility of postmortem microbiologic examinations has been a topic of controversy. For every study describing a lack of correlation between antemortem clinical and laboratory findings and postmortem culture results, there is equal evidence from other studies that indicates at least some limited utility in select cases. While the contributions of autopsies and postmortem microbiologic examinations in ...

  11. Brain-Computer Interfaces Revolutionizing Human-Computer Interaction

    CERN Document Server

    Graimann, Bernhard; Allison, Brendan

    2010-01-01

    A brain-computer interface (BCI) establishes a direct output channel between the human brain and external devices. BCIs infer user intent via direct measures of brain activity and thus enable communication and control without movement. This book, authored by experts in the field, provides an accessible introduction to the neurophysiological and signal-processing background required for BCI, presents state-of-the-art non-invasive and invasive approaches, gives an overview of current hardware and software solutions, and reviews the most interesting as well as new, emerging BCI applications. The book is intended not only for students and young researchers, but also for newcomers and other readers from diverse backgrounds keen to learn about this vital scientific endeavour.

  12. Is the Social Brain Theory Applicable to Human Individual Differences? Relationship between Sociability Personality Dimension and Brain Size

    Directory of Open Access Journals (Sweden)

    Klára Horváth

    2011-04-01

    Full Text Available Our study intends to examine whether the social brain theory is applicable to human individual differences. According to the social brain theory primates have larger brains as it could be expected from their body sizes due to the adaptation to a more complex social life. Regarding humans there were few studies about the relationship between theory of mind and frontal and temporal brain lobes. We hypothesized that these brain lobes, as well as the whole cerebrum and neocortex are in connection with the Sociability personality dimension that is associated with individuals' social lives. Our findings support this hypothesis as Sociability correlated positively with the examined brain structures if we control the effects of body size differences and age. These results suggest that the social brain theory can be extended to human interindividual differences and they have some implications to personality psychology too.

  13. Is the social brain theory applicable to human individual differences? Relationship between sociability personality dimension and brain size.

    Science.gov (United States)

    Horváth, Klára; Martos, János; Mihalik, Béla; Bódizs, Róbert

    2011-06-17

    Our study intends to examine whether the social brain theory is applicable to human individual differences. According to the social brain theory primates have larger brains as it could be expected from their body sizes due to the adaptation to a more complex social life. Regarding humans there were few studies about the relationship between theory of mind and frontal and temporal brain lobes. We hypothesized that these brain lobes, as well as the whole cerebrum and neocortex are in connection with the Sociability personality dimension that is associated with individuals' social lives. Our findings support this hypothesis as Sociability correlated positively with the examined brain structures if we control the effects of body size differences and age. These results suggest that the social brain theory can be extended to human interindividual differences and they have some implications to personality psychology too.

  14. Translational Pharmacology of the Metabotropic Glutamate 2 Receptor-Preferring Agonist LY2812223 in the Animal and Human Brain.

    Science.gov (United States)

    Felder, Christian C; Schober, Douglas A; Tu, Yuan; Quets, Anne; Xiao, Hongling; Watt, Marla; Siuda, Ed; Nisenbaum, Eric; Xiang, Chuanxi; Heinz, Beverly; Prieto, Lourdes; McKinzie, David L; Monn, James A

    2017-04-01

    LY2812223 [(1 R ,2 S ,4 R ,5 R ,6 R )-2-amino-4-(1 H -1,2,4-triazol-3-ylsulfanyl)bicyclo[3.1.0]hexane-2,6-dicarboxylic acid] was identified via structure-activity studies arising from the potent metabotropic glutamate mGlu2/3 receptor agonist LY354740 [(+)-2-aminobicyclo[3.1.0] hexane-2,6-dicarboxylic acid] as an mGlu2-preferring agonist. This pharmacology was determined using stably transfected cells containing either the human mGlu2 or mGlu3 receptor. We extended the pharmacological evaluation of LY2812223 to native brain tissues derived from relevant species used for preclinical drug development as well as human postmortem brain tissue. This analysis was conducted to ensure pharmacological translation from animals to human subjects in subsequent clinical studies. A guanosine 5'- O -(3-[ 35 S]thio)triphosphate (GTP γ S) functional binding assay, a method for measuring G i -coupled signaling that is inherent to the group 2 mGlu receptors, was used to evaluate LY2812223 pharmacology of native mGlu receptors in mouse, rat, nonhuman primate, and human cortical brain tissue samples. In native tissue membranes, LY2812223 unexpectedly acted as a partial agonist across all species tested. Activity of LY2812223 was lost in cortical membranes collected from mGlu2 knockout mice, but not those from mGlu3 knockout mice, providing additional support for mGlu2-preferring activity. Other signal transduction assays were used for comparison with the GTP binding assay (cAMP, calcium mobilization, and dynamic mass redistribution). In ectopic cell line-based assays, LY2812223 displayed near maximal agonist responses at the mGlu2 receptor across all assay formats, while it showed no functional agonist activity at the mGlu3 receptor except in the cAMP assay. In native brain slices or membranes that express both mGlu2 and mGlu3 receptors, LY2812223 displayed unexpected partial agonist activity, which may suggest a functional interplay between these receptor subtypes in the brain

  15. Deformation of the human brain induced by mild acceleration.

    Science.gov (United States)

    Bayly, P V; Cohen, T S; Leister, E P; Ajo, D; Leuthardt, E C; Genin, G M

    2005-08-01

    Rapid deformation of brain matter caused by skull acceleration is most likely the cause of concussion, as well as more severe traumatic brain injury (TBI). The inability to measure deformation directly has led to disagreement and confusion about the biomechanics of concussion and TBI. In the present study, brain deformation in human volunteers was measured directly during mild, but rapid, deceleration of the head (20-30 m/sec2 peak, approximately 40 msec duration), using an imaging technique originally developed to measure cardiac deformation. Magnetic resonance image sequences with imposed "tag" lines were obtained at high frame rates by repeating the deceleration and acquiring a subset of image data each repetition. Displacements of points on tag lines were used to estimate the Lagrangian strain tensor field. Qualitative (visual) and quantitative (strain) results illustrate clearly the deformation of brain matter due to occipital deceleration. Strains of 0.02-0.05 were typical during these events (0.05 strain corresponds roughly to a 5% change in the dimension of a local tissue element). Notably, compression in frontal regions and stretching in posterior regions were observed. The motion of the brain appears constrained by structures at the frontal base of the skull; it must pull away from such constraints before it can compress against the occipital bone. This mechanism is consistent with observations of contrecoup injury in occipital impact.

  16. Pulsatile cerebrospinal fluid dynamics in the human brain.

    Science.gov (United States)

    Linninger, Andreas A; Tsakiris, Cristian; Zhu, David C; Xenos, Michalis; Roycewicz, Peter; Danziger, Zachary; Penn, Richard

    2005-04-01

    Disturbances of the cerebrospinal fluid (CSF) flow in the brain can lead to hydrocephalus, a condition affecting thousands of people annually in the US. Considerable controversy exists about fluid and pressure dynamics, and about how the brain responds to changes in flow patterns and compression in hydrocephalus. This paper presents a new model based on the first principles of fluid mechanics. This model of fluid-structure interactions predicts flows and pressures throughout the brain's ventricular pathways consistent with both animal intracranial pressure (ICP) measurements and human CINE phase-contrast magnetic resonance imaging data. The computations provide approximations of the tissue deformations of the brain parenchyma. The model also quantifies the pulsatile CSF motion including flow reversal in the aqueduct as well as the changes in ICPs due to brain tissue compression. It does not require the existence of large transmural pressure differences as the force for ventricular expansion. Finally, the new model gives an explanation of communicating hydrocephalus and the phenomenon of asymmetric hydrocephalus.

  17. The maternal brain and its plasticity in humans.

    Science.gov (United States)

    Kim, Pilyoung; Strathearn, Lane; Swain, James E

    2016-01-01

    This article is part of a Special Issue "Parental Care". Early mother-infant relationships play important roles in infants' optimal development. New mothers undergo neurobiological changes that support developing mother-infant relationships regardless of great individual differences in those relationships. In this article, we review the neural plasticity in human mothers' brains based on functional magnetic resonance imaging (fMRI) studies. First, we review the neural circuits that are involved in establishing and maintaining mother-infant relationships. Second, we discuss early postpartum factors (e.g., birth and feeding methods, hormones, and parental sensitivity) that are associated with individual differences in maternal brain neuroplasticity. Third, we discuss abnormal changes in the maternal brain related to psychopathology (i.e., postpartum depression, posttraumatic stress disorder, substance abuse) and potential brain remodeling associated with interventions. Last, we highlight potentially important future research directions to better understand normative changes in the maternal brain and risks for abnormal changes that may disrupt early mother-infant relationships. Copyright © 2015 Elsevier Inc. All rights reserved.

  18. Mapping human brain lesions and their functional consequences.

    Science.gov (United States)

    Karnath, Hans-Otto; Sperber, Christoph; Rorden, Christopher

    2018-01-15

    Neuroscience has a long history of inferring brain function by examining the relationship between brain injury and subsequent behavioral impairments. The primary advantage of this method over correlative methods is that it can tell us if a certain brain region is necessary for a given cognitive function. In addition, lesion-based analyses provide unique insights into clinical deficits. In the last decade, statistical voxel-based lesion behavior mapping (VLBM) emerged as a powerful method for understanding the architecture of the human brain. This review illustrates how VLBM improves our knowledge of functional brain architecture, as well as how it is inherently limited by its mass-univariate approach. A wide array of recently developed methods appear to supplement traditional VLBM. This paper provides an overview of these new methods, including the use of specialized imaging modalities, the combination of structural imaging with normative connectome data, as well as multivariate analyses of structural imaging data. We see these new methods as complementing rather than replacing traditional VLBM, providing synergistic tools to answer related questions. Finally, we discuss the potential for these methods to become established in cognitive neuroscience and in clinical applications. Copyright © 2017 Elsevier Inc. All rights reserved.

  19. Human Brain Stem Structures Respond Differentially to Noxious Heat

    Directory of Open Access Journals (Sweden)

    Alexander eRitter

    2013-09-01

    Full Text Available Concerning the physiological correlates of pain, the brain stem is considered to be one core region that is activated by noxious input. In animal studies, different slopes of skin heating (SSH with noxious heat led to activation in different columns of the midbrain periaqueductal grey (PAG. The present study aimed at finding a method for differentiating structures in PAG and other brain stem structures, which are associated with different qualities of pain in humans according to the structures that were associated with different behavioral significances to noxious thermal stimulation in animals. Brain activity was studied by fMRI in healthy subjects in response to steep and shallow SSH with noxious heat. We found differential activation to different SSH in the PAG and the rostral ventromedial medulla (RVM. In a second experiment we demonstrate that the different SSH were associated with different pain qualities. Our experiments provide evidence that brainstem structures, i.e. the PAG and the RVM, become differentially activated by different SSH. Therefore, different SSH can be utilized when brain stem structures are investigated and when it is aimed to activate these structures differentially. Moreover, percepts of first pain were elicited by shallow SSH whereas percepts of second pain were elicited by steep SSH. The stronger activation of these brain stem structures to SSH, eliciting percepts of second vs. first pain, might be of relevance for activating different coping strategies in response to the noxious input with the two types of SSH.

  20. The Speculative Neuroscience of the Future Human Brain

    Directory of Open Access Journals (Sweden)

    Robert A. Dielenberg

    2013-05-01

    Full Text Available The hallmark of our species is our ability to hybridize symbolic thinking with behavioral output. We began with the symmetrical hand axe around 1.7 mya and have progressed, slowly at first, then with greater rapidity, to producing increasingly more complex hybridized products. We now live in the age where our drive to hybridize has pushed us to the brink of a neuroscientific revolution, where for the first time we are in a position to willfully alter the brain and hence, our behavior and evolution. Nootropics, transcranial direct current stimulation (tDCS, transcranial magnetic stimulation (TMS, deep brain stimulation (DBS and invasive brain mind interface (BMI technology are allowing humans to treat previously inaccessible diseases as well as open up potential vistas for cognitive enhancement. In the future, the possibility exists for humans to hybridize with BMIs and mobile architectures. The notion of self is becoming increasingly extended. All of this to say: are we in control of our brains, or are they in control of us?

  1. A Novel Human Body Area Network for Brain Diseases Analysis.

    Science.gov (United States)

    Lin, Kai; Xu, Tianlang

    2016-10-01

    Development of wireless sensor and mobile communication technology provide an unprecedented opportunity for realizing smart and interactive healthcare systems. Designing such systems aims to remotely monitor the health and diagnose the diseases for users. In this paper, we design a novel human body area network for brain diseases analysis, which is named BABDA. Considering the brain is one of the most complex organs in the human body, the BABDA system provides four function modules to ensure the high quality of the analysis result, which includes initial data collection, data correction, data transmission and comprehensive data analysis. The performance evaluation conducted in a realistic environment with several criteria shows the availability and practicability of the BABDA system.

  2. Magnetic Deposits of Iron Oxides in the Human Brain

    Directory of Open Access Journals (Sweden)

    Makohusová Miroslava

    2014-06-01

    Full Text Available Deposits of iron oxides in the human brain (globus pallidus are visible under electron microscopy as object of regular and or/irregular shape but giving sharp diffraction patterns in the transmission mode. The SQUID magnetometry reveals that the magnetization curves decline form an ideal Langevin function due to the dominating diamagnetism of organic tissue. The fitting procedure yields the quantitative characteristics of the overall magnetization curves that were further processed by statistical multivariate methods

  3. Human brain arteriovenous malformations express lymphatic-associated genes

    OpenAIRE

    Shoemaker, Lorelei D.; Fuentes, Laurel F; Santiago, Shauna M; Allen, Breanna M; Cook, Douglas J.; Steinberg, Gary K.; Chang, Steven D.

    2014-01-01

    Objective Brain arteriovenous malformations (AVMs) are devastating, hemorrhage-prone, cerebrovascular lesions characterized by well-defined feeding arteries, draining vein(s) and the absence of a capillary bed. The endothelial cells (ECs) that comprise AVMs exhibit a loss of arterial and venous specification. Given the role of the transcription factor COUP-TFII in vascular development, EC specification, and pathological angiogenesis, we examined human AVM tissue to determine if COUP-FTII may ...

  4. Dynamic Network Centrality Summarizes Learning in the Human Brain

    OpenAIRE

    Mantzaris, Alexander V.; Bassett, Danielle S.; Wymbs, Nicholas F.; Estrada, Ernesto; Porter, Mason A.; Mucha, Peter J; Grafton, Scott T.; Higham, Desmond J.

    2012-01-01

    We study functional activity in the human brain using functional Magnetic Resonance Imaging and recently developed tools from network science. The data arise from the performance of a simple behavioural motor learning task. Unsupervised clustering of subjects with respect to similarity of network activity measured over three days of practice produces significant evidence of `learning', in the sense that subjects typically move between clusters (of subjects whose dynamics are similar) as time ...

  5. A mechanistic account of value computation in the human brain

    OpenAIRE

    Philiastides, Marios G.; Biele, Guido; Heekeren, Hauke R.

    2010-01-01

    To make decisions based on the value of different options, we often have to combine different sources of probabilistic evidence. For example, when shopping for strawberries on a fruit stand, one uses their color and size to infer—with some uncertainty—which strawberries taste best. Despite much progress in understanding the neural underpinnings of value-based decision making in humans, it remains unclear how the brain represents different sources of probabilistic evidence and how they are use...

  6. DIFFERENTIATING PERIMORTEM AND POSTMORTEM BURNING

    Directory of Open Access Journals (Sweden)

    Brahmaji Master

    2015-01-01

    Full Text Available One of the most challenging cases in forensic medicine is ascertaining the cause of death of burnt bodies under suspicious circumstances. The key questions that arise at the time of investigation include: 1  Was the person alive or dead prior to fire accident?  Did the victim die because of burn?  If death was not related to burns, could burns play a role in causing death?  Were the burns sustained accidentally, did the person commit suicide or was the person murdered?  Are the circumstances suggesting an attempt to conceal crime?  How was the fire started?  How was the victim identified?  In case of mass fatalities, who died first? Postmortem burning of corpses is supposed to be one of the ways to hide a crime. Differentiating the actual cause of death in burn patients is therefore important. Medical examiners usually focus on the defining the changes that occur in tissues while forensic anthropologists deal with the changes related to the bone with or without any the influence of other tissues. Under the circumstances of fire, differentiating the perimortem trauma from that of postmortem cause of bone fractures is vital in determining the cause and motive of death

  7. Investigation of G72 (DAOA expression in the human brain

    Directory of Open Access Journals (Sweden)

    Hirsch Steven

    2008-12-01

    Full Text Available Abstract Background Polymorphisms at the G72/G30 locus on chromosome 13q have been associated with schizophrenia or bipolar disorder in more than ten independent studies. Even though the genetic findings are very robust, the physiological role of the predicted G72 protein has thus far not been resolved. Initial reports suggested G72 as an activator of D-amino acid oxidase (DAO, supporting the glutamate dysfunction hypothesis of schizophrenia. However, these findings have subsequently not been reproduced and reports of endogenous human G72 mRNA and protein expression are extremely limited. In order to better understand the function of this putative schizophrenia susceptibility gene, we attempted to demonstrate G72 mRNA and protein expression in relevant human brain regions. Methods The expression of G72 mRNA was studied by northern blotting and semi-quantitative SYBR-Green and Taqman RT-PCR. Protein expression in human tissue lysates was investigated by western blotting using two custom-made specific anti-G72 peptide antibodies. An in-depth in silico analysis of the G72/G30 locus was performed in order to try and identify motifs or regulatory elements that provide insight to G72 mRNA expression and transcript stability. Results Despite using highly sensitive techniques, we failed to identify significant levels of G72 mRNA in a variety of human tissues (e.g. adult brain, amygdala, caudate nucleus, fetal brain, spinal cord and testis human cell lines or schizophrenia/control post mortem BA10 samples. Furthermore, using western blotting in combination with sensitive detection methods, we were also unable to detect G72 protein in a number of human brain regions (including cerebellum and amygdala, spinal cord or testis. A detailed in silico analysis provides several lines of evidence that support the apparent low or absent expression of G72. Conclusion Our results suggest that native G72 protein is not normally present in the tissues that we analysed

  8. Imaging synaptic density in the living human brain.

    Science.gov (United States)

    Finnema, Sjoerd J; Nabulsi, Nabeel B; Eid, Tore; Detyniecki, Kamil; Lin, Shu-Fei; Chen, Ming-Kai; Dhaher, Roni; Matuskey, David; Baum, Evan; Holden, Daniel; Spencer, Dennis D; Mercier, Joël; Hannestad, Jonas; Huang, Yiyun; Carson, Richard E

    2016-07-20

    Chemical synapses are the predominant neuron-to-neuron contact in the central nervous system. Presynaptic boutons of neurons contain hundreds of vesicles filled with neurotransmitters, the diffusible signaling chemicals. Changes in the number of synapses are associated with numerous brain disorders, including Alzheimer's disease and epilepsy. However, all current approaches for measuring synaptic density in humans require brain tissue from autopsy or surgical resection. We report the use of the synaptic vesicle glycoprotein 2A (SV2A) radioligand [(11)C]UCB-J combined with positron emission tomography (PET) to quantify synaptic density in the living human brain. Validation studies in a baboon confirmed that SV2A is an alternative synaptic density marker to synaptophysin. First-in-human PET studies demonstrated that [(11)C]UCB-J had excellent imaging properties. Finally, we confirmed that PET imaging of SV2A was sensitive to synaptic loss in patients with temporal lobe epilepsy. Thus, [(11)C]UCB-J PET imaging is a promising approach for in vivo quantification of synaptic density with several potential applications in diagnosis and therapeutic monitoring of neurological and psychiatric disorders. Copyright © 2016, American Association for the Advancement of Science.

  9. Functional interactions as big data in the human brain.

    Science.gov (United States)

    Turk-Browne, Nicholas B

    2013-11-01

    Noninvasive studies of human brain function hold great potential to unlock mysteries of the human mind. The complexity of data generated by such studies, however, has prompted various simplifying assumptions during analysis. Although this has enabled considerable progress, our current understanding is partly contingent upon these assumptions. An emerging approach embraces the complexity, accounting for the fact that neural representations are widely distributed, neural processes involve interactions between regions, interactions vary by cognitive state, and the space of interactions is massive. Because what you see depends on how you look, such unbiased approaches provide the greatest flexibility for discovery.

  10. Characterisation of new monoclonal antibodies reacting with prions from both human and animal brain tissues.

    Science.gov (United States)

    Cordes, Henriette; Bergström, Ann-Louise; Ohm, Jakob; Laursen, Henning; Heegaard, Peter M H

    2008-09-15

    Post-mortem diagnosis of transmissible spongiform encephalopathies (prion diseases) is primarily based on the detection of a protease resistant, misfolded disease associated isoform (PrP(Sc)) of the prion protein (PrP(C)) on neuronal cells. These methods depend on antibodies directed against PrP(C) and capable of reacting with PrP(Sc)in situ (immunohistochemistry on nervous tissue sections) or with the unfolded form of the protein (western and paraffin embedded tissue (PET) blotting). Here, high-affinity monoclonal antibodies (mAbs 1.5D7, 1.6F4) were produced against synthetic PrP peptides in wild-type mice and used for western blotting and immunohistochemistry to detect several types of human prion-disease associated PrP(Sc), including sporadic Creutzfeldt-Jakob Disease (CJD) (subtypes MM1 and VV2), familial CJD and Gerstmann-Sträussler-Scheinker (GSS) disease PrP(Sc) as well as PrP(Sc) of bovine spongiform encephalopathy (bovine brain), scrapie (ovine brain) and experimental scrapie in hamster and in mice. The antibodies were also used for PET-blotting in which PrP(Sc) blotted from brain tissue sections onto a nitrocellulose membrane is visualized with antibodies after protease and denaturant treatment allowing the detection of protease resistant PrP forms (PrP(RES)) in situ. Monoclonal antibodies 1.5D7 and 1.6F4 were raised against the reported epitope (PrP153-165) of the commercial antibody 6H4. While 1.5D7 and 1.6F4 were completely inhibitable by PrP153-165, 6H4 was not, indicating that the specificity of 6H4 is not defined completely by PrP153-165. The two antibodies performed similarly to 6H4 in western blotting with human samples, but showed less reactivity and enhanced background staining with animal samples in this method. In immunohistochemistry 1.5D7 and 1.6F4 performed better than 6H4 suggesting that the binding affinity of 1.5D7 and 1.6F4 with native (aggregated) PrP(Sc)in situ was higher than that of 6H4. On the other hand in PET-blotting, 6H4

  11. Studies on Colony Stimulating Factor Receptor-1 and Ligands Colony Stimulating Factor-1 and Interleukin-34 in Alzheimer's Disease Brains and Human Microglia.

    Science.gov (United States)

    Walker, Douglas G; Tang, Tiffany M; Lue, Lih-Fen

    2017-01-01

    Microglia are dependent on signaling through the colony stimulating factor-1 receptor (CSF-1R/CD115) for growth and survival. Activation of CSF-1R can lead to cell division, while blocking CSF-1R can lead to rapid microglia cell death. CSF-1R has two ligands, the growth factors colony stimulating factor-1 (CSF-1) and the more recently identified interleukin-34 (IL-34). Studies of IL-34 activation of rodent microglia and human macrophages have suggested it has different properties to CSF-1, resulting in an anti-inflammatory reparative phenotype. The goal of this study was to identify if the responses of human postmortem brain microglia to IL-34 differed from their responses to CSF-1 with the aim of identifying different phenotypes of microglia as a result of their responses. To approach this question, we also sought to identify differences between IL-34, CSF-1, and CSF-1R expression in human brain samples to establish whether there was an imbalance in Alzheimer's disease (AD). Using human brain samples [inferior temporal gyrus (ITG) and middle temporal gyrus (MTG)] from distinct cohorts of AD, control and high pathology, or mild cognitive impairment cases, we showed that there was increased expression of CSF-1R and CSF-1 mRNAs in both series of AD cases, and reduced expression of IL-34 mRNA in AD ITG samples. There was no change in expression of these genes in RNA from cerebellum of AD, Parkinson's disease (PD), or control cases. The results suggested an imbalance in CSF-1R signaling in AD. Using RNA sequencing to compare gene expression responses of CSF-1 and IL-34 stimulated human microglia, a profile of responses to CSF-1 and IL-34 was identified. Contrary to earlier work with rodent microglia, IL-34 induced primarily a classical activation response similar to that of CSF-1. It was not possible to identify any genes expressed significantly different by IL-34-stimulated microglia compared to CSF-1-stimulated microglia, but both cytokines did induce certain

  12. Studies on Colony Stimulating Factor Receptor-1 and Ligands Colony Stimulating Factor-1 and Interleukin-34 in Alzheimer's Disease Brains and Human Microglia

    Directory of Open Access Journals (Sweden)

    Douglas G. Walker

    2017-08-01

    Full Text Available Microglia are dependent on signaling through the colony stimulating factor-1 receptor (CSF-1R/CD115 for growth and survival. Activation of CSF-1R can lead to cell division, while blocking CSF-1R can lead to rapid microglia cell death. CSF-1R has two ligands, the growth factors colony stimulating factor-1 (CSF-1 and the more recently identified interleukin-34 (IL-34. Studies of IL-34 activation of rodent microglia and human macrophages have suggested it has different properties to CSF-1, resulting in an anti-inflammatory reparative phenotype. The goal of this study was to identify if the responses of human postmortem brain microglia to IL-34 differed from their responses to CSF-1 with the aim of identifying different phenotypes of microglia as a result of their responses. To approach this question, we also sought to identify differences between IL-34, CSF-1, and CSF-1R expression in human brain samples to establish whether there was an imbalance in Alzheimer's disease (AD. Using human brain samples [inferior temporal gyrus (ITG and middle temporal gyrus (MTG] from distinct cohorts of AD, control and high pathology, or mild cognitive impairment cases, we showed that there was increased expression of CSF-1R and CSF-1 mRNAs in both series of AD cases, and reduced expression of IL-34 mRNA in AD ITG samples. There was no change in expression of these genes in RNA from cerebellum of AD, Parkinson's disease (PD, or control cases. The results suggested an imbalance in CSF-1R signaling in AD. Using RNA sequencing to compare gene expression responses of CSF-1 and IL-34 stimulated human microglia, a profile of responses to CSF-1 and IL-34 was identified. Contrary to earlier work with rodent microglia, IL-34 induced primarily a classical activation response similar to that of CSF-1. It was not possible to identify any genes expressed significantly different by IL-34-stimulated microglia compared to CSF-1-stimulated microglia, but both cytokines did induce

  13. Effects of psychotropic drugs on brain plasticity in humans.

    Science.gov (United States)

    Paulzen, Michael; Veselinovic, Tanja; Gründer, Gerhard

    2014-01-01

    Although neurotransmitter-based hypotheses still prevail current thinking about the mechanism of action of psychotropic drugs, recent insight into the pathophysiology of psychiatric disorders has unveiled a range of new therapeutic actions of the drugs used to treat those disorders. Especially antidepressants seem to exert at least some of their effects via restoration of synaptic/neuronal plasticity. In addition, there is increasing evidence that several of the second-generation antipsychotics and some anticonvulsants affect neuronal survival/apoptosis as well as synaptic plasticity. Most of this evidence stems from work in animals. In this review, we will focus on the evidence for neuroplastic effects of psychotropic drugs in humans being aware of the fact that most of the data are derived from animals and that volumetric studies in humans can only indicate structural plasticity and not necessarily functional plasticity. However, as the data from human studies are rather poor and inconclusive, and sometimes even conflicting, it seems impossible to draw general conclusions. Until now studies on neuroplasticity in humans can only explain small pieces of the effects of psychotropic drugs on brain plasticity in humans. Nevertheless, future prospects for the development of new drugs targeting brain plasticity will be of importance and will complete this overview.

  14. Changes in Postmortem Identity and Grief.

    Science.gov (United States)

    Doka, Kenneth J

    2017-01-01

    This article reviews the concept of postmortem identity, noting its relationships to other concepts such as relational trauma. Identity is a very fluid concept that can change even after an individual's death as new information becomes available or even as social values change. Such modifications of postmortem identity can affect the course of bereavement-complication reactions to loss.

  15. Postmortem changes in muscle fibres autofluorescence

    OpenAIRE

    Chagnot, Caroline; Venien, Annie; Jamme, Frédéric; Refregiers, Mathieu; Astruc, Thierry

    2014-01-01

    After slaughter, the muscle cells undergo biochemical and physicochemical changes which may affect their autofluorescence characteristics. The postmortem metabolism kinetic of rat EDL and soleus muscles was assessed by glycogen depletion determination while autofluorescent response of different muscle fiber types was investigated by Deep UV synchrotron microspectroscopy at slaughter and and 24 hours postmortem. Following a 275 nm excitation, emission fluorescence...

  16. A proteomic network approach across the ALS-FTD disease spectrum resolves clinical phenotypes and genetic vulnerability in human brain.

    Science.gov (United States)

    Umoh, Mfon E; Dammer, Eric B; Dai, Jingting; Duong, Duc M; Lah, James J; Levey, Allan I; Gearing, Marla; Glass, Jonathan D; Seyfried, Nicholas T

    2018-01-01

    Amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD) are neurodegenerative diseases with overlap in clinical presentation, neuropathology, and genetic underpinnings. The molecular basis for the overlap of these disorders is not well established. We performed a comparative unbiased mass spectrometry-based proteomic analysis of frontal cortical tissues from postmortem cases clinically defined as ALS, FTD, ALS and FTD (ALS/FTD), and controls. We also included a subset of patients with the C9orf72 expansion mutation, the most common genetic cause of both ALS and FTD Our systems-level analysis of the brain proteome integrated both differential expression and co-expression approaches to assess the relationship of these differences to clinical and pathological phenotypes. Weighted co-expression network analysis revealed 15 modules of co-expressed proteins, eight of which were significantly different across the ALS-FTD disease spectrum. These included modules associated with RNA binding proteins, synaptic transmission, and inflammation with cell-type specificity that showed correlation with TDP-43 pathology and cognitive dysfunction. Modules were also examined for their overlap with TDP-43 protein-protein interactions, revealing one module enriched with RNA-binding proteins and other causal ALS genes that increased in FTD/ALS and FTD cases. A module enriched with astrocyte and microglia proteins was significantly increased in ALS cases carrying the C9orf72 mutation compared to sporadic ALS cases, suggesting that the genetic expansion is associated with inflammation in the brain even without clinical evidence of dementia. Together, these findings highlight the utility of integrative systems-level proteomic approaches to resolve clinical phenotypes and genetic mechanisms underlying the ALS-FTD disease spectrum in human brain. © 2017 The Authors. Published under the terms of the CC BY 4.0 license.

  17. MR-visible brain water content in human acute stroke

    DEFF Research Database (Denmark)

    Gideon, P; Rosenbaum, S; Sperling, B

    1999-01-01

    Quantification of metabolite concentrations by proton magnetic resonance spectroscopy (1H-MRS) in the human brain using water as an internal standard is based on the assumption that water content does not change significantly in pathologic brain tissue. To test this, we used 1H-MRS to estimate...... brain water content during the course of cerebral infarction. Measurements were performed serially in the acute, subacute, and chronic phase of infarction. Fourteen patients with acute cerebral infarction were examined as well as 9 healthy controls. To correlate with regional cerebral blood flow (r......CBF from Day 0-3 to Day 4-7 (p = 0.050) and from Day 0-3 to Day 8-21 (p = 0.028). No correlation between rCBF and water content was found. Water content in ischemic brain tissue increased significantly between Day 4-7 after stroke. This should be considered when performing quantitative 1H-MRS using water...

  18. A new microcontroller-based human brain hypothermia system.

    Science.gov (United States)

    Kapidere, Metin; Ahiska, Raşit; Güler, Inan

    2005-10-01

    Many studies show that artificial hypothermia of brain in conditions of anesthesia with the rectal temperature lowered down to 33 degrees C produces pronounced prophylactic effect protecting the brain from anoxia. Out of the methods employed now in clinical practice for reducing the oxygen consumption by the cerebral tissue, the most efficacious is craniocerebral hypothermia (CCH). It is finding even more extensive application in cardiovascular surgery, neurosurgery, neurorenimatology and many other fields of medical practice. In this study, a microcontroller-based designed human brain hypothermia system (HBHS) is designed and constructed. The system is intended for cooling and heating the brain. HBHS consists of a thermoelectric hypothermic helmet, a control and a power unit. Helmet temperature is controlled by 8-bit PIC16F877 microcontroller which is programmed using MPLAB editor. Temperature is converted to 10-bit digital and is controlled automatically by the preset values which have been already entered in the microcontroller. Calibration is controlled and the working range is tested. Temperature of helmet is controlled between -5 and +46 degrees C by microcontroller, with the accuracy of +/-0.5 degrees C.

  19. 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.

  20. Organizational Principles of Abstract Words in the Human Brain.

    Science.gov (United States)

    Wang, Xiaosha; Wu, Wei; Ling, Zhenhua; Xu, Yangwen; Fang, Yuxing; Wang, Xiaoying; Binder, Jeffrey R; Men, Weiwei; Gao, Jia-Hong; Bi, Yanchao

    2017-11-23

    words constitute nearly half of the human lexicon and are critically associated with human abstract thoughts, yet little is known about how they are represented in the brain. We tested the neural basis of 2 classical cognitive notions of abstract meaning representation: by linguistic contexts and by semantic features. We collected fMRI BOLD responses for 360 abstract words and built theoretical representational models from state-of-the-art corpus-based natural language processing models and behavioral ratings of semantic features. Representational similarity analyses revealed that both linguistic contextual and semantic feature similarity affected the representation of abstract concepts, but in distinct neural levels. The corpus-based similarity was coded in the high-level linguistic processing system, whereas semantic feature information was reflected in distributed brain regions and in the principal component space derived from whole-brain activation patterns. These findings highlight the multidimensional organization and the neural dissociation between linguistic contextual and featural aspects of abstract concepts. © The Author 2017. Published by Oxford University Press. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.

  1. Canonical Genetic Signatures of the Adult Human Brain

    Science.gov (United States)

    Hawrylycz, Michael; Miller, Jeremy A.; Menon, Vilas; Feng, David; Dolbeare, Tim; Guillozet-Bongaarts, Angela L.; Jegga, Anil G.; Aronow, Bruce J.; Lee, Chang-Kyu; Bernard, Amy; Glasser, Matthew F.; Dierker, Donna L.; Menche, Jörge; Szafer, Aaron; Collman, Forrest; Grange, Pascal; Berman, Kenneth A.; Mihalas, Stefan; Yao, Zizhen; Stewart, Lance; Barabási, Albert-László; Schulkin, Jay; Phillips, John; Ng, Lydia; Dang, Chinh; Haynor, David R.; Jones, Allan; Van Essen, David C.; Koch, Christof; Lein, Ed

    2015-01-01

    The structure and function of the human brain are highly stereotyped, implying a conserved molecular program responsible for its development, cellular structure, and function. We applied a correlation-based metric of “differential stability” (DS) to assess reproducibility of gene expression patterning across 132 structures in six individual brains, revealing meso-scale genetic organization. The highest DS genes are highly biologically relevant, with enrichment for brain-related biological annotations, disease associations, drug targets, and literature citations. Using high DS genes we identified 32 anatomically diverse and reproducible gene expression signatures, which represent distinct cell types, intracellular components, and/or associations with neurodevelopmental and neurodegenerative disorders. Genes in neuron-associated compared to non-neuronal networks showed higher preservation between human and mouse; however, many diversely-patterned genes displayed dramatic shifts in regulation between species. Finally, highly consistent transcriptional architecture in neocortex is correlated with resting state functional connectivity, suggesting a link between conserved gene expression and functionally relevant circuitry. PMID:26571460

  2. Sexual orientation and the size of the anterior commissure in the human brain.

    Science.gov (United States)

    Allen, L S; Gorski, R A

    1992-08-01

    The anterior commissure, a fiber tract that is larger in its midsagittal area in women than in men, was examined in 90 postmortem brains from homosexual men, heterosexual men, and heterosexual women. The midsagittal plane of the anterior commissure in homosexual men was 18% larger than in heterosexual women and 34% larger than in heterosexual men. This anatomical difference, which correlates with gender and sexual orientation, may, in part, underlie differences in cognitive function and cerebral lateralization among homosexual men, heterosexual men, and heterosexual women. Moreover, this finding of a difference in a structure not known to be related to reproductive functions supports the hypothesis that factors operating early in development differentiate sexually dimorphic structures and functions of the brain, including the anterior commissure and sexual orientation, in a global fashion.

  3. Toward an integrative science of the developing human mind and brain: Focus on the developing cortex☆

    Science.gov (United States)

    Jernigan, Terry L.; Brown, Timothy T.; Bartsch, Hauke; Dale, Anders M.

    2015-01-01

    Based on the Huttenlocher lecture, this article describes the need for a more integrative scientific paradigm for addressing important questions raised by key observations made over 2 decades ago. Among these are the early descriptions by Huttenlocher of variability in synaptic density in cortex of postmortem brains of children of different ages and the almost simultaneous reports of cortical volume reductions on MR imaging in children and adolescents. In spite of much progress in developmental neurobiology, developmental cognitive neuroscience, and behavioral and imaging genetics, we still do not know how these early observations relate to each other. It is argued that large scale, collaborative research programs are needed to establish the associations between behavioral differences among children and imaging biomarkers, and to link the latter to cellular changes in the developing brain. Examples of progress and challenges remaining are illustrated with data from the Pediatric Imaging, Neurocognition, and Genetics Project (PING). PMID:26347228

  4. Toward an integrative science of the developing human mind and brain: Focus on the developing cortex.

    Science.gov (United States)

    Jernigan, Terry L; Brown, Timothy T; Bartsch, Hauke; Dale, Anders M

    2016-04-01

    Based on the Huttenlocher lecture, this article describes the need for a more integrative scientific paradigm for addressing important questions raised by key observations made over 2 decades ago. Among these are the early descriptions by Huttenlocher of variability in synaptic density in cortex of postmortem brains of children of different ages and the almost simultaneous reports of cortical volume reductions on MR imaging in children and adolescents. In spite of much progress in developmental neurobiology, developmental cognitive neuroscience, and behavioral and imaging genetics, we still do not know how these early observations relate to each other. It is argued that large scale, collaborative research programs are needed to establish the associations between behavioral differences among children and imaging biomarkers, and to link the latter to cellular changes in the developing brain. Examples of progress and challenges remaining are illustrated with data from the Pediatric Imaging, Neurocognition, and Genetics Project (PING). Copyright © 2015 The Authors. Published by Elsevier Ltd.. All rights reserved.

  5. Quantitative magnetic resonance imaging and studies of degenerative diseases of the developing human brain

    Energy Technology Data Exchange (ETDEWEB)

    Caviness, V.S. Jr. (Massachusetts General Hospital, Boston, MA (United States)); Phil, D.; Filipek, P.A.; Kennedy, D.N.

    1992-05-01

    The Rett syndrome is a progressive disorder which is associated with regression of psychomotor development and precipitous deceleration of brain growth during the first year of life. General histopathological surveys in postmortem specimens have identified degeneration of subpopulations of neurons of the nigrostriatal system but no other evidence of degenerative process. Magnetic resonance imaging-based morphometry may usefully guide application of rigorous but demanding quantitative histologic search for evidence of neuronal degeneration. The volumes of the principal set of cortical and nuclear structures of principal interest in the disorder may be measured by currently avaiable MRI-based methods. Opimized levels of precision now allow detection of volumetric changes over time in the same brain of approximately 10% at the 95% confidence level. (author).

  6. Consequences of traumatic brain injury for human vergence dynamics.

    Science.gov (United States)

    Tyler, Christopher W; Likova, Lora T; Mineff, Kristyo N; Elsaid, Anas M; Nicholas, Spero C

    2014-01-01

    Traumatic brain injury involving loss of consciousness has focal effects in the human brainstem, suggesting that it may have particular consequences for eye movement control. This hypothesis was investigated by measurements of vergence eye movement parameters. Disparity vergence eye movements were measured for a population of 123 normally sighted individuals, 26 of whom had suffered diffuse traumatic brain injury (dTBI) in the past, while the remainder served as controls. Vergence tracking responses were measured to sinusoidal disparity modulation of a random-dot field. Disparity vergence step responses were characterized in terms of their dynamic parameters separately for the convergence and divergence directions. The control group showed notable differences between convergence and divergence dynamics. The dTBI group showed significantly abnormal vergence behavior on many of the dynamic parameters. The results support the hypothesis that occult injury to the oculomotor control system is a common residual outcome of dTBI.

  7. Memory-related brain lateralisation in birds and humans.

    Science.gov (United States)

    Moorman, Sanne; Nicol, Alister U

    2015-03-01

    Visual imprinting in chicks and song learning in songbirds are prominent model systems for the study of the neural mechanisms of memory. In both systems, neural lateralisation has been found to be involved in memory formation. Although many processes in the human brain are lateralised--spatial memory and musical processing involves mostly right hemisphere dominance, whilst language is mostly left hemisphere dominant--it is unclear what the function of lateralisation is. It might enhance brain capacity, make processing more efficient, or prevent occurrence of conflicting signals. In both avian paradigms we find memory-related lateralisation. We will discuss avian lateralisation findings and propose that birds provide a strong model for studying neural mechanisms of memory-related lateralisation. Copyright © 2014. Published by Elsevier Ltd.

  8. A Map for Social Navigation in the Human Brain.

    Science.gov (United States)

    Tavares, Rita Morais; Mendelsohn, Avi; Grossman, Yael; Williams, Christian Hamilton; Shapiro, Matthew; Trope, Yaacov; Schiller, Daniela

    2015-07-01

    Deciphering the neural mechanisms of social behavior has propelled the growth of social neuroscience. The exact computations of the social brain, however, remain elusive. Here we investigated how the human brain tracks ongoing changes in social relationships using functional neuroimaging. Participants were lead characters in a role-playing game in which they were to find a new home and a job through interactions with virtual cartoon characters. We found that a two-dimensional geometric model of social relationships, a "social space" framed by power and affiliation, predicted hippocampal activity. Moreover, participants who reported better social skills showed stronger covariance between hippocampal activity and "movement" through "social space." The results suggest that the hippocampus is crucial for social cognition, and imply that beyond framing physical locations, the hippocampus computes a more general, inclusive, abstract, and multidimensional cognitive map consistent with its role in episodic memory. Copyright © 2015 Elsevier Inc. All rights reserved.

  9. Supramodal representations of perceived emotions in the human brain.

    Science.gov (United States)

    Peelen, Marius V; Atkinson, Anthony P; Vuilleumier, Patrik

    2010-07-28

    Basic emotional states (such as anger, fear, and joy) can be similarly conveyed by the face, the body, and the voice. Are there human brain regions that represent these emotional mental states regardless of the sensory cues from which they are perceived? To address this question, in the present study participants evaluated the intensity of emotions perceived from face movements, body movements, or vocal intonations, while their brain activity was measured with functional magnetic resonance imaging (fMRI). Using multivoxel pattern analysis, we compared the similarity of response patterns across modalities to test for brain regions in which emotion-specific patterns in one modality (e.g., faces) could predict emotion-specific patterns in another modality (e.g., bodies). A whole-brain searchlight analysis revealed modality-independent but emotion category-specific activity patterns in medial prefrontal cortex (MPFC) and left superior temporal sulcus (STS). Multivoxel patterns in these regions contained information about the category of the perceived emotions (anger, disgust, fear, happiness, sadness) across all modality comparisons (face-body, face-voice, body-voice), and independently of the perceived intensity of the emotions. No systematic emotion-related differences were observed in the overall amplitude of activation in MPFC or STS. These results reveal supramodal representations of emotions in high-level brain areas previously implicated in affective processing, mental state attribution, and theory-of-mind. We suggest that MPFC and STS represent perceived emotions at an abstract, modality-independent level, and thus play a key role in the understanding and categorization of others' emotional mental states.

  10. The evolution of distributed association networks in the human brain.

    Science.gov (United States)

    Buckner, Randy L; Krienen, Fenna M

    2013-12-01

    The human cerebral cortex is vastly expanded relative to other primates and disproportionately occupied by distributed association regions. Here we offer a hypothesis about how association networks evolved their prominence and came to possess circuit properties vital to human cognition. The rapid expansion of the cortical mantle may have untethered large portions of the cortex from strong constraints of molecular gradients and early activity cascades that lead to sensory hierarchies. What fill the gaps between these hierarchies are densely interconnected networks that widely span the cortex and mature late into development. Limitations of the tethering hypothesis are discussed as well as its broad implications for understanding critical features of the human brain as a byproduct of size scaling. Copyright © 2013 Elsevier Ltd. All rights reserved.

  11. Social Rewards and Social Networks in the Human Brain.

    Science.gov (United States)

    Fareri, Dominic S; Delgado, Mauricio R

    2014-08-01

    The rapid development of social media and social networking sites in human society within the past decade has brought about an increased focus on the value of social relationships and being connected with others. Research suggests that we pursue socially valued or rewarding outcomes-approval, acceptance, reciprocity-as a means toward learning about others and fulfilling social needs of forming meaningful relationships. Focusing largely on recent advances in the human neuroimaging literature, we review findings highlighting the neural circuitry and processes that underlie pursuit of valued rewarding outcomes across non-social and social domains. We additionally discuss emerging human neuroimaging evidence supporting the idea that social rewards provide a gateway to establishing relationships and forming social networks. Characterizing the link between social network, brain, and behavior can potentially identify contributing factors to maladaptive influences on decision making within social situations. © The Author(s) 2014.

  12. Comparative Analysis of the Macroscale Structural Connectivity in the Macaque and Human Brain

    NARCIS (Netherlands)

    Goulas, A.; Bastiani, M.; Bezgin, G.; Uylings, H.B.M.; Roebroeck, A.; Stiers, P.

    2014-01-01

    The macaque brain serves as a model for the human brain, but its suitability is challenged by unique human features, including connectivity reconfigurations, which emerged during primate evolution. We perform a quantitative comparative analysis of the whole brain macroscale structural connectivity

  13. Infection and upregulation of proinflammatory cytokines in human brain vascular pericytes by human cytomegalovirus

    Directory of Open Access Journals (Sweden)

    Alcendor Donald J

    2012-05-01

    Full Text Available Abstract Background Congenital human cytomegalovirus (HCMV infections can result in CNS abnormalities in newborn babies including vision loss, mental retardation, motor deficits, seizures, and hearing loss. Brain pericytes play an essential role in the development and function of the blood–brain barrier yet their unique role in HCMV dissemination and neuropathlogy has not been reported. Methods Primary human brain vascular pericytes were exposed to a primary clinical isolate of HCMV designated ‘SBCMV’. Infectivity was analyzed by microscopy, immunofluorescence, Western blot, and qRT-PCR. Microarrays were performed to identify proinflammatory cytokines upregulated after SBCMV exposure, and the results validated by real-time quantitative polymerase chain reaction (qPCR methodology. In situ cytokine expression of pericytes after exposure to HCMV was examined by ELISA and in vivo evidence of HCMV infection of brain pericytes was shown by dual-labeled immunohistochemistry. Results HCMV-infected human brain vascular pericytes as evidenced by several markers. Using a clinical isolate of HCMV (SBCMV, microscopy of infected pericytes showed virion production and typical cytomegalic cytopathology. This finding was confirmed by the expression of major immediate early and late virion proteins and by the presence of HCMV mRNA. Brain pericytes were fully permissive for CMV lytic replication after 72 to 96 hours in culture compared to human astrocytes or human brain microvascular endothelial cells (BMVEC. However, temporal transcriptional expression of pp65 virion protein after SBCMV infection was lower than that seen with the HCMV Towne laboratory strain. Using RT-PCR and dual-labeled immunofluorescence, proinflammatory cytokines CXCL8/IL-8, CXCL11/ITAC, and CCL5/Rantes were upregulated in SBCMV-infected cells, as were tumor necrosis factor-alpha (TNF-alpha, interleukin-1 beta (IL-1beta, and interleukin-6 (IL-6. Pericytes exposed to SBCMV elicited

  14. Infection and upregulation of proinflammatory cytokines in human brain vascular pericytes by human cytomegalovirus

    Science.gov (United States)

    2012-01-01

    Background Congenital human cytomegalovirus (HCMV) infections can result in CNS abnormalities in newborn babies including vision loss, mental retardation, motor deficits, seizures, and hearing loss. Brain pericytes play an essential role in the development and function of the blood–brain barrier yet their unique role in HCMV dissemination and neuropathlogy has not been reported. Methods Primary human brain vascular pericytes were exposed to a primary clinical isolate of HCMV designated ‘SBCMV’. Infectivity was analyzed by microscopy, immunofluorescence, Western blot, and qRT-PCR. Microarrays were performed to identify proinflammatory cytokines upregulated after SBCMV exposure, and the results validated by real-time quantitative polymerase chain reaction (qPCR) methodology. In situ cytokine expression of pericytes after exposure to HCMV was examined by ELISA and in vivo evidence of HCMV infection of brain pericytes was shown by dual-labeled immunohistochemistry. Results HCMV-infected human brain vascular pericytes as evidenced by several markers. Using a clinical isolate of HCMV (SBCMV), microscopy of infected pericytes showed virion production and typical cytomegalic cytopathology. This finding was confirmed by the expression of major immediate early and late virion proteins and by the presence of HCMV mRNA. Brain pericytes were fully permissive for CMV lytic replication after 72 to 96 hours in culture compared to human astrocytes or human brain microvascular endothelial cells (BMVEC). However, temporal transcriptional expression of pp65 virion protein after SBCMV infection was lower than that seen with the HCMV Towne laboratory strain. Using RT-PCR and dual-labeled immunofluorescence, proinflammatory cytokines CXCL8/IL-8, CXCL11/ITAC, and CCL5/Rantes were upregulated in SBCMV-infected cells, as were tumor necrosis factor-alpha (TNF-alpha), interleukin-1 beta (IL-1beta), and interleukin-6 (IL-6). Pericytes exposed to SBCMV elicited higher levels of IL-6

  15. Forensic Identification of Decomposed Human Body through Comparison between Ante-Mortem and Post-Mortem CT Images of Frontal Sinuses: Case Report

    Directory of Open Access Journals (Sweden)

    Rhonan Ferreira Silva

    2017-01-01

    Full Text Available Objective: The aim of this paper is to report on a case of positive human identification of a decomposed body after the comparison of ante-mortem (AM and port-mortem (PM computed tomography images of frontal sinus. Case report: An unknown, highly decomposed human body, aged between 30 and 40 years, was found in a forest region in Brazil. The dental autopsy revealed several teeth missing AM and the presence of removable partial prostheses. The search for AM data resulted in a sequence of 20 axial images of the paranasal sinuses obtained by Multislice Computed Tomography (MSCT. PM reproduction of the MSCT images was performed in order to enable a comparative identification. After a direct confrontation between AM/PM MSCT, the data were collected for morphological findings, specifically for the lateral expansion of the left lobe, the anteroposterior dimension, and the position of median and accessory septa of the sinuses. Conclusion: The importance of storing and interpreting radiographic medical data properly is highlighted in this text, thus pointing out the importance of application of forensic radiology in the field of law.

  16. Forensic Identification of Decomposed Human Body through Comparison between Ante-Mortem and Post-Mortem CT Images of Frontal Sinuses: Case Report

    Science.gov (United States)

    Picoli, Fernando Fortes; Botelho, Tessa de Lucena; Resende, Roberta Gomes; Franco, Ademir

    2017-01-01

    Objective The aim of this paper is to report on a case of positive human identification of a decomposed body after the comparison of ante-mortem (AM) and port-mortem (PM) computed tomography images of frontal sinus. Case report An unknown, highly decomposed human body, aged between 30 and 40 years, was found in a forest region in Brazil. The dental autopsy revealed several teeth missing AM and the presence of removable partial prostheses. The search for AM data resulted in a sequence of 20 axial images of the paranasal sinuses obtained by Multislice Computed Tomography (MSCT). PM reproduction of the MSCT images was performed in order to enable a comparative identification. After a direct confrontation between AM/PM MSCT, the data were collected for morphological findings, specifically for the lateral expansion of the left lobe, the anteroposterior dimension, and the position of median and accessory septa of the sinuses. Conclusion The importance of storing and interpreting radiographic medical data properly is highlighted in this text, thus pointing out the importance of application of forensic radiology in the field of law. PMID:29225363

  17. Multi-dimensional dynamics of human electromagnetic brain activity

    Directory of Open Access Journals (Sweden)

    Tetsuo eKida

    2016-01-01

    Full Text Available Magnetoencephalography (MEG and electroencephalography (EEG are invaluable neuroscientific tools for unveiling human neural dynamics in three dimensions (space, time, and frequency, which are associated with a wide variety of perceptions, cognition, and actions. MEG/EEG also provides different categories of neuronal indices including activity magnitude, connectivity, and network properties along the three dimensions. In the last 20 years, interest has increased in inter-regional connectivity and complex network properties assessed by various sophisticated scientific analyses. We herein review the definition, computation, short history, and pros and cons of connectivity and complex network (graph-theory analyses applied to MEG/EEG signals. We briefly describe recent developments in source reconstruction algorithms essential for source-space connectivity and network analyses. Furthermore, we discuss a relatively novel approach used in MEG/EEG studies to examine the complex dynamics represented by human brain activity. The correct and effective use of these neuronal metrics provides a new insight into the multi-dimensional dynamics of the neural representations of various functions in the complex human brain.

  18. Multi-Dimensional Dynamics of Human Electromagnetic Brain Activity.

    Science.gov (United States)

    Kida, Tetsuo; Tanaka, Emi; Kakigi, Ryusuke

    2015-01-01

    Magnetoencephalography (MEG) and electroencephalography (EEG) are invaluable neuroscientific tools for unveiling human neural dynamics in three dimensions (space, time, and frequency), which are associated with a wide variety of perceptions, cognition, and actions. MEG/EEG also provides different categories of neuronal indices including activity magnitude, connectivity, and network properties along the three dimensions. In the last 20 years, interest has increased in inter-regional connectivity and complex network properties assessed by various sophisticated scientific analyses. We herein review the definition, computation, short history, and pros and cons of connectivity and complex network (graph-theory) analyses applied to MEG/EEG signals. We briefly describe recent developments in source reconstruction algorithms essential for source-space connectivity and network analyses. Furthermore, we discuss a relatively novel approach used in MEG/EEG studies to examine the complex dynamics represented by human brain activity. The correct and effective use of these neuronal metrics provides a new insight into the multi-dimensional dynamics of the neural representations of various functions in the complex human brain.

  19. Why our brains cherish humanity: Mirror neurons and colamus humanitatem

    Directory of Open Access Journals (Sweden)

    John R. Skoyles

    2008-06-01

    Full Text Available Commonsense says we are isolated. After all, our bodies are physically separate. But Seneca’s colamus humanitatem, and John Donne’s observation that “no man is an island” suggests we are neither entirely isolated nor separate. A recent discovery in neuroscience—that of mirror neurons—argues that the brain and the mind is neither built nor functions remote from what happens in other individuals. What are mirror neurons? They are brain cells that process both what happens to or is done by an individual, and, as it were, its perceived “refl ection,” when that same thing happens or is done by another individual. Thus, mirror neurons are both activated when an individual does a particular action, and when that individual perceives that same action done by another. The discovery of mirror neurons suggests we need to radically revise our notions of human nature since they offer a means by which we may not be so separated as we think. Humans unlike other apes are adapted to mirror interact nonverbally when together. Notably, our faces have been evolved to display agile and nimble movements. While this is usually explained as enabling nonverbal communication, a better description would be nonverbal commune based upon mirror neurons. I argue we cherish humanity, colamus humanitatem, because mirror neurons and our adapted mirror interpersonal interface blur the physical boundaries that separate us.

  20. Studying variability in human brain aging in a population-based German cohort—rationale and design of 1000BRAINS

    OpenAIRE

    Svenja eCaspers; Susanne eMoebus; Silke eLux; Noreen ePundt; Holger eSchütz; Mühleisen, Thomas W.; Vincent eGras; Eickhoff, Simon B.; Sandro eRomanzetti; Tony eStöcker; Rüdiger eStirnberg; Kirlangic, Mehmet E.; Martina eMinnerop; Peter ePieperhoff; Ulrich eMödder

    2014-01-01

    The ongoing 1000 brains study (1000BRAINS) is an epidemiological and neuroscientific investigation of structural and functional variability in the human brain during aging. The two recruitment sources are the 10-year follow-up cohort of the German Heinz Nixdorf Recall (HNR) Study, and the HNR MultiGeneration Study cohort, which comprises spouses and offspring of HNR subjects. The HNR is a longitudinal epidemiological investigation of cardiovascular risk factors, with a comprehensive collectio...

  1. Accelerated evolution of the ASPM gene controlling brain size begins prior to human brain expansion.

    Directory of Open Access Journals (Sweden)

    Natalay Kouprina

    2004-05-01

    Full Text Available Primary microcephaly (MCPH is a neurodevelopmental disorder characterized by global reduction in cerebral cortical volume. The microcephalic brain has a volume comparable to that of early hominids, raising the possibility that some MCPH genes may have been evolutionary targets in the expansion of the cerebral cortex in mammals and especially primates. Mutations in ASPM, which encodes the human homologue of a fly protein essential for spindle function, are the most common known cause of MCPH. Here we have isolated large genomic clones containing the complete ASPM gene, including promoter regions and introns, from chimpanzee, gorilla, orangutan, and rhesus macaque by transformation-associated recombination cloning in yeast. We have sequenced these clones and show that whereas much of the sequence of ASPM is substantially conserved among primates, specific segments are subject to high Ka/Ks ratios (nonsynonymous/synonymous DNA changes consistent with strong positive selection for evolutionary change. The ASPM gene sequence shows accelerated evolution in the African hominoid clade, and this precedes hominid brain expansion by several million years. Gorilla and human lineages show particularly accelerated evolution in the IQ domain of ASPM. Moreover, ASPM regions under positive selection in primates are also the most highly diverged regions between primates and nonprimate mammals. We report the first direct application of TAR cloning technology to the study of human evolution. Our data suggest that evolutionary selection of specific segments of the ASPM sequence strongly relates to differences in cerebral cortical size.

  2. Accelerated evolution of the ASPM gene controlling brain size begins prior to human brain expansion.

    Science.gov (United States)

    Kouprina, Natalay; Pavlicek, Adam; Mochida, Ganeshwaran H; Solomon, Gregory; Gersch, William; Yoon, Young-Ho; Collura, Randall; Ruvolo, Maryellen; Barrett, J Carl; Woods, C Geoffrey; Walsh, Christopher A; Jurka, Jerzy; Larionov, Vladimir

    2004-05-01

    Primary microcephaly (MCPH) is a neurodevelopmental disorder characterized by global reduction in cerebral cortical volume. The microcephalic brain has a volume comparable to that of early hominids, raising the possibility that some MCPH genes may have been evolutionary targets in the expansion of the cerebral cortex in mammals and especially primates. Mutations in ASPM, which encodes the human homologue of a fly protein essential for spindle function, are the most common known cause of MCPH. Here we have isolated large genomic clones containing the complete ASPM gene, including promoter regions and introns, from chimpanzee, gorilla, orangutan, and rhesus macaque by transformation-associated recombination cloning in yeast. We have sequenced these clones and show that whereas much of the sequence of ASPM is substantially conserved among primates, specific segments are subject to high Ka/Ks ratios (nonsynonymous/synonymous DNA changes) consistent with strong positive selection for evolutionary change. The ASPM gene sequence shows accelerated evolution in the African hominoid clade, and this precedes hominid brain expansion by several million years. Gorilla and human lineages show particularly accelerated evolution in the IQ domain of ASPM. Moreover, ASPM regions under positive selection in primates are also the most highly diverged regions between primates and nonprimate mammals. We report the first direct application of TAR cloning technology to the study of human evolution. Our data suggest that evolutionary selection of specific segments of the ASPM sequence strongly relates to differences in cerebral cortical size.

  3. Evaluation of molecular brain changes associated with environmental stress in rodent models compared to human major depressive disorder: A proteomic systems approach.

    Science.gov (United States)

    Cox, David Alan; Gottschalk, Michael Gerd; Stelzhammer, Viktoria; Wesseling, Hendrik; Cooper, Jason David; Bahn, Sabine

    2016-11-25

    Rodent models of major depressive disorder (MDD) are indispensable when screening for novel treatments, but assessing their translational relevance with human brain pathology has proved difficult. Using a novel systems approach, proteomics data obtained from post-mortem MDD anterior prefrontal cortex tissue (n = 12) and matched controls (n = 23) were compared with equivalent data from three commonly used preclinical models exposed to environmental stressors (chronic mild stress, prenatal stress and social defeat). Functional pathophysiological features associated with depression-like behaviour were identified in these models through enrichment of protein-protein interaction networks. A cross-species comparison evaluated which model(s) represent human MDD pathology most closely. Seven functional domains associated with MDD and represented across at least two models such as "carbohydrate metabolism and cellular respiration" were identified. Through statistical evaluation using kernel-based machine learning techniques, the social defeat model was found to represent MDD brain changes most closely for four of the seven domains. This is the first study to apply a method for directly evaluating the relevance of the molecular pathology of multiple animal models to human MDD on the functional level. The methodology and findings outlined here could help to overcome translational obstacles of preclinical psychiatric research.

  4. Alcohol's Effects on the Brain: Neuroimaging Results in Humans and Animal Models

    National Research Council Canada - National Science Library

    Natalie M Zahr; Adolf Pfefferbaum

    2017-01-01

    ... into the effects of chronic alcoholism on the human brain. Magnetic resonance imaging (MRI) studies have distinguished alcohol-related brain effects that are permanent from those that are reversible with abstinence...

  5. Postmortem cardiac imaging in fetuses and children

    Energy Technology Data Exchange (ETDEWEB)

    Taylor, Andrew M. [Great Ormond Street Hospital for Children NHS Foundation Trust, Cardiorespiratory Division, Level 7, Old Nurses Home, London (United Kingdom); UCL Institute of Cardiovascular Science, London (United Kingdom); Arthurs, Owen J. [Great Ormond Street Hospital for Children NHS Foundation Trust, Department of Radiology, London (United Kingdom); UCL Institute of Cardiovascular Science, London (United Kingdom); Sebire, Neil J. [UCL Institute of Cardiovascular Science, London (United Kingdom); Great Ormond Street Hospital for Children NHS Foundation Trust, Department of Histopathology, London (United Kingdom)

    2015-04-01

    Fetal and pediatric cardiac autopsies have a crucial role in the counseling of parents with regard to both the cause of death of their child and the implications of such findings for future pregnancies, as well as for quality assurance of antenatal screening programs and antemortem diagnostic procedures. Postmortem imaging allows an opportunity to investigate the heart in situ prior to dissection, and both postmortem CT and postmortem MRI have shown excellent accuracy in detecting the majority of clinically significant cardiac lesions in the perinatal and pediatric population. As less-invasive autopsy becomes increasingly popular, clinical guidelines for maximal diagnostic yield in specific circumstances can be developed. (orig.)

  6. The representation of biological classes in the human brain.

    Science.gov (United States)

    Connolly, Andrew C; Guntupalli, J Swaroop; Gors, Jason; Hanke, Michael; Halchenko, Yaroslav O; Wu, Yu-Chien; Abdi, Hervé; Haxby, James V

    2012-02-22

    Evidence of category specificity from neuroimaging in the human visual system is generally limited to a few relatively coarse categorical distinctions-e.g., faces versus bodies, or animals versus artifacts-leaving unknown the neural underpinnings of fine-grained category structure within these large domains. Here we use fMRI to explore brain activity for a set of categories within the animate domain, including six animal species-two each from three very different biological classes: primates, birds, and insects. Patterns of activity throughout ventral object vision cortex reflected the biological classes of the stimuli. Specifically, the abstract representational space-measured as dissimilarity matrices defined between species-specific multivariate patterns of brain activity-correlated strongly with behavioral judgments of biological similarity of the same stimuli. This biological class structure was uncorrelated with structure measured in retinotopic visual cortex, which correlated instead with a dissimilarity matrix defined by a model of V1 cortex for the same stimuli. Additionally, analysis of the shape of the similarity space in ventral regions provides evidence for a continuum in the abstract representational space-with primates at one end and insects at the other. Further investigation into the cortical topography of activity that contributes to this category structure reveals the partial engagement of brain systems active normally for inanimate objects in addition to animate regions.

  7. MR-visible brain water content in human acute stroke

    DEFF Research Database (Denmark)

    Gideon, P; Rosenbaum, S; Sperling, B

    1999-01-01

    CBF) SPECT-scanning using 99mTc-HMPAO as flow tracer was performed in the patients. Mean water content (SD) in the infarct area was 37.7 (5.1); 41.8 (4.8); 35.2 (5.4); and 39.3 (5.1) mol x [kg wet weight](-1) at 0-3; 4-7; 8-21; and >180 days after stroke, respectively. Water content increased between Day 0......Quantification of metabolite concentrations by proton magnetic resonance spectroscopy (1H-MRS) in the human brain using water as an internal standard is based on the assumption that water content does not change significantly in pathologic brain tissue. To test this, we used 1H-MRS to estimate...... brain water content during the course of cerebral infarction. Measurements were performed serially in the acute, subacute, and chronic phase of infarction. Fourteen patients with acute cerebral infarction were examined as well as 9 healthy controls. To correlate with regional cerebral blood flow (r...

  8. Mobile phone types and SAR characteristics of the human brain

    Science.gov (United States)

    Lee, Ae-Kyoung; Hong, Seon-Eui; Kwon, Jong-Hwa; Choi, Hyung-Do; Cardis, Elisabeth

    2017-04-01

    Mobile phones differ in terms of their operating frequency, outer shape, and form and location of the antennae, all of which affect the spatial distributions of their electromagnetic field and the level of electromagnetic absorption in the human head or brain. For this paper, the specific absorption rate (SAR) was calculated for four anatomical head models at different ages using 11 numerical phone models of different shapes and antenna configurations. The 11 models represent phone types accounting for around 86% of the approximately 1400 commercial phone models released into the Korean market since 2002. Seven of the phone models selected have an internal dual-band antenna, and the remaining four possess an external antenna. Each model was intended to generate an average absorption level equivalent to that of the same type of commercial phone model operating at the maximum available output power. The 1 g peak spatial SAR and ipsilateral and contralateral brain-averaged SARs were reported for all 11 phone models. The effects of the phone type, phone position, operating frequency, and age of head models on the brain SAR were comprehensively determined.

  9. Unmasking Language Lateralization in Human Brain Intrinsic Activity.

    Science.gov (United States)

    McAvoy, Mark; Mitra, Anish; Coalson, Rebecca S; d'Avossa, Giovanni; Keidel, James L; Petersen, Steven E; Raichle, Marcus E

    2016-04-01

    Lateralization of function is a fundamental feature of the human brain as exemplified by the left hemisphere dominance of language. Despite the prominence of lateralization in the lesion, split-brain and task-based fMRI literature, surprisingly little asymmetry has been revealed in the increasingly popular functional imaging studies of spontaneous fluctuations in the fMRI BOLD signal (so-called resting-state fMRI). Here, we show the global signal, an often discarded component of the BOLD signal in resting-state studies, reveals a leftward asymmetry that maps onto regions preferential for semantic processing in left frontal and temporal cortex and the right cerebellum and a rightward asymmetry that maps onto putative attention-related regions in right frontal, temporoparietal, and parietal cortex. Hemispheric asymmetries in the global signal resulted from amplitude modulation of the spontaneous fluctuations. To confirm these findings obtained from normal, healthy, right-handed subjects in the resting-state, we had them perform 2 semantic processing tasks: synonym and numerical magnitude judgment and sentence comprehension. In addition to establishing a new technique for studying lateralization through functional imaging of the resting-state, our findings shed new light on the physiology of the global brain signal. © The Author 2015. Published by Oxford University Press. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.

  10. Hard x-ray micro-tomography of a human head post-mortem as a gold standard to compare x-ray modalities

    Science.gov (United States)

    Dalstra, M.; Schulz, G.; Dagassan-Berndt, D.; Verna, C.; Müller-Gerbl, M.; Müller, B.

    2016-10-01

    An entire human head obtained at autopsy was micro-CT scanned in a nano/micro-CT scanner in a 6-hour long session. Despite the size of the head, it could still be scanned with a pixel size of 70 μm. The aim of this study was to obtain an optimal quality 3D data-set to be used as baseline control in a larger study comparing the image quality of various cone beam CT systems currently used in dentistry. The image quality of the micro-CT scans was indeed better than the ones of the clinical imaging modalities, both with regard to noise and streak artifacts due to metal dental implants. Bony features in the jaws, like the trabecular architecture and the thin wall of the alveolar bone were clearly visible. Therefore, the 3D micro-CT data-set can be used as the gold standard for linear, angular, and volumetric measurements of anatomical features in and around the oral cavity when comparing clinical imaging modalities.

  11. Stable functional networks exhibit consistent timing in the human brain.

    Science.gov (United States)

    Chapeton, Julio I; Inati, Sara K; Zaghloul, Kareem A

    2017-03-01

    Despite many advances in the study of large-scale human functional networks, the question of timing, stability, and direction of communication between cortical regions has not been fully addressed. At the cellular level, neuronal communication occurs through axons and dendrites, and the time required for such communication is well defined and preserved. At larger spatial scales, however, the relationship between timing, direction, and communication between brain regions is less clear. Here, we use a measure of effective connectivity to identify connections between brain regions that exhibit communication with consistent timing. We hypothesized that if two brain regions are communicating, then knowledge of the activity in one region should allow an external observer to better predict activity in the other region, and that such communication involves a consistent time delay. We examine this question using intracranial electroencephalography captured from nine human participants with medically refractory epilepsy. We use a coupling measure based on time-lagged mutual information to identify effective connections between brain regions that exhibit a statistically significant increase in average mutual information at a consistent time delay. These identified connections result in sparse, directed functional networks that are stable over minutes, hours, and days. Notably, the time delays associated with these connections are also highly preserved over multiple time scales. We characterize the anatomic locations of these connections, and find that the propagation of activity exhibits a preferred posterior to anterior temporal lobe direction, consistent across participants. Moreover, networks constructed from connections that reliably exhibit consistent timing between anatomic regions demonstrate features of a small-world architecture, with many reliable connections between anatomically neighbouring regions and few long range connections. Together, our results demonstrate

  12. The brain's silent messenger: using selective attention to decode human thought for brain-based communication.

    Science.gov (United States)

    Naci, Lorina; Cusack, Rhodri; Jia, Vivian Z; Owen, Adrian M

    2013-05-29

    The interpretation of human thought from brain activity, without recourse to speech or action, is one of the most provoking and challenging frontiers of modern neuroscience. In particular, patients who are fully conscious and awake, yet, due to brain damage, are unable to show any behavioral responsivity, expose the limits of the neuromuscular system and the necessity for alternate forms of communication. Although it is well established that selective attention can significantly enhance the neural representation of attended sounds, it remains, thus far, untested as a response modality for brain-based communication. We asked whether its effect could be reliably used to decode answers to binary (yes/no) questions. Fifteen healthy volunteers answered questions (e.g., "Do you have brothers or sisters?") in the fMRI scanner, by selectively attending to the appropriate word ("yes" or "no"). Ninety percent of the answers were decoded correctly based on activity changes within the attention network. The majority of volunteers conveyed their answers with less than 3 min of scanning, suggesting that this technique is suited for communication in a reasonable amount of time. Formal comparison with the current best-established fMRI technique for binary communication revealed improved individual success rates and scanning times required to detect responses. This novel fMRI technique is intuitive, easy to use in untrained participants, and reliably robust within brief scanning times. Possible applications include communication with behaviorally nonresponsive patients.

  13. Telomere length modulation in human astroglial brain tumors.

    Directory of Open Access Journals (Sweden)

    Domenico La Torre

    Full Text Available BACKGROUND: Telomeres alteration during carcinogenesis and tumor progression has been described in several cancer types. Telomeres length is stabilized by telomerase (h-TERT and controlled by several proteins that protect telomere integrity, such as the Telomere Repeat-binding Factor (TRF 1 and 2 and the tankyrase-poli-ADP-ribose polymerase (TANKs-PARP complex. OBJECTIVE: To investigate telomere dysfunction in astroglial brain tumors we analyzed telomeres length, telomerase activity and the expression of a panel of genes controlling the length and structure of telomeres in tissue samples obtained in vivo from astroglial brain tumors with different grade of malignancy. MATERIALS AND METHODS: Eight Low Grade Astrocytomas (LGA, 11 Anaplastic Astrocytomas (AA and 11 Glioblastoma Multiforme (GBM samples were analyzed. Three samples of normal brain tissue (NBT were used as controls. Telomeres length was assessed through Southern Blotting. Telomerase activity was evaluated by a telomere repeat amplification protocol (TRAP assay. The expression levels of TRF1, TRF2, h-TERT and TANKs-PARP complex were determined through Immunoblotting and RT-PCR. RESULTS: LGA were featured by an up-regulation of TRF1 and 2 and by shorter telomeres. Conversely, AA and GBM were featured by a down-regulation of TRF1 and 2 and an up-regulation of both telomerase and TANKs-PARP complex. CONCLUSIONS: In human astroglial brain tumours, up-regulation of TRF1 and TRF2 occurs in the early stages of carcinogenesis determining telomeres shortening and genomic instability. In a later stage, up-regulation of PARP-TANKs and telomerase activation may occur together with an ADP-ribosylation of TRF1, causing a reduced ability to bind telomeric DNA, telomeres elongation and tumor malignant progression.

  14. Selectively altering belief formation in the human brain.

    Science.gov (United States)

    Sharot, Tali; Kanai, Ryota; Marston, David; Korn, Christoph W; Rees, Geraint; Dolan, Raymond J

    2012-10-16

    Humans form beliefs asymmetrically; we tend to discount bad news but embrace good news. This reduced impact of unfavorable information on belief updating may have important societal implications, including the generation of financial market bubbles, ill preparedness in the face of natural disasters, and overly aggressive medical decisions. Here, we selectively improved people's tendency to incorporate bad news into their beliefs by disrupting the function of the left (but not right) inferior frontal gyrus using transcranial magnetic stimulation, thereby eliminating the engrained "good news/bad news effect." Our results provide an instance of how selective disruption of regional human brain function paradoxically enhances the ability to incorporate unfavorable information into beliefs of vulnerability.

  15. Generation of iPSC-derived Human Brain Organoids to Model Early Neurodevelopmental Disorders.

    Science.gov (United States)

    Gabriel, Elke; Gopalakrishnan, Jay

    2017-04-14

    The restricted availability of suitable in vitro models that can reliably represent complex human brain development is a significant bottleneck that limits the translation of basic brain research into clinical application. While induced pluripotent stem cells (iPSCs) have replaced the ethically questionable human embryonic stem cells, iPSC-based neuronal differentiation studies remain descriptive at the cellular level but fail to adequately provide the details that could be derived from a complex, 3D human brain tissue. This gap is now filled through the application of iPSC-derived, 3D brain organoids, "Brains in a dish," that model many features of complex human brain development. Here, a method for generating iPSC-derived, 3D brain organoids is described. The organoids can help with modeling autosomal recessive primary microcephaly (MCPH), a rare human neurodevelopmental disorder. A widely accepted explanation for the brain malformation in MCPH is a depletion of the neural stem cell pool during the early stages of human brain development, a developmental defect that is difficult to recreate or prove in vitro. To study MCPH, we generated iPSCs from patient-derived fibroblasts carrying a mutation in the centrosomal protein CPAP. By analyzing the ventricular zone of microcephaly 3D brain organoids, we showed the premature differentiation of neural progenitors. These 3D brain organoids are a powerful in vitro system that will be instrumental in modeling congenital brain disorders induced by neurotoxic chemicals, neurotrophic viral infections, or inherited genetic mutations.

  16. Three cortical stages of colour processing in the human brain.

    Science.gov (United States)

    Zeki, S; Marini, L

    1998-09-01

    We used the technique of functional magnetic resonance imaging to chart the colour pathways in the human brain beyond V4. We asked subjects to view objects that were dressed in natural and unnatural colours as well as their achromatic counterparts and compared the activity produced in the brain by each condition. The results showed that both naturally and unnaturally coloured objects activate a pathway extending from V1 to V4, though not overlapping totally the activity produced by viewing abstract coloured Mondrian scenes. Normally coloured objects activated, in addition, more anterior parts of the fusiform gyrus, the hippocampus and the ventrolateral frontal cortex. Abnormally coloured objects, by contrast, activated the dorsolateral frontal cortex. A study of the cortical covariation produced by these activations revealed that activity in large parts of the occipital lobe covaried with each. These results, considered against the background of previous physiological and clinical studies, allow us to discern three broad cortical stages of colour processing in the human brain. The first is based on V1 and possibly V2 and is concerned mainly with registering the presence and intensity of different wavelengths, and with wavelength differencing. The second stage is based on V4 and is concerned with automatic colour constancy operations, without regard to memory, judgement and learning. The third stage, based on the inferior temporal and frontal cortex, is more concerned with object colours. The results we report, as well as the schema that we suggest, also allow us to reconcile the computational theory of Land, implemented without regard to cognitive factors such as memory and learning, and the cognitive systems of Helmholtz and Hering, which view such factors as critical in the determination of colours.

  17. Sexual dimorphism of the human brain: myth and reality.

    Science.gov (United States)

    Hofman, M A; Swaab, D F

    1991-01-01

    Many neuroanatomical sex differences have been identified in both animals and humans, which may form the neural bases for sex-specific behavior and reproductive as well as non-reproductive functions. The present essay gives a brief review of the findings on sex differences in the human brain. Our observations on the human hypothalamus revealed that the shape of the suprachiasmatic nucleus (SCN)--a structure involved in the regulation of circadian rhythms and reproductive cycles--is elongated in females and more spherical in males. In addition, an extremely large SCN was observed in the brains of homosexual men who died from AIDS. Both the volume of the SCN and the number of vasopressin neurons were about twice as large as in a male reference group. In contrast to the SCN, in which only shape differences were found in relation to gender, the volume and cell number of the sexually dimorphic nucleus of the preoptic area (SDN-POA) showed a marked sexual dimorphism. The mean volume of the SDN-POA was 2.2 times larger in males than in females and contained about twice as many cells. The function of this sexually dimorphic area in humans is not known, but presumably it is involved in the control of male sexual behavior. The fact that no differences in either volume or cell number were observed between the SDN-POAs of homo- and heterosexual men indicates a selectivity of the SCN in this respect and contradicts the view that male homosexuals have a 'female' hypothalamus.

  18. Hypnosis and imaging of the living human brain.

    Science.gov (United States)

    Landry, Mathieu; Raz, Amir

    2015-01-01

    Over more than two decades, studies using imaging techniques of the living human brain have begun to explore the neural correlates of hypnosis. The collective findings provide a gripping, albeit preliminary, account of the underlying neurobiological mechanisms involved in hypnotic phenomena. While substantial advances lend support to different hypotheses pertaining to hypnotic modulation of attention, control, and monitoring processes, the complex interactions among the many mediating variables largely hinder our ability to isolate robust commonalities across studies. The present account presents a critical integrative synthesis of neuroimaging studies targeting hypnosis as a function of suggestion. Specifically, hypnotic induction without task-specific suggestion is examined, as well as suggestions concerning sensation and perception, memory, and ideomotor response. The importance of carefully designed experiments is highlighted to better tease apart the neural correlates that subserve hypnotic phenomena. Moreover, converging findings intimate that hypnotic suggestions seem to induce specific neural patterns. These observations propose that suggestions may have the ability to target focal brain networks. Drawing on evidence spanning several technological modalities, neuroimaging studies of hypnosis pave the road to a more scientific understanding of a dramatic, yet largely evasive, domain of human behavior.

  19. Language representation in the human brain: evidence from cortical mapping.

    Science.gov (United States)

    Bhatnagar, S C; Mandybur, G T; Buckingham, H W; Andy, O J

    2000-09-01

    The manner in which the human brain processes grammatical-syntactic and lexical-semantic functions has been extensively debated in neurolinguistics. The discreteness and selectivity of the representation of syntactic-morphological properties in the dominant frontal cortex and the representation of the lexical-semantics in the temporo-parietal cortex have been questioned. Three right-handed adult male neurosurgical patients undergoing left craniotomy for intractable seizures were evaluated using various grammatical and semantic tasks during cortical mapping. The sampling of language tasks consisted of trials with stimulation (experimental) and without stimulation (control) from sites in the dominant fronto-temporo-parietal cortex The sampling of language implicated a larger cortical area devoted to language (syntactic-morphological and lexical-semantic) tasks. Further, a large part of the fronto-parieto-temporal cortex was involved with syntactic-morphological functions. However, only the parieto-temporal sites were implicated with the ordering of lexicon in sentence construction. These observations suggest that the representation of language in the human brain may be columnar or multilayered. Copyright 2000 Academic Press.

  20. Flow distributions and spatial correlations in human brain capillary networks

    Science.gov (United States)

    Lorthois, Sylvie; Peyrounette, Myriam; Larue, Anne; Le Borgne, Tanguy

    2015-11-01

    The vascular system of the human brain cortex is composed of a space filling mesh-like capillary network connected upstream and downstream to branched quasi-fractal arterioles and venules. The distribution of blood flow rates in these networks may affect the efficiency of oxygen transfer processes. Here, we investigate the distribution and correlation properties of blood flow velocities from numerical simulations in large 3D human intra-cortical vascular network (10000 segments) obtained from an anatomical database. In each segment, flow is solved from a 1D non-linear model taking account of the complex rheological properties of blood flow in microcirculation to deduce blood pressure, blood flow and red blood cell volume fraction distributions throughout the network. The network structural complexity is found to impart broad and spatially correlated Lagrangian velocity distributions, leading to power law transit time distributions. The origins of this behavior (existence of velocity correlations in capillary networks, influence of the coupling with the feeding arterioles and draining veins, topological disorder, complex blood rheology) are studied by comparison with results obtained in various model capillary networks of controlled disorder. ERC BrainMicroFlow GA615102, ERC ReactiveFronts GA648377.

  1. Gaze-and-brain-controlled interfaces for human-computer and human-robot interaction

    Directory of Open Access Journals (Sweden)

    Shishkin S. L.

    2017-09-01

    Full Text Available Background. Human-machine interaction technology has greatly evolved during the last decades, but manual and speech modalities remain single output channels with their typical constraints imposed by the motor system’s information transfer limits. Will brain-computer interfaces (BCIs and gaze-based control be able to convey human commands or even intentions to machines in the near future? We provide an overview of basic approaches in this new area of applied cognitive research. Objective. We test the hypothesis that the use of communication paradigms and a combination of eye tracking with unobtrusive forms of registering brain activity can improve human-machine interaction. Methods and Results. Three groups of ongoing experiments at the Kurchatov Institute are reported. First, we discuss the communicative nature of human-robot interaction, and approaches to building a more e cient technology. Specifically, “communicative” patterns of interaction can be based on joint attention paradigms from developmental psychology, including a mutual “eye-to-eye” exchange of looks between human and robot. Further, we provide an example of “eye mouse” superiority over the computer mouse, here in emulating the task of selecting a moving robot from a swarm. Finally, we demonstrate a passive, noninvasive BCI that uses EEG correlates of expectation. This may become an important lter to separate intentional gaze dwells from non-intentional ones. Conclusion. The current noninvasive BCIs are not well suited for human-robot interaction, and their performance, when they are employed by healthy users, is critically dependent on the impact of the gaze on selection of spatial locations. The new approaches discussed show a high potential for creating alternative output pathways for the human brain. When support from passive BCIs becomes mature, the hybrid technology of the eye-brain-computer (EBCI interface will have a chance to enable natural, fluent, and the

  2. Gaze-and-brain-controlled interfaces for human-computer and human-robot interaction.

    Directory of Open Access Journals (Sweden)

    Shishkin S. L.

    2017-10-01

    Full Text Available Background. Human-machine interaction technology has greatly evolved during the last decades, but manual and speech modalities remain single output channels with their typical constraints imposed by the motor system’s information transfer limits. Will brain-computer interfaces (BCIs and gaze-based control be able to convey human commands or even intentions to machines in the near future? We provide an overview of basic approaches in this new area of applied cognitive research. Objective. We test the hypothesis that the use of communication paradigms and a combination of eye tracking with unobtrusive forms of registering brain activity can improve human-machine interaction. Methods and Results. Three groups of ongoing experiments at the Kurchatov Institute are reported. First, we discuss the communicative nature of human-robot interaction, and approaches to building a more e cient technology. Specifically, “communicative” patterns of interaction can be based on joint attention paradigms from developmental psychology, including a mutual “eye-to-eye” exchange of looks between human and robot. Further, we provide an example of “eye mouse” superiority over the computer mouse, here in emulating the task of selecting a moving robot from a swarm. Finally, we demonstrate a passive, noninvasive BCI that uses EEG correlates of expectation. This may become an important lter to separate intentional gaze dwells from non-intentional ones. Conclusion. The current noninvasive BCIs are not well suited for human-robot interaction, and their performance, when they are employed by healthy users, is critically dependent on the impact of the gaze on selection of spatial locations. The new approaches discussed show a high potential for creating alternative output pathways for the human brain. When support from passive BCIs becomes mature, the hybrid technology of the eye-brain-computer (EBCI interface will have a chance to enable natural, fluent, and the

  3. The Formation of Ethanol in Postmortem Tissues

    National Research Council Canada - National Science Library

    Johnson, Robert

    2004-01-01

    .... During toxicological evaluations, ethanol analysis is performed on all cases. Many species of bacteria, yeast and fungi have the ability to produce ethanol and other volatile organic compounds in postmortem specimens...

  4. Human Development XII: A Theory for the Structure and Function of the Human Brain

    Directory of Open Access Journals (Sweden)

    Søren Ventegodt

    2008-01-01

    Full Text Available The human brain is probably the most complicated single structure in the biological universe. The cerebral cortex that is traditionally connected with consciousness is extremely complex. The brain contains approximately 1,000,000 km of nerve fibers, indicating its enormous complexity and which makes it difficult for scientists to reveal the function of the brain. In this paper, we propose a new model for brain functions, i.e., information-guided self-organization of neural patterns, where information is provided from the abstract wholeness of the biophysical system of an organism (often called the true self, or the “soul””. We present a number of arguments in favor of this model that provide self-conscious control over the thought process or cognition. Our arguments arise from analyzing experimental data from different research fields: histology, anatomy, electroencephalography (EEG, cerebral blood flow, neuropsychology, evolutionary studies, and mathematics. We criticize the popular network theories as the consequence of a simplistic, mechanical interpretation of reality (philosophical materialism applied to the brain. We demonstrate how viewing brain functions as information-guided self-organization of neural patterns can explain the structure of conscious mentation; we seem to have a dual hierarchical representation in the cerebral cortex: one for sensation-perception and one for will-action. The model explains many of our unique mental abilities to think, memorize, associate, discriminate, and make abstractions. The presented model of the conscious brain also seems to be able to explain the function of the simpler brains, such as those of insects and hydra.

  5. A digital interactive human brain atlas based on Chinese visible human datasets for anatomy teaching.

    Science.gov (United States)

    Li, Qiyu; Ran, Xu; Zhang, Shaoxiang; Tan, Liwen; Qiu, Mingguo

    2014-01-01

    As we know, the human brain is one of the most complicated organs in the human body, which is the key and difficult point in neuroanatomy and sectional anatomy teaching. With the rapid development and extensive application of imaging technology in clinical diagnosis, doctors are facing higher and higher requirement on their anatomy knowledge. Thus, to cultivate medical students to meet the needs of medical development today and to improve their ability to read and understand radiographic images have become urgent challenges for the medical teachers. In this context, we developed a digital interactive human brain atlas based on the Chinese visible human datasets for anatomy teaching (available for free download from http://www.chinesevisiblehuman.com/down/DHBA.rar). The atlas simultaneously provides views in all 3 primary planes of section. The main structures of the human brain have been anatomically labeled in all 3 views. It is potentially useful for anatomy browsing, user self-testing, and automatic student assessment. In a word, it is interactive, 3D, user friendly, and free of charge, which can provide a new, intuitive means for anatomy teaching.

  6. Evolution of human brain functions: the functional structure of human consciousness.

    Science.gov (United States)

    Cloninger, C Robert

    2009-11-01

    The functional structure of self-aware consciousness in human beings is described based on the evolution of human brain functions. Prior work on heritable temperament and character traits is extended to account for the quantum-like and holographic properties (i.e. parts elicit wholes) of self-aware consciousness. Cladistic analysis is used to identify the succession of ancestors leading to human beings. The functional capacities that emerge along this lineage of ancestors are described. The ecological context in which each cladogenesis occurred is described to illustrate the shifting balance of evolution as a complex adaptive system. Comparative neuroanatomy is reviewed to identify the brain structures and networks that emerged coincident with the emergent brain functions. Individual differences in human temperament traits were well developed in the common ancestor shared by reptiles and humans. Neocortical development in mammals proceeded in five major transitions: from early reptiles to early mammals, early primates, simians, early Homo, and modern Homo sapiens. These transitions provide the foundation for human self-awareness related to sexuality, materiality, emotionality, intellectuality, and spirituality, respectively. The functional structure of human self-aware consciousness is concerned with the regulation of five planes of being: sexuality, materiality, emotionality, intellectuality, and spirituality. Each plane elaborates neocortical functions organized around one of the five special senses. The interactions among these five planes gives rise to a 5 x 5 matrix of subplanes, which are functions that coarsely describe the focus of neocortical regulation. Each of these 25 neocortical functions regulates each of five basic motives or drives that can be measured as temperaments or basic emotions related to fear, anger, disgust, surprise, and happiness/sadness. The resulting 5 x 5 x 5 matrix of human characteristics provides a general and testable model of the

  7. Reconsolidation of human memory: brain mechanisms and clinical relevance.

    Science.gov (United States)

    Schwabe, Lars; Nader, Karim; Pruessner, Jens C

    2014-08-15

    The processes of memory formation and storage are complex and highly dynamic. Once memories are consolidated, they are not necessarily fixed but can be changed long after storage. In particular, seemingly stable memories may re-enter an unstable state when they are retrieved, from which they must be re-stabilized during a process known as reconsolidation. During reconsolidation, memories are susceptible to modifications again, thus providing an opportunity to update seemingly stable memories. While initial demonstrations of memory reconsolidation came mainly from animal studies, evidence for reconsolidation in humans is now accumulating as well. Here, we review recent advances in our understanding of human memory reconsolidation. After a summary of findings on the reconsolidation of human fear and episodic memory, we focus particularly on recent neuroimaging data that provide first insights into how reconsolidation processes are implemented in the human brain. Finally, we discuss the implications of memory modifications during reconsolidation for the treatment of mental disorders such as posttraumatic stress disorder and drug addiction. Copyright © 2014 Society of Biological Psychiatry. Published by Elsevier Inc. All rights reserved.

  8. [Postmortem imaging procedures : Experiences and perspectives].

    Science.gov (United States)

    von Stillfried, S; Isfort, P; Knüchel-Clarke, R

    2017-08-21

    Autopsies are of key importance for the understanding of the anatomy, pathophysiology and pathomorphology. In forensic medicine, the virtual autopsy is a standard instrument in autopsy practice. The advantage of postmortem imaging is the generation of a three-dimensional pre-autopsy snapshot of the body from head to toe with excellent visualization of skeletal pathologies and air inclusions. When angiography is performed, pathologies of the cardiovascular system can additionally be evaluated. The shortcomings of postmortem imaging are the low soft tissue contrast with CT imaging, the lack of haptic, olfactory and color impressions. Another limitation is the access to CT and particularly to magnetic resonance imaging (MRI) facilities and the necessary experience with the peculiarities of postmortem imaging. To date, postmortem imaging can supplement but not replace the traditional autopsy. Nevertheless, postmortem imaging adds valuable technical capabilities to the traditional autopsy. The ability to achieve valid results for the cause of death and additional diagnoses must be evaluated systematically for postmortem imaging, in particular in addition to CT or MR guided biopsies. This article gives an overview of the current state of the technology and encourages its development for application in pathology departments.

  9. [Post-mortem organ donation].

    Science.gov (United States)

    Goroll, T; Gerresheim, G; Schaffartzik, W; Schwemmer, U

    2015-07-01

    In Germany approximately 3000 body organs are transplanted annually. In general, all artificially ventilated patients with diagnosed brain death are potential organ donors. All German hospitals are obliged to report potential organ donors and be actively involved in the organ donation process. These matters lie under the jurisdiction of the German transplantation act. An essential prerequisite for organ donation is the diagnosis of brain death according to the guidelines of the German Medical Association. Brain death is associated with complex pathophysiological changes in cardiopulmonary function as well as fluid, electrolyte and metabolic homeostasis. In the case of diagnosed brain death and with permission for organ donation, a precise organ-protective therapy is initiated, essentially focussing on optimal organ perfusion and oxygenation. The quality of organ protection has a direct influence on the outcome of transplantation.

  10. Human brain arteriovenous malformations express lymphatic-associated genes.

    Science.gov (United States)

    Shoemaker, Lorelei D; Fuentes, Laurel F; Santiago, Shauna M; Allen, Breanna M; Cook, Douglas J; Steinberg, Gary K; Chang, Steven D

    2014-12-01

    Brain arteriovenous malformations (AVMs) are devastating, hemorrhage-prone, cerebrovascular lesions characterized by well-defined feeding arteries, draining vein(s) and the absence of a capillary bed. The endothelial cells (ECs) that comprise AVMs exhibit a loss of arterial and venous specification. Given the role of the transcription factor COUP-TFII in vascular development, EC specification, and pathological angiogenesis, we examined human AVM tissue to determine if COUP-FTII may have a role in AVM disease biology. We examined 40 human brain AVMs by immunohistochemistry (IHC) and qRT-PCR for the expression of COUP-TFII as well as other genes involved in venous and lymphatic development, maintenance, and signaling. We also examined proliferation and EC tube formation with human umbilical ECs (HUVEC) following COUP-TFII overexpression. We report that AVMs expressed COUP-TFII, SOX18, PROX1, NFATC1, FOXC2, TBX1, LYVE1, Podoplanin, and vascular endothelial growth factor (VEGF)-C, contained Ki67-positive cells and heterogeneously expressed genes involved in Hedgehog, Notch, Wnt, and VEGF signaling pathways. Overexpression of COUP-TFII alone in vitro resulted in increased EC proliferation and dilated tubes in an EC tube formation assay in HUVEC. This suggests AVM ECs are further losing their arterial/venous specificity and acquiring a partial lymphatic molecular phenotype. There was significant correlation of gene expression with presence of clinical edema and acute hemorrhage. While the precise role of these genes in the formation, stabilization, growth and risk of hemorrhage of AVMs remains unclear, these findings have potentially important implications for patient management and treatment choice, and opens new avenues for future work on AVM disease mechanisms.

  11. Quantitative clinical proteomic study of autopsied human infarcted brain specimens to elucidate the deregulated pathways in ischemic stroke pathology.

    Science.gov (United States)

    Datta, Arnab; Akatsu, Hiroyasu; Heese, Klaus; Sze, Siu Kwan

    2013-10-08

    Ischemic stroke, still lacking an effective neuroprotective therapy is the third leading cause of global mortality and morbidity. Here, we have applied an 8-plex iTRAQ-based 2D-LC-MS/MS strategy to study the commonly regulated infarct proteome from three different brain regions (putamen, thalamus and the parietal lobe) of female Japanese patients. Infarcts were compared with age-, post-mortem interval- and location-matched control specimens. The iTRAQ experiment confidently identified 1520 proteins with 0.1% false discovery rate. Bioinformatics data mining and immunochemical validation of pivotal perturbed proteins revealed a global failure of the cellular energy metabolism in the infarcted tissues as seen by the parallel down-regulation of proteins related to glycolysis, pyruvate dehydrogenase complex, TCA cycle and oxidative phosphorylation. The concomitant down-regulation of all participating proteins (SLC25A11, SLC25A12, GOT2 and MDH2) of malate-aspartate shuttle might be responsible for the metabolic in-coordination between the cytosol and mitochondria resulting in the failure of energy metabolism. The levels of proteins related to reactive gliosis (VIM, GFAP) and anti-inflammatory response (ANXA1, ANXA2) showed an increasing trend. The elevation of ferritin (FTL, FTH1) may indicate an iron-mediated oxidative imbalance aggravating the mitochondrial failure and neurotoxicity. The deregulated proteins could be useful as potential therapeutic targets or biomarkers for ischemic stroke. Clinical proteomics of stroke has been lagging behind other areas of clinical proteomics like Alzheimer's disease or schizophrenia. Our study is the first quantitative clinical proteomics study where iTRAQ-2D-LC-MS/MS has been utilized in the area of ischemic stroke to obtain a comparative profile of human ischemic infarcts and age-, sex-, location- and post-mortem interval-matched control brain specimens. Different pathological attributes of ischemic stroke well-known through basic

  12. Brain Imaging of Human Sexual Response : Recent Developments and Future Directions

    NARCIS (Netherlands)

    Ruesink, Gerben B; Georgiadis, Janniko R

    2017-01-01

    Purpose of Review: The purpose of this study is to provide a comprehensive summary of the latest developments in the experimental brain study of human sexuality, focusing on brain connectivity during the sexual response. Recent Findings: Stable patterns of brain activation have been established for

  13. Human subcortical brain asymmetries in 15,847 people worldwide reveal effects of age and sex

    NARCIS (Netherlands)

    Guadalupe, Tulio; Mathias, Samuel R.; Vanerp, Theo G. M.; Whelan, Christopher D.; Zwiers, Marcel P.; Abe, Yoshinari; Abramovic, Lucija; Agartz, Ingrid; Andreassen, Ole A.; Arias-Vasquez, Alejandro; Aribisala, Benjamin S.; Armstrong, Nicola J.; Arolt, Volker; Artiges, Eric; Ayesa-Arriola, Rosa; Baboyan, Vatche G.; Banaschewski, Tobias; Barker, Gareth; Bastin, Mark E.; Baune, Bernhard T.; Blangero, John; Bokde, Arun L. . W.; Boedhoe, Premika S. . W.; Bose, Anushree; Brem, Silvia; Brodaty, Henry; Bromberg, Uli; Brooks, Samantha; Buechel, Christian; Buitelaar, Jan; Calhoun, Vince D.; Cannon, Dara M.; Cattrell, Anna; Cheng, Yuqi; Conrod, Patricia J.; Conzelmann, Annette; Corvin, Aiden; Crespo-Facorro, Benedicto; Crivello, Fabrice; Dannlowski, Udo; De Zubicaray, Greig I.; De Zwarte, Sonja M. C.; Deary, Ian J.; Desrivieres, Sylvane; Doan, Nhat Trung; Donohoe, Gary; Dorum, Erlend S.; Ehrlich, Stefan; Espeseth, Thomas; Fernandez, Guillen; Flor, Herta; Fouche, Jean-Paul; Frouin, Vincent; Fukunaga, Masaki; Gallinat, Jurgen; Garavan, Hugh; Gill, Michael; Suarez, Andrea Gonzalez; Gowland, Penny; Grabe, Hans J.; Grotegerd, Dominik; Gruber, Oliver; Hagenaars, Saskia; Hashimoto, Ryota; Hauser, Tobias U.; Heinz, Andreas; Hibar, Derrek P.; Hoekstra, Pieter J.; Hoogman, Martine; Howells, Fleur M.; Hu, Hao; Pol, Hilleke E. Hulshoff; Huyser, Chaim; Ittermann, Bernd; Jahanshad, Neda; Jonsson, Erik G.; Jurk, Sarah; Kahn, Rene S.; Kelly, Sinead; Kraemer, Bernd; Kugel, Harald; Kwon, Jun Soo; Lemaitre, Herve; Lesch, Klaus-Peter; Lochner, Christine; Luciano, Michelle; Marquand, Andre F.; Martin, Nicholas G.; Martinez-Zalacain, Ignacio; Martinot, Jean-Luc; Mataix-Cols, David; Mather, Karen; McDonald, Colm; McMahon, Katie L.; Medland, Sarah E.; Menchon, Jose M.; Morris, Derek W.; Mothersill, Omar; Maniega, Susana Munoz; Mwangi, Benson; Nakamae, Takashi; Nakao, Tomohiro; Narayanaswaamy, Janardhanan C.; Nees, Frauke; Nordvik, Jan E.; Onnink, A. Marten H.; Opel, Nils; Ophoff, Roel; Martinot, Marie-Laure Paillere; Orfanos, Dimitri Papadopoulos; Pauli, Paul; Paus, Tomas; Poustka, Luise; Reddy, Janardhan Y. C.; Renteria, Miguel E.; Roiz-Santianez, Roberto; Roos, Annerine; Royle, Natalie A.; Sachdev, Perminder; Sanchez-Juan, Pascual; Schmaal, Lianne; Schumann, Gunter; Shumskaya, Elena; Smolka, Michael N.; Soares, Jair C.; Soriano-Mas, Carles; Stein, Dan J.; Strike, Lachlan T.; Toro, Roberto; Turner, Jessica A.; Tzourio-Mazoyer, Nathalie; Uhlmann, Anne; Hernandez, Maria Valdes; Van den Heuvel, Odile A.; Van der Meer, Dennis; Van Haren, Neeltje E. M.; Veltman, Dick J.; Venkatasubramanian, Ganesan; Vetter, Nora C.; Vuletic, Daniella; Walitza, Susanne; Walter, Henrik; Walton, Esther; Wang, Zhen; Wardlaw, Joanna; Wen, Wei; Westlye, Lars T.; Whelan, Robert; Wittfeld, Katharina; Wolfers, Thomas; Wright, Margaret J.; Xu, Jian; Xu, Xiufeng; Yun, Je-Yeon; Zhao, JingJing; Franke, Barbara; Thompson, Paul M.; Glahn, David C.; Mazoyer, Bernard; Fisher, Simon E.; Francks, Clyde

    2017-01-01

    The two hemispheres of the human brain differ functionally and structurally. Despite over a century of research, the extent to which brain asymmetry is influenced by sex, handedness, age, and genetic factors is still controversial. Here we present the largest ever analysis of subcortical brain

  14. Autoradiographic analysis of tritiated imipramine binding in the human brain post mortem: effects of suicide

    Energy Technology Data Exchange (ETDEWEB)

    Gross-Isseroff, R.; Israeli, M.; Biegon, A.

    1989-03-01

    In vitro quantitative autoradiography of high-affinity tritiated imipramine binding sites was performed on brains of 12 suicide victims and 12 matched controls. Region-specific differences in imipramine binding were found between the two groups. Thus, the pyramidal and molecular layers of the cornu ammoni hippocampal fields and the hilus of the dentate gyrus exhibited 80%, 60%, and 90% increases in binding in the suicide group, respectively. The postcentral cortical gyrus, insular cortex, and claustrum had 45%, 28%, and 75% decreases in binding in the suicide group, respectively. No difference in imipramine binding was observed in prefrontal cortical regions, in the basal ganglia, and in mesencephalic nuclei. No sex and postmortem delay effects on imipramine binding were found. Imipramine binding was positively correlated with age, the effect of age being most pronounced in portions of the basal ganglia and temporal cortex.

  15. Localization of brain activation by umami taste in humans.

    Science.gov (United States)

    Nakamura, Yuko; Goto, Tazuko K; Tokumori, Kenji; Yoshiura, Takashi; Kobayashi, Koji; Nakamura, Yasuhiko; Honda, Hiroshi; Ninomiya, Yuzo; Yoshiura, Kazunori

    2011-08-11

    There are no credible data to support the notion that individual taste qualities have dedicated pathways leading from the tongue to the end of the pathway in the brain. Moreover, the insular cortex is activated not only by taste but also by non-taste information from oral stimuli. These responses are invariably excitatory, and it is difficult to determine whether they are sensory, motor, or proprioceptive in origin. Furthermore, umami is a more unfamiliar and complex taste than other basic tastes. Considering these issues, it may be effective to minimize somatosensory stimuli, oral movement, and psychological effects in a neuroimaging study to elicit cerebral activity by pure umami on the human tongue. For this purpose, we developed an original taste delivery system for functional magnetic resonance imaging (fMRI) studies for umami. Then, we compared the results produced by two authorized models, namely, the block design model and event-related design model, to decide the appropriate model for detecting activation by umami. Activation by the umami taste was well localized in the insular cortex using our new system and block design model analysis. The peaks of the activated areas in the middle insular cortex by umami were very close to another prototypical taste quality (salty). Although we have to carefully interpret the perceiving intensities and brain activations by taste from different sessions, this study design might be effective for detecting the accession area in the cortex of pure umami taste on the tongue. Copyright © 2011 Elsevier B.V. All rights reserved.

  16. Consequences of Traumatic Brain Injury for Human Vergence Dynamics

    Directory of Open Access Journals (Sweden)

    Christopher W Tyler

    2015-02-01

    Full Text Available Purpose: Traumatic brain injury involving loss of consciousness has focal effects in the human brainstem, suggesting that it may have particular consequences for eye movement control. This hypothesis was investigated by measurements of vergence eye movement parameters.Methods: Disparity vergence eye movements were measured for a population of 123 normally-sighted individuals, 26 of whom had suffered diffuse traumatic brain injury (dTBI in the past, while the remainder served as controls. Vergence tracking responses were measured to sinusoidal disparity modulation of a random-dot field. Disparity vergence step responses were characterized in terms of their dynamic parameters separately for the convergence and divergence directions.Results: The control group showed notable differences between convergence and divergence dynamics. The dTBI group showed significantly abnormal vergence behavior on many of the dynamic parameters.Conclusions: The support the hypothesis that occult injury to the oculomotor control system is a common residual outcome of dTBI.

  17. Motor Skill Acquisition Promotes Human Brain Myelin Plasticity

    Directory of Open Access Journals (Sweden)

    Bimal Lakhani

    2016-01-01

    Full Text Available Experience-dependent structural changes are widely evident in gray matter. Using diffusion weighted imaging (DWI, the neuroplastic effect of motor training on white matter in the brain has been demonstrated. However, in humans it is not known whether specific features of white matter relate to motor skill acquisition or if these structural changes are associated to functional network connectivity. Myelin can be objectively quantified in vivo and used to index specific experience-dependent change. In the current study, seventeen healthy young adults completed ten sessions of visuomotor skill training (10,000 total movements using the right arm. Multicomponent relaxation imaging was performed before and after training. Significant increases in myelin water fraction, a quantitative measure of myelin, were observed in task dependent brain regions (left intraparietal sulcus [IPS] and left parieto-occipital sulcus. In addition, the rate of motor skill acquisition and overall change in myelin water fraction in the left IPS were negatively related, suggesting that a slower rate of learning resulted in greater neuroplastic change. This study provides the first evidence for experience-dependent changes in myelin that are associated with changes in skilled movements in healthy young adults.

  18. The functional connectivity landscape of the human brain.

    Directory of Open Access Journals (Sweden)

    Bratislav Mišić

    Full Text Available Functional brain networks emerge and dissipate over a primarily static anatomical foundation. The dynamic basis of these networks is inter-regional communication involving local and distal regions. It is assumed that inter-regional distances play a pivotal role in modulating network dynamics. Using three different neuroimaging modalities, 6 datasets were evaluated to determine whether experimental manipulations asymmetrically affect functional relationships based on the distance between brain regions in human participants. Contrary to previous assumptions, here we show that short- and long-range connections are equally likely to strengthen or weaken in response to task demands. Additionally, connections between homotopic areas are the most stable and less likely to change compared to any other type of connection. Our results point to a functional connectivity landscape characterized by fluid transitions between local specialization and global integration. This ability to mediate functional properties irrespective of spatial distance may engender a diverse repertoire of cognitive processes when faced with a dynamic environment.

  19. Human brain activity with near-infrared spectroscopy

    Science.gov (United States)

    Luo, Qingming; Chance, Britton

    1999-09-01

    Human brain activity was studied with a real time functional Near-InfraRed Imager (fNIRI). The imager has 16 measurement channels and covers 4 cm by 9 cm detection area. Brain activities in occipital, motor and prefrontal area were studied with the fNIRI. In prefrontal stimulation, language cognition, analogies, forming memory for new associations, emotional thinking, and mental arithmetic were carried out. Experimental results measured with fNIRI are demonstrated in this paper. It was shown that fNIRI technique is able to reveal the occipital activity during visual stimulation, and co-register well with results of fMRI in the motor cortex activity during finger tapping. In the studies of the effects of left prefrontal lobe on forming memory for new associations, it is shown that left prefrontal lobe activated more under deep conditions than that under shallow encoding, especially the dorsal part. In the studies of emotional thinking, it was shown that the responses were different between positive- negative emotional thinking and negative-positive emotional thinking. In mental arithmetic studies, higher activation was found in the first task than in the second, regardless of the difficulty, and higher activation was measured in subtraction of 17 than in subtraction of 3.

  20. Frequency-based similarity detection of structures in human brain

    Science.gov (United States)

    Sims, Dave I.; Siadat, Mohammad-Reza

    2017-03-01

    Advancements in 3D scanning and volumetric imaging methods have motivated researchers to tackle new challenges related to storing, retrieving and comparing 3D models, especially in medical domain. Comparing natural rigid shapes and detecting subtle changes in 3D models of brain structures is of great importance. Precision in capturing surface details and insensitivity to shape orientation are highly desirable properties of good shape descriptors. In this paper, we propose a new method, Spherical Harmonics Distance (SHD), which leverages the power of spherical harmonics to provide more accurate representation of surface details. At the same time, the proposed method incorporates the features of a shape distribution method (D2) and inherits its insensitivity to shape orientation. Comparing SHD to a spherical harmonics based method (SPHARM) shows that the performance of the proposed method is less sensitive to rotation. Also, comparing SHD to D2 shows that the proposed method is more accurate in detecting subtle changes. The performance of the proposed method is verified by calculating the Fisher measure (FM) of extracted feature vectors. The FM of the vectors generated by SHD on average shows 27 times higher values than that of D2. Our preliminary results show that SHD successfully combines desired features from two different methods and paves the way towards better detection of subtle dissimilarities among natural rigid shapes (e.g. structures of interest in human brain). Detecting these subtle changes can be instrumental in more accurate diagnosis, prognosis and treatment planning.

  1. Online social network size is reflected in human brain structure.

    Science.gov (United States)

    Kanai, R; Bahrami, B; Roylance, R; Rees, G

    2012-04-07

    The increasing ubiquity of web-based social networking services is a striking feature of modern human society. The degree to which individuals participate in these networks varies substantially for reasons that are unclear. Here, we show a biological basis for such variability by demonstrating that quantitative variation in the number of friends an individual declares on a web-based social networking service reliably predicted grey matter density in the right superior temporal sulcus, left middle temporal gyrus and entorhinal cortex. Such regions have been previously implicated in social perception and associative memory, respectively. We further show that variability in the size of such online friendship networks was significantly correlated with the size of more intimate real-world social groups. However, the brain regions we identified were specifically associated with online social network size, whereas the grey matter density of the amygdala was correlated both with online and real-world social network sizes. Taken together, our findings demonstrate that the size of an individual's online social network is closely linked to focal brain structure implicated in social cognition.

  2. The brain's functional network architecture reveals human motives.

    Science.gov (United States)

    Hein, Grit; Morishima, Yosuke; Leiberg, Susanne; Sul, Sunhae; Fehr, Ernst

    2016-03-04

    Goal-directed human behaviors are driven by motives. Motives are, however, purely mental constructs that are not directly observable. Here, we show that the brain's functional network architecture captures information that predicts different motives behind the same altruistic act with high accuracy. In contrast, mere activity in these regions contains no information about motives. Empathy-based altruism is primarily characterized by a positive connectivity from the anterior cingulate cortex (ACC) to the anterior insula (AI), whereas reciprocity-based altruism additionally invokes strong positive connectivity from the AI to the ACC and even stronger positive connectivity from the AI to the ventral striatum. Moreover, predominantly selfish individuals show distinct functional architectures compared to altruists, and they only increase altruistic behavior in response to empathy inductions, but not reciprocity inductions. Copyright © 2016, American Association for the Advancement of Science.

  3. Cell Death-Associated Ribosomal RNA Cleavage in Postmortem Tissues and Its Forensic Applications.

    Science.gov (United States)

    Kim, Ji Yeon; Kim, Yunmi; Cha, Hyo Kyeong; Lim, Hye Young; Kim, Hyungsub; Chung, Sooyoung; Hwang, Juck-Joon; Park, Seong Hwan; Son, Gi Hoon

    2017-06-30

    Estimation of postmortem interval (PMI) is a key issue in the field of forensic pathology. With the availability of quantitative analysis of RNA levels in postmortem tissues, several studies have assessed the postmortem degradation of constitutively expressed RNA species to estimate PMI. However, conventional RNA quantification as well as biochemical and physiological changes employed thus far have limitations related to standardization or normalization. The present study focuses on an interesting feature of the subdomains of certain RNA species, in which they are site-specifically cleaved during apoptotic cell death. We found that the D8 divergent domain of ribosomal RNA (rRNA) bearing cell death-related cleavage sites was rapidly removed during postmortem RNA degradation. In contrast to the fragile domain, the 5' terminal region of 28S rRNA was remarkably stable during the postmortem period. Importantly, the differences in the degradation rates between the two domains in mammalian 28S rRNA were highly proportional to increasing PMI with a significant linear correlation observed in mice as well as human autopsy tissues. In conclusion, we demonstrate that comparison of the degradation rates between domains of a single RNA species provides quantitative information on postmortem degradation states, which can be applied for the estimation of PMI.

  4. Human Brain Activity Related to the Tactile Perception of Stickiness

    Science.gov (United States)

    Yeon, Jiwon; Kim, Junsuk; Ryu, Jaekyun; Park, Jang-Yeon; Chung, Soon-Cheol; Kim, Sung-Phil

    2017-01-01

    While the perception of stickiness serves as one of the fundamental dimensions for tactile sensation, little has been elucidated about the stickiness sensation and its neural correlates. The present study investigated how the human brain responds to perceived tactile sticky stimuli using functional magnetic resonance imaging (fMRI). To evoke tactile perception of stickiness with multiple intensities, we generated silicone stimuli with varying catalyst ratios. Also, an acrylic sham stimulus was prepared to present a condition with no sticky sensation. From the two psychophysics experiments–the methods of constant stimuli and the magnitude estimation—we could classify the silicone stimuli into two groups according to whether a sticky perception was evoked: the Supra-threshold group that evoked sticky perception and the Infra-threshold group that did not. In the Supra-threshold vs. Sham contrast analysis of the fMRI data using the general linear model (GLM), the contralateral primary somatosensory area (S1) and ipsilateral dorsolateral prefrontal cortex (DLPFC) showed significant activations in subjects, whereas no significant result was found in the Infra-threshold vs. Sham contrast. This result indicates that the perception of stickiness not only activates the somatosensory cortex, but also possibly induces higher cognitive processes. Also, the Supra- vs. Infra-threshold contrast analysis revealed significant activations in several subcortical regions, including the pallidum, putamen, caudate and thalamus, as well as in another region spanning the insula and temporal cortices. These brain regions, previously known to be related to tactile discrimination, may subserve the discrimination of different intensities of tactile stickiness. The present study unveils the human neural correlates of the tactile perception of stickiness and may contribute to broadening the understanding of neural mechanisms associated with tactile perception. PMID:28163677

  5. A collaborative brain-computer interface for improving human performance.

    Directory of Open Access Journals (Sweden)

    Yijun Wang

    Full Text Available Electroencephalogram (EEG based brain-computer interfaces (BCI have been studied since the 1970s. Currently, the main focus of BCI research lies on the clinical use, which aims to provide a new communication channel to patients with motor disabilities to improve their quality of life. However, the BCI technology can also be used to improve human performance for normal healthy users. Although this application has been proposed for a long time, little progress has been made in real-world practices due to technical limits of EEG. To overcome the bottleneck of low single-user BCI performance, this study proposes a collaborative paradigm to improve overall BCI performance by integrating information from multiple users. To test the feasibility of a collaborative BCI, this study quantitatively compares the classification accuracies of collaborative and single-user BCI applied to the EEG data collected from 20 subjects in a movement-planning experiment. This study also explores three different methods for fusing and analyzing EEG data from multiple subjects: (1 Event-related potentials (ERP averaging, (2 Feature concatenating, and (3 Voting. In a demonstration system using the Voting method, the classification accuracy of predicting movement directions (reaching left vs. reaching right was enhanced substantially from 66% to 80%, 88%, 93%, and 95% as the numbers of subjects increased from 1 to 5, 10, 15, and 20, respectively. Furthermore, the decision of reaching direction could be made around 100-250 ms earlier than the subject's actual motor response by decoding the ERP activities arising mainly from the posterior parietal cortex (PPC, which are related to the processing of visuomotor transmission. Taken together, these results suggest that a collaborative BCI can effectively fuse brain activities of a group of people to improve the overall performance of natural human behavior.

  6. Gorilla and Orangutan Brains Conform to the Primate Cellular Scaling Rules: Implications for Human Evolution

    Science.gov (United States)

    Herculano-Houzel, Suzana; Kaas, Jon H.

    2011-01-01

    Gorillas and orangutans are primates at least as large as humans, but their brains amount to about one third of the size of the human brain. This discrepancy has been used as evidence that the human brain is about 3 times larger than it should be for a primate species of its body size. In contrast to the view that the human brain is special in its size, we have suggested that it is the great apes that might have evolved bodies that are unusually large, on the basis of our recent finding that the cellular composition of the human brain matches that expected for a primate brain of its size, making the human brain a linearly scaled-up primate brain in its number of cells. To investigate whether the brain of great apes also conforms to the primate cellular scaling rules identified previously, we determine the numbers of neuronal and other cells that compose the orangutan and gorilla cerebella, use these numbers to calculate the size of the brain and of the cerebral cortex expected for these species, and show that these match the sizes described in the literature. Our results suggest that the brains of great apes also scale linearly in their numbers of neurons like other primate brains, including humans. The conformity of great apes and humans to the linear cellular scaling rules that apply to other primates that diverged earlier in primate evolution indicates that prehistoric Homo species as well as other hominins must have had brains that conformed to the same scaling rules, irrespective of their body size. We then used those scaling rules and published estimated brain volumes for various hominin species to predict the numbers of neurons that composed their brains. We predict that Homo heidelbergensis and Homo neanderthalensis had brains with approximately 80 billion neurons, within the range of variation found in modern Homo sapiens. We propose that while the cellular scaling rules that apply to the primate brain have remained stable in hominin evolution (since they

  7. Positive correlation between ADAR expression and its targets suggests a complex regulation mediated by RNA editing in the human brain

    Science.gov (United States)

    Liscovitch, Noa; Bazak, Lily; Levanon, Erez Y; Chechik, Gal

    2014-01-01

    A-to-I RNA editing by adenosine deaminases acting on RNA is a post-transcriptional modification that is crucial for normal life and development in vertebrates. RNA editing has been shown to be very abundant in the human transcriptome, specifically at the primate-specific Alu elements. The functional role of this wide-spread effect is still not clear; it is believed that editing of transcripts is a mechanism for their down-regulation via processes such as nuclear retention or RNA degradation. Here we combine 2 neural gene expression datasets with genome-level editing information to examine the relation between the expression of ADAR genes with the expression of their target genes. Specifically, we computed the spatial correlation across structures of post-mortem human brains between ADAR and a large set of targets that were found to be edited in their Alu repeats. Surprisingly, we found that a large fraction of the edited genes are positively correlated with ADAR, opposing the assumption that editing would reduce expression. When considering the correlations between ADAR and its targets over development, 2 gene subsets emerge, positively correlated and negatively correlated with ADAR expression. Specifically, in embryonic time points, ADAR is positively correlated with many genes related to RNA processing and regulation of gene expression. These findings imply that the suggested mechanism of regulation of expression by editing is probably not a global one; ADAR expression does not have a genome wide effect reducing the expression of editing targets. It is possible, however, that RNA editing by ADAR in non-coding regions of the gene might be a part of a more complex expression regulation mechanism. PMID:25692240

  8. Morphometric variability of precuneus in relation to gender and the hemisphere of human brain

    OpenAIRE

    Spasojević Goran; Malobabić Slobodan; Šuščević Dušan; Miljković Željka

    2004-01-01

    Precuneus, a quadrangular gyrus of the medial surface of the human parietal lobe, is bound by three primary brain sulci and by superior hemispheric border. Precise encephalometric data about precuneus are important in the studies of brain lateralization, sex dimorphism, and brain functions in general. In this study, total and visible (exstrasulcal) surface area of the precuneus were measured on 50 brains of the adult persons (31 male, and 29 female), together with the investigation of its rel...

  9. The distribution of melanopsin (OPN4) protein in the human brain.

    Science.gov (United States)

    Nissilä, Juuso S; Mänttäri, Satu K; Särkioja, Terttu T; Tuominen, Hannu J; Takala, Timo E; Kiviniemi, Vesa J; Sormunen, Raija T; Saarela, Seppo Y O; Timonen, Markku J

    2017-01-01

    Until now, melanopsin (OPN4) - a specialized photopigment being responsive especially to blue light wavelengths - has not been found in the human brain at protein level outside the retina. More specifically, OPN4 has only been found in about 2% of retinal ganglion cells (i.e. in intrinsically photosensitive retinal ganglion cells), and in a subtype of retinal cone-cells. Given that Allen Institute for Brain Science has described a wide distribution of OPN4 mRNA in two human brains, we aimed to investigate whether OPN4 is present in the human brain also at protein level. Western blotting and immunohistochemistry, as well as immunoelectron microscopy, were used to analyse the existence and distribution of OPN4 protein in 18 investigated areas of the human brain in samples obtained in forensic autopsies from 10 male subjects (54 ± 3.5 years). OPN4 protein expression was found in all subjects, and, furthermore, in 5 out of 10 subjects in all investigated brain areas localized in membranous compartments and cytoplasmic vesicles of neurons. To our opinion, the wide distribution of OPN4 in central areas of the human brain evokes a question whether ambient light has important straight targets in the human brain outside the retinohypothalamic tract (RHT). Further studies are, however, needed to investigate the putative physiological phototransductive actions of inborn OPN4 protein outside the RHT in the human brain.

  10. 5-HT radioligands for human brain imaging with PET and SPECT

    DEFF Research Database (Denmark)

    Paterson, Louise M; Kornum, Birgitte R; Nutt, David J

    2013-01-01

    The serotonergic system plays a key modulatory role in the brain and is the target for many drug treatments for brain disorders either through reuptake blockade or via interactions at the 14 subtypes of 5-HT receptors. This review provides the history and current status of radioligands used...... for positron emission tomography (PET) and single photon emission computerized tomography (SPECT) imaging of human brain serotonin (5-HT) receptors, the 5-HT transporter (SERT), and 5-HT synthesis rate. Currently available radioligands for in vivo brain imaging of the 5-HT system in humans include antagonists...... to image serotonergic targets is of high interest, and successful evaluation in humans is leading to invaluable insight into normal and abnormal brain function, emphasizing the need for continued development of both SPECT and PET radioligands for human brain imaging....

  11. Comparative analysis of the macroscale structural connectivity in the macaque and human brain.

    Directory of Open Access Journals (Sweden)

    Alexandros Goulas

    2014-03-01

    Full Text Available The macaque brain serves as a model for the human brain, but its suitability is challenged by unique human features, including connectivity reconfigurations, which emerged during primate evolution. We perform a quantitative comparative analysis of the whole brain macroscale structural connectivity of the two species. Our findings suggest that the human and macaque brain as a whole are similarly wired. A region-wise analysis reveals many interspecies similarities of connectivity patterns, but also lack thereof, primarily involving cingulate regions. We unravel a common structural backbone in both species involving a highly overlapping set of regions. This structural backbone, important for mediating information across the brain, seems to constitute a feature of the primate brain persevering evolution. Our findings illustrate novel evolutionary aspects at the macroscale connectivity level and offer a quantitative translational bridge between macaque and human research.

  12. Human Emotion Detection via Brain Waves Study by Using Electroencephalogram (EEG)

    National Research Council Canada - National Science Library

    W.O. A.S. Wan Ismail; M. Hanif; S. B. Mohamed; Noraini Hamzah; Zairi Ismael Rizman

    2016-01-01

    .... This research was conducted to detect or identify human emotion via the study of brain waves. In addition, the research aims to develop computer software that can detect human emotions quickly and easily...

  13. Mapping a2 Adrenoceptors of the Human Brain with 11C-Yohimbine

    DEFF Research Database (Denmark)

    Nahimi, Adjmal; Jakobsen, Steen; Munk, Ole

    2015-01-01

    A previous study from this laboratory suggested that 11C-yohimbine, a selective α2-adrenoceptor antagonist, is an appropriate ligand for PET of α2 adrenoceptors that passes readily from blood to brain tissue in pigs but not in rodents. To test usefulness in humans, we determined blood–brain...... adrenoceptors in human brain had the highest values in cortical areas and hippocampus, with moderate values in subcortical structures, as found also in vitro. The results confirm the usefulness of the tracer 11C-yohimbine for mapping α2 adrenoceptors in human brain in vivo....

  14. Studying frequency processing of the brain to enhance long-term memory and develop a human brain protocol.

    Science.gov (United States)

    Friedrich, Wernher; Du, Shengzhi; Balt, Karlien

    2015-01-01

    The temporal lobe in conjunction with the hippocampus is responsible for memory processing. The gamma wave is involved with this process. To develop a human brain protocol, a better understanding of the relationship between gamma and long-term memory is vital. A more comprehensive understanding of the human brain and specific analogue waves it uses will support the development of a human brain protocol. Fifty-eight participants aged between 6 and 60 years participated in long-term memory experiments. It is envisaged that the brain could be stimulated through binaural beats (sound frequency) at 40 Hz (gamma) to enhance long-term memory capacity. EEG recordings have been transformed to sound and then to an information standard, namely ASCII. Statistical analysis showed a proportional relationship between long-term memory and gamma activity. Results from EEG recordings indicate a pattern. The pattern was obtained through the de-codification of an EEG recording to sound and then to ASCII. Stimulation of gamma should enhance long term memory capacity. More research is required to unlock the human brains' protocol key. This key will enable the processing of information directly to and from human memory via gamma, the hippocampus and the temporal lobe.

  15. Virtopsy: postmortem imaging of laryngeal foreign bodies.

    Science.gov (United States)

    Oesterhelweg, Lars; Bolliger, Stephan A; Thali, Michael J; Ross, Steffen

    2009-05-01

    Death from corpora aliena in the larynx is a well-known entity in forensic pathology. The correct diagnosis of this cause of death is difficult without an autopsy, and misdiagnoses by external examination alone are common. To determine the postmortem usefulness of modern imaging techniques in the diagnosis of foreign bodies in the larynx, multislice computed tomography, magnetic resonance imaging, and postmortem full-body computed tomography-angiography were performed. Three decedents with a suspected foreign body in the larynx underwent the 3 different imaging techniques before medicolegal autopsy. Multislice computed tomography has a high diagnostic value in the noninvasive localization of a foreign body and abnormalities in the larynx. The differentiation between neoplasm or soft foreign bodies (eg, food) is possible, but difficult, by unenhanced multislice computed tomography. By magnetic resonance imaging, the discrimination of the soft tissue structures and soft foreign bodies is much easier. In addition to the postmortem multislice computed tomography, the combination with postmortem angiography will increase the diagnostic value. Postmortem, cross-sectional imaging methods are highly valuable procedures for the noninvasive detection of corpora aliena in the larynx.

  16. Steady-state properties of sodium channels from healthy and tumorous human brain

    NARCIS (Netherlands)

    Frenkel, C.; Wartenberg, H. C.; Duch, D. S.; Urban, B. W.

    1998-01-01

    This extensive bilayer study of unpurified human brain channels from non-diseased and tumorous human brain involves more than 300 lipid bilayer experiments. Single channel conductances and subconductances, single channel fractional open times, the voltage-dependence of tetrodotoxin (TTX) block and

  17. Noninvasive quantification of human brain antioxidant concentrations after an intravenous bolus of vitamin C

    Science.gov (United States)

    Background: Until now, antioxidant based initiatives for preventing dementia have lacked a means to detect deficiency or measure pharmacologic effect in the human brain in situ. Objective: Our objective was to apply a novel method to measure key human brain antioxidant concentrations throughout the ...

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

    Science.gov (United States)

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

    2015-10-01

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

  19. The human sexual response cycle : Brain imaging evidence linking sex to other pleasures

    NARCIS (Netherlands)

    Georgiadis, J. R.; Kringelbach, M. L.

    Sexual behavior is critical to species survival, yet comparatively little is known about the neural mechanisms in the human brain. Here we systematically review the existing human brain imaging literature on sexual behavior and show that the functional neuroanatomy of sexual behavior is comparable

  20. Temperament, character and serotonin activity in the human brain

    DEFF Research Database (Denmark)

    Tuominen, L; Salo, J; Hirvonen, J

    2013-01-01

    The psychobiological model of personality by Cloninger and colleagues originally hypothesized that interindividual variability in the temperament dimension 'harm avoidance' (HA) is explained by differences in the activity of the brain serotonin system. We assessed brain serotonin transporter (5-HTT...

  1. Increasing honesty in humans with noninvasive brain stimulation.

    Science.gov (United States)

    Maréchal, Michel André; Cohn, Alain; Ugazio, Giuseppe; Ruff, Christian C

    2017-04-25

    Honesty plays a key role in social and economic interactions and is crucial for societal functioning. However, breaches of honesty are pervasive and cause significant societal and economic problems that can affect entire nations. Despite its importance, remarkably little is known about the neurobiological mechanisms supporting honest behavior. We demonstrate that honesty can be increased in humans with transcranial direct current stimulation (tDCS) over the right dorsolateral prefrontal cortex. Participants (n = 145) completed a die-rolling task where they could misreport their outcomes to increase their earnings, thereby pitting honest behavior against personal financial gain. Cheating was substantial in a control condition but decreased dramatically when neural excitability was enhanced with tDCS. This increase in honesty could not be explained by changes in material self-interest or moral beliefs and was dissociated from participants' impulsivity, willingness to take risks, and mood. A follow-up experiment (n = 156) showed that tDCS only reduced cheating when dishonest behavior benefited the participants themselves rather than another person, suggesting that the stimulated neural process specifically resolves conflicts between honesty and material self-interest. Our results demonstrate that honesty can be strengthened by noninvasive interventions and concur with theories proposing that the human brain has evolved mechanisms dedicated to control complex social behaviors.

  2. Absence of human cytomegalovirus infection in childhood brain tumors.

    Science.gov (United States)

    Sardi, Iacopo; Lucchesi, Maurizio; Becciani, Sabrina; Facchini, Ludovica; Guidi, Milena; Buccoliero, Anna Maria; Moriondo, Maria; Baroni, Gianna; Stival, Alessia; Farina, Silvia; Genitori, Lorenzo; de Martino, Maurizio

    2015-01-01

    Human cytomegalovirus (HCMV) is a common human pathogen which induces different clinical manifestations related to the age and the immune conditions of the host. HCMV infection seems to be involved in the pathogenesis of adult glioblastomas. The aim of our study was to detect the presence of HCMV in high grade gliomas and other pediatric brain tumors. This hypothesis might have important therapeutic implications, offering a new target for adjuvant therapies. Among 106 pediatric patients affected by CNS tumors we selected 27 patients with a positive HCMV serology. The serological analysis revealed 7 patients with positive HCMV IGG (≥14 U/mL), whom had also a high HCMV IgG avidity, suggesting a more than 6 months-dated infection. Furthermore, HCMV IGM were positive (≥22 U/mL) in 20 patients. Molecular and immunohistochemical analyses were performed in all the 27 samples. Despite a positive HCMV serology, confirmed by ELISA, no viral DNA was shown at the PCR analysis in the patients' neoplastic cells. At immunohistochemistry, no expression of HCMV antigens was observed in tumoral cells. Our results are in agreement with recent results in adults which did not evidence the presence of HCMV genome in glioblastoma lesions. We did not find any correlation between HCMV infection and pediatric CNS tumors.

  3. Evidence for Functional Networks within the Human Brain's White Matter.

    Science.gov (United States)

    Peer, Michael; Nitzan, Mor; Bick, Atira S; Levin, Netta; Arzy, Shahar

    2017-07-05

    brain. However, most fMRI studies ignored a major part of the brain, the white-matter, discarding signals from it as arising from noise. Here we use resting-state fMRI data from 176 subjects to show that signals from the human white-matter contain meaningful information. We identify 12 functional networks composed of interacting long-distance white-matter tracts. Moreover, we show that these networks are highly correlated to resting-state gray-matter networks, highlighting their functional role. Our findings enable reinterpretation of many existing fMRI datasets, and suggest a new way to explore the white-matter role in cognition and its disturbances in neuropsychiatric disorders. Copyright © 2017 the authors 0270-6474/17/376394-14$15.00/0.

  4. Exceptional evolutionary divergence of human muscle and brain metabolomes parallels human cognitive and physical uniqueness

    DEFF Research Database (Denmark)

    Bozek, Katarzyna; Wei, Yuning; Yan, Zheng

    2014-01-01

    Metabolite concentrations reflect the physiological states of tissues and cells. However, the role of metabolic changes in species evolution is currently unknown. Here, we present a study of metabolome evolution conducted in three brain regions and two non-neural tissues from humans, chimpanzees......, macaque monkeys, and mice based on over 10,000 hydrophilic compounds. While chimpanzee, macaque, and mouse metabolomes diverge following the genetic distances among species, we detect remarkable acceleration of metabolome evolution in human prefrontal cortex and skeletal muscle affecting neural and energy...... metabolism pathways. These metabolic changes could not be attributed to environmental conditions and were confirmed against the expression of their corresponding enzymes. We further conducted muscle strength tests in humans, chimpanzees, and macaques. The results suggest that, while humans are characterized...

  5. Exceptional evolutionary divergence of human muscle and brain metabolomes parallels human cognitive and physical uniqueness.

    Directory of Open Access Journals (Sweden)

    Katarzyna Bozek

    2014-05-01

    Full Text Available Metabolite concentrations reflect the physiological states of tissues and cells. However, the role of metabolic changes in species evolution is currently unknown. Here, we present a study of metabolome evolution conducted in three brain regions and two non-neural tissues from humans, chimpanzees, macaque monkeys, and mice based on over 10,000 hydrophilic compounds. While chimpanzee, macaque, and mouse metabolomes diverge following the genetic distances among species, we detect remarkable acceleration of metabolome evolution in human prefrontal cortex and skeletal muscle affecting neural and energy metabolism pathways. These metabolic changes could not be attributed to environmental conditions and were confirmed against the expression of their corresponding enzymes. We further conducted muscle strength tests in humans, chimpanzees, and macaques. The results suggest that, while humans are characterized by superior cognition, their muscular performance might be markedly inferior to that of chimpanzees and macaque monkeys.

  6. Exceptional Evolutionary Divergence of Human Muscle and Brain Metabolomes Parallels Human Cognitive and Physical Uniqueness

    Science.gov (United States)

    Bozek, Katarzyna; Wei, Yuning; Yan, Zheng; Liu, Xiling; Xiong, Jieyi; Sugimoto, Masahiro; Tomita, Masaru; Pääbo, Svante; Pieszek, Raik; Sherwood, Chet C.; Hof, Patrick R.; Ely, John J.; Steinhauser, Dirk; Willmitzer, Lothar; Bangsbo, Jens; Hansson, Ola; Call, Josep; Giavalisco, Patrick; Khaitovich, Philipp

    2014-01-01

    Metabolite concentrations reflect the physiological states of tissues and cells. However, the role of metabolic changes in species evolution is currently unknown. Here, we present a study of metabolome evolution conducted in three brain regions and two non-neural tissues from humans, chimpanzees, macaque monkeys, and mice based on over 10,000 hydrophilic compounds. While chimpanzee, macaque, and mouse metabolomes diverge following the genetic distances among species, we detect remarkable acceleration of metabolome evolution in human prefrontal cortex and skeletal muscle affecting neural and energy metabolism pathways. These metabolic changes could not be attributed to environmental conditions and were confirmed against the expression of their corresponding enzymes. We further conducted muscle strength tests in humans, chimpanzees, and macaques. The results suggest that, while humans are characterized by superior cognition, their muscular performance might be markedly inferior to that of chimpanzees and macaque monkeys. PMID:24866127

  7. Fractional Diffusion Based Modelling and Prediction of Human Brain Response to External Stimuli

    Directory of Open Access Journals (Sweden)

    Hamidreza Namazi

    2015-01-01

    Full Text Available Human brain response is the result of the overall ability of the brain in analyzing different internal and external stimuli and thus making the proper decisions. During the last decades scientists have discovered more about this phenomenon and proposed some models based on computational, biological, or neuropsychological methods. Despite some advances in studies related to this area of the brain research, there were fewer efforts which have been done on the mathematical modeling of the human brain response to external stimuli. This research is devoted to the modeling and prediction of the human EEG signal, as an alert state of overall human brain activity monitoring, upon receiving external stimuli, based on fractional diffusion equations. The results of this modeling show very good agreement with the real human EEG signal and thus this model can be used for many types of applications such as prediction of seizure onset in patient with epilepsy.

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

    OpenAIRE

    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 higher quality of life for the inhabitants of these regions combined with a healthy environment. To reach this goal, the project group will study the effects of brain drain/brain gain, co-ordinate appro...

  9. Endocannabinoids modulate human blood–brain barrier permeability in vitro

    Science.gov (United States)

    Hind, William H; Tufarelli, Cristina; Neophytou, Maria; Anderson, Susan I; England, Timothy J; O'Sullivan, Saoirse E

    2015-01-01

    Background and Purpose Endocannabinoids alter permeability at various epithelial barriers, and cannabinoid receptors and endocannabinoid levels are elevated by stroke, with potential neuroprotective effects. We therefore explored the role of endocannabinoids in modulating blood–brain barrier (BBB) permeability in normal conditions and in an ischaemia/reperfusion model. Experimental Approach Human brain microvascular endothelial cell and astrocyte co-cultures modelled the BBB. Ischaemia was modelled by oxygen-glucose deprivation (OGD) and permeability was measured by transepithelial electrical resistance. Endocannabinoids or endocannabinoid-like compounds were assessed for their ability to modulate baseline permeability or OGD-induced hyperpermeability. Target sites of action were investigated using receptor antagonists and subsequently identified with real-time PCR. Key Results Anandamide (10 μM) and oleoylethanolamide (OEA, 10 μM) decreased BBB permeability (i.e. increased resistance). This was mediated by cannabinoid CB2 receptors, transient receptor potential vanilloid 1 (TRPV1) channels, calcitonin gene-regulated peptide (CGRP) receptor (anandamide only) and PPARα (OEA only). Application of OEA, palmitoylethanolamide (both PPARα mediated) or virodhamine (all 10 μM) decreased the OGD-induced increase in permeability during reperfusion. 2-Arachidonoyl glycerol, noladin ether and oleamide did not affect BBB permeability in normal or OGD conditions. N-arachidonoyl-dopamine increased permeability through a cytotoxic mechanism. PPARα and γ, CB1 receptors, TRPV1 channels and CGRP receptors were expressed in both cell types, but mRNA for CB2 receptors was only present in astrocytes. Conclusion and Implication The endocannabinoids may play an important modulatory role in normal BBB physiology, and also afford protection to the BBB during ischaemic stroke, through a number of target sites. PMID:25651941

  10. Endocannabinoids modulate human blood-brain barrier permeability in vitro.

    Science.gov (United States)

    Hind, William H; Tufarelli, Cristina; Neophytou, Maria; Anderson, Susan I; England, Timothy J; O'Sullivan, Saoirse E

    2015-06-01

    Endocannabinoids alter permeability at various epithelial barriers, and cannabinoid receptors and endocannabinoid levels are elevated by stroke, with potential neuroprotective effects. We therefore explored the role of endocannabinoids in modulating blood-brain barrier (BBB) permeability in normal conditions and in an ischaemia/reperfusion model. Human brain microvascular endothelial cell and astrocyte co-cultures modelled the BBB. Ischaemia was modelled by oxygen-glucose deprivation (OGD) and permeability was measured by transepithelial electrical resistance. Endocannabinoids or endocannabinoid-like compounds were assessed for their ability to modulate baseline permeability or OGD-induced hyperpermeability. Target sites of action were investigated using receptor antagonists and subsequently identified with real-time PCR. Anandamide (10 μM) and oleoylethanolamide (OEA, 10 μM) decreased BBB permeability (i.e. increased resistance). This was mediated by cannabinoid CB2 receptors, transient receptor potential vanilloid 1 (TRPV1) channels, calcitonin gene-regulated peptide (CGRP) receptor (anandamide only) and PPARα (OEA only). Application of OEA, palmitoylethanolamide (both PPARα mediated) or virodhamine (all 10 μM) decreased the OGD-induced increase in permeability during reperfusion. 2-Arachidonoyl glycerol, noladin ether and oleamide did not affect BBB permeability in normal or OGD conditions. N-arachidonoyl-dopamine increased permeability through a cytotoxic mechanism. PPARα and γ, CB1 receptors, TRPV1 channels and CGRP receptors were expressed in both cell types, but mRNA for CB2 receptors was only present in astrocytes. The endocannabinoids may play an important modulatory role in normal BBB physiology, and also afford protection to the BBB during ischaemic stroke, through a number of target sites. © 2015 The Authors. British Journal of Pharmacology published by John Wiley & Sons Ltd on behalf of The British Pharmacological Society.

  11. Human-specific hypomethylation of CENPJ, a key brain size regulator.

    Science.gov (United States)

    Shi, Lei; Lin, Qiang; Su, Bing

    2014-03-01

    Both the enlarged brain and