Science.gov

Sample records for human brain morphology

  1. Increased morphological asymmetry, evolvability and plasticity in human brain evolution

    PubMed Central

    Gómez-Robles, Aida; Hopkins, William D.; Sherwood, Chet C.

    2013-01-01

    The study of hominin brain evolution relies mostly on evaluation of the endocranial morphology of fossil skulls. However, only some general features of external brain morphology are evident from endocasts, and many anatomical details can be difficult or impossible to examine. In this study, we use geometric morphometric techniques to evaluate inter- and intraspecific differences in cerebral morphology in a sample of in vivo magnetic resonance imaging scans of chimpanzees and humans, with special emphasis on the study of asymmetric variation. Our study reveals that chimpanzee–human differences in cerebral morphology are mainly symmetric; by contrast, there is continuity in asymmetric variation between species, with humans showing an increased range of variation. Moreover, asymmetric variation does not appear to be the result of allometric scaling at intraspecific levels, whereas symmetric changes exhibit very slight allometric effects within each species. Our results emphasize two key properties of brain evolution in the hominine clade: first, evolution of chimpanzee and human brains (and probably their last common ancestor and related species) is not strongly morphologically constrained, thus making their brains highly evolvable and responsive to selective pressures; second, chimpanzee and, especially, human brains show high levels of fluctuating asymmetry indicative of pronounced developmental plasticity. We infer that these two characteristics can have a role in human cognitive evolution. PMID:23615289

  2. Patterns of differences in brain morphology in humans as compared to extant apes

    PubMed Central

    Aldridge, Kristina

    2010-01-01

    Although human evolution is characterized by a vast increase in brain size, it is not clear whether or not certain regions of the brain are enlarged disproportionately in humans, or how this enlargement relates to differences in overall neural morphology. The aim of this study is to determine whether or not there are specific suites of features that distinguish the morphology of the human brain from that of apes. The study sample consists of whole brain, in vivo magnetic resonance images (MRIs) of anatomically modern humans (Homo sapiens sapiens) and five ape species (gibbons, orangutans, gorillas, chimpanzees, bonobos). Twenty-nine 3D landmarks, including surface and internal features of the brain were located on 3D MRI reconstructions of each individual using MEASURE software. Landmark coordinate data were scaled for differences in size and analyzed using Euclidean Distance Matrix Analysis (EDMA) to statistically compare the brains of each non-human ape species to the human sample. Results of analyses show both a pattern of brain morphology that is consistently different between all apes and humans, as well as patterns that differ among species. Further, both the consistent and species-specific patterns include cortical and subcortical features. The pattern that remains consistent across species indicates a morphological reorganization of 1) relationships between cortical and subcortical frontal structures, 2) expansion of the temporal lobe and location of the amygdala, and 3) expansion of the anterior parietal region. Additionally, results demonstrate that, although there is a pattern of morphology that uniquely defines the human brain, there are also patterns that uniquely differentiate human morphology from the morphology of each non-human ape species, indicating that reorganization of neural morphology occurred at the evolutionary divergence of each of these groups. PMID:21056456

  3. Early Parental Care Is Important for Hippocampal Maturation: Evidence from Brain Morphology in Humans

    PubMed Central

    Rao, Hengyi; Betancourt, Laura; Giannetta, Joan M.; Brodsky, Nancy L.; Korczykowski, Marc; Avants, Brian B.; Gee, James C.; Wang, Jiongjiong; Hurt, Hallam; Detre, John A.; Farah, Martha J.

    2009-01-01

    The effects of early life experience on later brain structure and function have been studied extensively in animals, yet the relationship between childhood experience and normal brain development in humans remains largely unknown. Using a unique longitudinal data set including ecologically valid in-home measures of early experience during childhood (at age 4 and 8 years) and high-resolution structural brain imaging during adolescence (mean age 14 years), we examined the effects on later brain morphology of two dimensions of early experience: parental nurturance and environmental stimulation. Parental nurturance at age 4 predicts the volume of the left hippocampus in adolescence, with better nurturance associated with smaller hippocampal volume. In contrast, environmental stimulation did not correlate with hippocampal volume. Moreover, the association between hippocampal volume and parental nurturance disappears at age 8, supporting the existence of a sensitive developmental period for brain maturation. These findings indicate that variation in normal childhood experience is associated with differences in brain morphology, and hippocampal volume is specifically associated with early parental nurturance. Our results provide neuroimaging evidence supporting the important role of warm parental care during early childhood for brain maturation. PMID:19595774

  4. A mechanical model predicts morphological abnormalities in the developing human brain

    NASA Astrophysics Data System (ADS)

    Budday, Silvia; Raybaud, Charles; Kuhl, Ellen

    2014-07-01

    The developing human brain remains one of the few unsolved mysteries of science. Advancements in developmental biology, neuroscience, and medical imaging have brought us closer than ever to understand brain development in health and disease. However, the precise role of mechanics throughout this process remains underestimated and poorly understood. Here we show that mechanical stretch plays a crucial role in brain development. Using the nonlinear field theories of mechanics supplemented by the theory of finite growth, we model the human brain as a living system with a morphogenetically growing outer surface and a stretch-driven growing inner core. This approach seamlessly integrates the two popular but competing hypotheses for cortical folding: axonal tension and differential growth. We calibrate our model using magnetic resonance images from very preterm neonates. Our model predicts that deviations in cortical growth and thickness induce morphological abnormalities. Using the gyrification index, the ratio between the total and exposed surface area, we demonstrate that these abnormalities agree with the classical pathologies of lissencephaly and polymicrogyria. Understanding the mechanisms of cortical folding in the developing human brain has direct implications in the diagnostics and treatment of neurological disorders, including epilepsy, schizophrenia, and autism.

  5. A mechanical model predicts morphological abnormalities in the developing human brain

    PubMed Central

    Budday, Silvia; Raybaud, Charles; Kuhl, Ellen

    2014-01-01

    The developing human brain remains one of the few unsolved mysteries of science. Advancements in developmental biology, neuroscience, and medical imaging have brought us closer than ever to understand brain development in health and disease. However, the precise role of mechanics throughout this process remains underestimated and poorly understood. Here we show that mechanical stretch plays a crucial role in brain development. Using the nonlinear field theories of mechanics supplemented by the theory of finite growth, we model the human brain as a living system with a morphogenetically growing outer surface and a stretch-driven growing inner core. This approach seamlessly integrates the two popular but competing hypotheses for cortical folding: axonal tension and differential growth. We calibrate our model using magnetic resonance images from very preterm neonates. Our model predicts that deviations in cortical growth and thickness induce morphological abnormalities. Using the gyrification index, the ratio between the total and exposed surface area, we demonstrate that these abnormalities agree with the classical pathologies of lissencephaly and polymicrogyria. Understanding the mechanisms of cortical folding in the developing human brain has direct implications in the diagnostics and treatment of neurological disorders, including epilepsy, schizophrenia, and autism. PMID:25008163

  6. Morphology and morphometry of the human embryonic brain: A three-dimensional analysis.

    PubMed

    Shiraishi, N; Katayama, A; Nakashima, T; Yamada, S; Uwabe, C; Kose, K; Takakuwa, T

    2015-07-15

    The three-dimensional dynamics and morphology of the human embryonic brain have not been previously analyzed using modern imaging techniques. The morphogenesis of the cerebral vesicles and ventricles was analyzed using images derived from human embryo specimens from the Kyoto Collection, which were acquired with a magnetic resonance microscope equipped with a 2.35-T superconducting magnet. A total of 101 embryos between Carnegie stages (CS) 13 and 23, without apparent morphological damage or torsion in the brain ventricles and axes, were studied. To estimate the uneven development of the cerebral vesicles, the volumes of the whole embryo and brain, prosencephalon, mesencephalon, and rhombencephalon with their respective ventricles were measured using image analyzing Amira™ software. The brain volume, excluding the ventricles (brain tissue), was 1.15 ± 0.43 mm(3) (mean ± SD) at CS13 and increased exponentially to 189.10 ± 36.91 mm(3) at CS23, a 164.4-fold increase, which is consistent with the observed morphological changes. The mean volume of the prosencephalon was 0.26 ± 0.15 mm(3) at CS13. The volume increased exponentially until CS23, when it reached 110.99 ± 27.58 mm(3). The mean volumes of the mesencephalon and rhombencephalon were 0.20 ± 0.07 mm(3) and 0.69 ± 0.23 mm(3) at CS13, respectively; the volumes reached 21.86 ± 3.30 mm(3) and 56.45 ± 7.64 mm(3) at CS23, respectively. The ratio of the cerebellum to the rhombencephalon was approximately 7.2% at CS20, and increased to 12.8% at CS23. The ratio of the volume of the cerebral vesicles to that of the whole embryo remained nearly constant between CS15 and CS23 (11.6-15.5%). The non-uniform thickness of the brain tissue during development, which may indicate the differentiation of the brain, was visualized with surface color mapping by thickness. At CS23, the basal regions of the prosencephalon and rhombencephalon were thicker than the corresponding dorsal regions. The brain was further studied by

  7. Morphological patterns of the intraparietal sulcus and the anterior intermediate parietal sulcus of Jensen in the human brain.

    PubMed

    Zlatkina, Veronika; Petrides, Michael

    2014-12-22

    Distinct parts of the intraparietal sulcal cortex contribute to sensorimotor integration and visual spatial attentional processing. A detailed examination of the morphological relations of the different segments of the complex intraparietal sulcal region in the human brain in standard stereotaxic space, which is a prerequisite for detailed structure-to-function studies, is not available. This study examined the intraparietal sulcus (IPS) and the related sulcus of Jensen in magnetic resonance imaging brain volumes registered in the Montreal Neurological Institute stereotaxic space. It was demonstrated that the IPS is divided into two branches: the anterior ramus and the posterior ramus of the IPS, often separated by a submerged gyral passage. The sulcus of Jensen emerges between the anterior and posterior rami of the IPS, and its ventral end is positioned between the first and second caudal branches of the superior temporal sulcus. In a small number of brains, the sulcus of Jensen may merge superficially with the first caudal branch of the superior temporal sulcus. The above morphological findings are discussed in relation to previously reported functional neuroimaging findings and provide the basis for future exploration of structure-to-function relations in the posterior parietal region of individual subjects. PMID:25377465

  8. Visualization of perivascular spaces in the human brain at 7T: sequence optimization and morphology characterization.

    PubMed

    Zong, Xiaopeng; Park, Sang Hyun; Shen, Dinggang; Lin, Weili

    2016-01-15

    Noninvasive imaging of perivascular spaces (PVSs) may provide useful insights into their role in normal brain physiology and diseases. Fast MRI sequences with sub-millimeter spatial resolutions and high contrast-to-noise ratio (CNR) are required for accurate delineation of PVS in human. To achieve the optimal condition for PVS imaging at 7T, we carried out detailed simulation and experimental studies to characterize the dependence of CNR on imaging sequences (T1 versus T2-weighted) and sequence parameters. In addition, PVSs were segmented semi-automatically, which revealed much larger numbers of PVSs in young healthy subjects (age 21-37years) than previously reported. To the best of our knowledge, our study provides, for the first time, detailed length, volume, and diameter distributions of PVS in the white matter and subcortical nuclei, which can serve as a reference for future studies of PVS abnormalities under diseased conditions. PMID:26520772

  9. Effects of omega-3 polyunsaturated fatty acids on human brain morphology and function: What is the evidence?

    PubMed

    Bos, Dienke J; van Montfort, Simone J T; Oranje, Bob; Durston, Sarah; Smeets, Paul A M

    2016-03-01

    Public opinion and media coverage suggest that there are benefits of long-chain ω-3 polyunsaturated fatty acid (LC-PUFA) intake on brain functioning. However, it is an open question whether this is indeed the case. Therefore, we reviewed the evidence for effects of ω-3 LC-PUFA on human brain morphology and function. We included studies on (1) naturalistic long-term ω-3 LC-PUFA intake during life (2) the effects of short-term ω-3 LC-PUFA supplementation in healthy subjects and (3) the effects of ω-3 LC-PUFA supplementation as alternative or add-on treatment for psychiatric or neurological disorders. To date, 24 studies have been published on the effect of ω-3 LC-PUFA on brain function and structure. Findings from naturalistic studies and clinical trials in healthy individuals indicate that ω-3 LC-PUFA intake may be associated with increased functional activation of the prefrontal cortex in children, and greater gray matter volume and white matter integrity during aging. However, most naturalistic studies were cross-sectional or did not find any effect on cognition. As such, it is hard to estimate the magnitude of any beneficial effects. Furthermore, there is only limited evidence to support that ω-3 LC-PUFA supplementation is beneficial in brain disorders, such as Alzheimer's Disease, Attention Deficit/Hyperactivity Disorder, Major Depressive Disorder and schizophrenia. Overall, the literature suggests that sensitivity to supplementation may vary over development, and as a consequence of brain disorders. The biological mechanisms underlying any (beneficial) effects ω-3 LC-PUFAs on the brain are currently unknown and need to be investigated. PMID:26742901

  10. Emerging brain morphologies from axonal elongation

    PubMed Central

    Holland, Maria A.; Miller, Kyle E.; Kuhl, Ellen

    2015-01-01

    Understanding the characteristic morphology of our brain remains a challenging, yet important task in human evolution, developmental biology, and neurosciences. Mathematical modeling shapes our understanding of cortical folding and provides functional relations between cortical wavelength, thickness, and stiffness. Yet, current mathematical models are phenomenologically isotropic and typically predict non-physiological, periodic folding patterns. Here we establish a mechanistic model for cortical folding, in which macroscopic changes in white matter volume are a natural consequence of microscopic axonal growth. To calibrate our model, we consult axon elongation experiments in chick sensory neurons. We demonstrate that a single parameter, the axonal growth rate, explains a wide variety of in vitro conditions including immediate axonal thinning and gradual thickness restoration. We embed our axonal growth model into a continuum model for brain development using axonal orientation distributions motivated by diffusion spectrum imaging. Our simulations suggest that white matter anisotropy - as an emergent property from directional axonal growth - intrinsically induces symmetry breaking, and predicts more physiological, less regular morphologies with regionally varying gyral wavelengths and sulcal depths. Mechanistic modeling of brain development could establish valuable relationships between brain connectivity, brain anatomy, and brain function. PMID:25824370

  11. BrainPrint: A Discriminative Characterization of Brain Morphology

    PubMed Central

    Wachinger, Christian; Golland, Polina; Kremen, William; Fischl, Bruce; Reuter, Martin

    2015-01-01

    We introduce BrainPrint, a compact and discriminative representation of brain morphology. BrainPrint captures shape information of an ensemble of cortical and subcortical structures by solving the eigenvalue problem of the 2D and 3D Laplace-Beltrami operator on triangular (boundary) and tetrahedral (volumetric) meshes. This discriminative characterization enables new ways to study the similarity between brains; the focus can either be on a specific brain structure of interest or on the overall brain similarity. We highlight four applications for BrainPrint in this article: (i) subject identification, (ii) age and sex prediction, (iii) brain asymmetry analysis, and (iv) potential genetic influences on brain morphology. The properties of BrainPrint require the derivation of new algorithms to account for the heterogeneous mix of brain structures with varying discriminative power. We conduct experiments on three datasets, including over 3000 MRI scans from the ADNI database, 436 MRI scans from the OASIS dataset, and 236 MRI scans from the VETSA twin study. All processing steps for obtaining the compact representation are fully automated, making this processing framework particularly attractive for handling large datasets. PMID:25613439

  12. Imaging brain morphology with ultrahigh-resolution optical coherence tomography

    NASA Astrophysics Data System (ADS)

    Bizheva, Kostadinka K.; Unterhuber, Angelika; Hermann, Boris; Povazay, Boris; Sattmann, Harald; Mei, Michael; Holzwarth, Ronald; Preusser, Matthias; Reitsamer, Herbert; Seefeldt, Michael; Menzel, Ralf; Budka, Herbert; Fercher, Adolf F.; Drexler, Wolfgang

    2003-10-01

    The morphology of healthy and pathological human brain tissue, as well as the brain structural organization of various animal models has been imaged in-vitro using ultrahigh resolution optical coherence tomography (UHR OCT). Micrometer-scale OCT resolution (< 2 μm axial resolution) was achieved at different central wavelengths by interfacing three state-of-the-art broad bandwidth light sources (Ti:Al2O3, λc = 790 nm, Δλ = 260 nm and Pout = 50 mW; PCF based laser, λc = 1150 nm, Δλ = 350 nm and Pout = 2 W; Fiber laser based light source, λc = 1350 nm, Δλ = 470 nm and Pout = 4 mW) to a modular free-space OCT system, utilizing a dynamic focusing and designed for optimal performance in the appropriate wavelength regions. Images acquired from a fixed honeybee brain demonstrated the ability of UHR OCT to image the globular structure of the brain, some fine morphological details such as the nerve fiber bundles connecting the medulla (visual center) to the honeybee eyes, and the interfaces between different tissue layers in the medulla. Tomograms of various human neuropathologies demonstrated the feasibility of UHR OCT to visualize morphological details such as small (~20 μm) calcifications typical for fibrous meningioma, and enlarged nuclei of cancer cells (~10-15 μm) characteristic for many other neuropathologies. In addition UHR OCT was used to image cellular morphology in living ganglion cells.

  13. Automatic Mapping Extraction from Multiecho T2-Star Weighted Magnetic Resonance Images for Improving Morphological Evaluations in Human Brain

    PubMed Central

    Yu, Shaode; Xie, Yaoqin

    2013-01-01

    Mapping extraction is useful in medical image analysis. Similarity coefficient mapping (SCM) replaced signal response to time course in tissue similarity mapping with signal response to TE changes in multiecho T2-star weighted magnetic resonance imaging without contrast agent. Since different tissues are with different sensitivities to reference signals, a new algorithm is proposed by adding a sensitivity index to SCM. It generates two mappings. One measures relative signal strength (SSM) and the other depicts fluctuation magnitude (FMM). Meanwhile, the new method is adaptive to generate a proper reference signal by maximizing the sum of contrast index (CI) from SSM and FMM without manual delineation. Based on four groups of images from multiecho T2-star weighted magnetic resonance imaging, the capacity of SSM and FMM in enhancing image contrast and morphological evaluation is validated. Average contrast improvement index (CII) of SSM is 1.57, 1.38, 1.34, and 1.41. Average CII of FMM is 2.42, 2.30, 2.24, and 2.35. Visual analysis of regions of interest demonstrates that SSM and FMM show better morphological structures than original images, T2-star mapping and SCM. These extracted mappings can be further applied in information fusion, signal investigation, and tissue segmentation. PMID:24379892

  14. Measuring Complexity of Mouse Brain Morphological Changes Using GeoEntropy

    NASA Astrophysics Data System (ADS)

    El-fiqi, Heba Z.; Pham, Tuan D.; Hattori, Haroldo T.; Crane, Denis I.

    2010-01-01

    Given the current emphasis on research into human neurodegenerative diseases, an effective computing approach for the analysis of complex brain morphological changes would represent a significant technological innovation. The availability of mouse models of such disorders provides an experimental system to test novel approaches to brain image analysis. Here we utilize a mouse model of a neurodegenerative disorder to model changes to cerebellar morphology during the postnatal period, and have applied the GeoEntropy algorithm to measure the complexity of morphological changes.

  15. Overlapping Trisomies for Human Chromosome 21 Orthologs Produce Similar Effects on Skull and Brain Morphology of Dp(16)1Yey and Ts65Dn Mice

    PubMed Central

    Ratliff, Tabetha S.; Reeves, Roger H.; Richtsmeier, Joan T.

    2014-01-01

    Trisomy 21 results in gene-dosage imbalance during embryogenesis and throughout life, ultimately causing multiple anomalies that contribute to the clinical manifestations of Down syndrome. Down syndrome is associated with manifestations of variable severity (e.g., heart anomalies, reduced growth, dental anomalies, shortened life-span). Craniofacial dysmorphology and cognitive dysfunction are consistently observed in all people with Down syndrome. Mouse models are useful for studying the effects of gene-dosage imbalance on development. We investigated quantitative changes in the skull and brain of the Dp(16) 1Yey Down syndrome mouse model and compared these mice to Ts65Dn and Ts1Cje mouse models. Three-dimensional microcomputed tomography images of Dp(16)1Yey and euploid mouse crania were morphometrically evaluated. Cerebellar cross-sectional area, Purkinje cell linear density, and granule cell density were evaluated relative to euploid littermates. Skulls of Dp(16)1Yey and Ts65Dn mice displayed similar changes in craniofacial morphology relative to their respective euploid littermates. Trisomy-based differences in brain morphology were also similar in Dp(16)1Yey and Ts65Dn mice. These results validate examination of the genetic basis for craniofacial and brain phenotypes in Dp(16)1Yey mice and suggest that they, like Ts65Dn mice, are valuable tools for modeling the effects of trisomy 21 on development. PMID:24788405

  16. Overlapping trisomies for human chromosome 21 orthologs produce similar effects on skull and brain morphology of Dp(16)1Yey and Ts65Dn mice.

    PubMed

    Starbuck, John M; Dutka, Tara; Ratliff, Tabetha S; Reeves, Roger H; Richtsmeier, Joan T

    2014-08-01

    Trisomy 21 results in gene-dosage imbalance during embryogenesis and throughout life, ultimately causing multiple anomalies that contribute to the clinical manifestations of Down syndrome. Down syndrome is associated with manifestations of variable severity (e.g., heart anomalies, reduced growth, dental anomalies, shortened life-span). Craniofacial dysmorphology and cognitive dysfunction are consistently observed in all people with Down syndrome. Mouse models are useful for studying the effects of gene-dosage imbalance on development. We investigated quantitative changes in the skull and brain of the Dp(16)1Yey Down syndrome mouse model and compared these mice to Ts65Dn and Ts1Cje mouse models. Three-dimensional micro-computed tomography images of Dp(16)1Yey and euploid mouse crania were morphometrically evaluated. Cerebellar cross-sectional area, Purkinje cell linear density, and granule cell density were evaluated relative to euploid littermates. Skulls of Dp(16)1Yey and Ts65Dn mice displayed similar changes in craniofacial morphology relative to their respective euploid littermates. Trisomy-based differences in brain morphology were also similar in Dp(16)1Yey and Ts65Dn mice. These results validate examination of the genetic basis for craniofacial and brain phenotypes in Dp(16)1Yey mice and suggest that they, like Ts65Dn mice, are valuable tools for modeling the effects of trisomy 21 on development. PMID:24788405

  17. Mapping Individual Brain Networks Using Statistical Similarity in Regional Morphology from MRI

    PubMed Central

    Kong, Xiang-zhen; Liu, Zhaoguo; Huang, Lijie; Wang, Xu; Yang, Zetian; Zhou, Guangfu; Zhen, Zonglei; Liu, Jia

    2015-01-01

    Representing brain morphology as a network has the advantage that the regional morphology of ‘isolated’ structures can be described statistically based on graph theory. However, very few studies have investigated brain morphology from the holistic perspective of complex networks, particularly in individual brains. We proposed a new network framework for individual brain morphology. Technically, in the new network, nodes are defined as regions based on a brain atlas, and edges are estimated using our newly-developed inter-regional relation measure based on regional morphological distributions. This implementation allows nodes in the brain network to be functionally/anatomically homogeneous but different with respect to shape and size. We first demonstrated the new network framework in a healthy sample. Thereafter, we studied the graph-theoretical properties of the networks obtained and compared the results with previous morphological, anatomical, and functional networks. The robustness of the method was assessed via measurement of the reliability of the network metrics using a test-retest dataset. Finally, to illustrate potential applications, the networks were used to measure age-related changes in commonly used network metrics. Results suggest that the proposed method could provide a concise description of brain organization at a network level and be used to investigate interindividual variability in brain morphology from the perspective of complex networks. Furthermore, the method could open a new window into modeling the complexly distributed brain and facilitate the emerging field of human connectomics. PMID:26536598

  18. Brain Morphological Defects in Prolidase Deficient Mice: First Report

    PubMed Central

    Insolia, V.

    2014-01-01

    Prolidase gene (PEPD) encodes prolidase enzyme, which is responsible for hydrolysis of dipeptides containing proline or hydroxypro-line at their C-terminal end. Mutations in PEPD gene cause, in human, prolidase deficiency (PD), a rare autosomal recessive disorder. PD patients show reduced or absent prolidase activity and a broad spectrum of phenotypic traits including various degrees of mental retardation. This is the first report correlating PD and brain damages using as a model system prolidase deficient mice, the so called dark-like (dal) mutant mice. We focused our attention on dal postnatal brain development, revealing a panel of different morphological defects in the cerebral and cerebellar cortices, such as undulations of the cerebral cortex, cell rarefaction, defects in cerebellar cortex lobulation, and blood vessels overgrowth. These anomalies might be ascribed to altered angiogenic process and loss of pial basement membrane integrity. Further studies will be directed to find a correlation between neuroarchitecture alterations and functional consequences. PMID:25308848

  19. Educating the Human Brain. Human Brain Development Series

    ERIC Educational Resources Information Center

    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…

  20. Modeling the brain morphology distribution in the general aging population

    NASA Astrophysics Data System (ADS)

    Huizinga, W.; Poot, D. H. J.; Roshchupkin, G.; Bron, E. E.; Ikram, M. A.; Vernooij, M. W.; Rueckert, D.; Niessen, W. J.; Klein, S.

    2016-03-01

    Both normal aging and neurodegenerative diseases such as Alzheimer's disease cause morphological changes of the brain. To better distinguish between normal and abnormal cases, it is necessary to model changes in brain morphology owing to normal aging. To this end, we developed a method for analyzing and visualizing these changes for the entire brain morphology distribution in the general aging population. The method is applied to 1000 subjects from a large population imaging study in the elderly, from which 900 were used to train the model and 100 were used for testing. The results of the 100 test subjects show that the model generalizes to subjects outside the model population. Smooth percentile curves showing the brain morphology changes as a function of age and spatiotemporal atlases derived from the model population are publicly available via an interactive web application at agingbrain.bigr.nl.

  1. Developmental Dyslexia, Neurolinguistic Theory and Deviations in Brain Morphology.

    ERIC Educational Resources Information Center

    Hynd, George W.; And Others

    1991-01-01

    Reviews computer tomography and magnetic resonance imaging studies examining deviations in brain morphology. Discusses methodological and technical issues. Concludes that dyslexics show variations in specific brain regions. Suggests that neuroimaging procedures appear to provide direct evidence supporting the importance of deviations in normal…

  2. Segmentation of human brain using structural MRI.

    PubMed

    Helms, Gunther

    2016-04-01

    Segmentation of human brain using structural MRI is a key step of processing in imaging neuroscience. The methods have undergone a rapid development in the past two decades and are now widely available. This non-technical review aims at providing an overview and basic understanding of the most common software. Starting with the basis of structural MRI contrast in brain and imaging protocols, the concepts of voxel-based and surface-based segmentation are discussed. Special emphasis is given to the typical contrast features and morphological constraints of cortical and sub-cortical grey matter. In addition to the use for voxel-based morphometry, basic applications in quantitative MRI, cortical thickness estimations, and atrophy measurements as well as assignment of cortical regions and deep brain nuclei are briefly discussed. Finally, some fields for clinical applications are given. PMID:26739264

  3. Morphology and histology of chimpanzee primary visual striate cortex indicate that brain reorganization predated brain expansion in early hominid evolution.

    PubMed

    Holloway, Ralph L; Broadfield, Douglas C; Yuan, Michael S

    2003-07-01

    Human brain evolution is characterized by an overall increase in brain size, cerebral reorganization, and cerebral lateralization. It is generally understood when brain enlargement occurred during human evolution. However, issues concerning cerebral reorganization and hemispheric lateralization are more difficult to determine from brain endocasts, and they are topics of considerable debate. One region of the cerebral cortex that may represent the earliest evidence for brain reorganization is the primary visual cortex (PVC), or area 17 of Brodmann. In nonhuman primates, this region is larger in volume (demarcated anteriorly by the lunate sulcus), and extends further rostrally than it does in modern humans. In early hominid fossil (Australopithecus) endocasts, this region appears to occupy a smaller area compared to that in nonhuman primates. Some have argued that the brain first underwent size expansion prior to reorganization, while others maintain that reorganization predated brain expansion. To help resolve this question, we provide a description of two male, common chimpanzee (Pan troglodytes) brains, YN77-111 and YN92-115, which clearly display a more posterior lunate sulcal morphology than seen in other chimpanzees. These data show that neurogenetic variability exists in chimpanzees, and that significant differences in organization (e.g., a reduced PVC) can predate brain enlargement. While the human brain has experienced numerous expansion and reorganization events throughout evolution, the data from these two chimpanzees offer significant support for the hypothesis that the neurogenetic basis for brain reorganization was present in our early fossil ancestors (i.e., the australopithecines) prior to brain enlargement. PMID:12808644

  4. A Morphological Theory of Human Hearing

    NASA Astrophysics Data System (ADS)

    Pamieri, Paolo

    2011-11-01

    The interdisciplinary project motivating the work discussed in this paper aims at developing an integrated framework of ideas for human hearing research. The novelty of the project consists in combining the history and philosophy of sound perception in humans with psychoacoustics and mechanics of hearing. In this paper, I present a morphological theory of human hearing, which replaces the concept of tonopic representation in the cochlea which the concept of morphological representation.

  5. Magnetite biomineralization in the human brain.

    PubMed Central

    Kirschvink, J L; Kobayashi-Kirschvink, A; Woodford, B J

    1992-01-01

    Although the mineral magnetite (Fe3O4) is precipitated biochemically by bacteria, protists, and a variety of animals, it has not been documented previously in human tissue. Using an ultrasensitive superconducting magnetometer in a clean-lab environment, we have detected the presence of ferromagnetic material in a variety of tissues from the human brain. Magnetic particle extracts from solubilized brain tissues examined with high-resolution transmission electron microscopy, electron diffraction, and elemental analyses identify minerals in the magnetite-maghemite family, with many of the crystal morphologies and structures resembling strongly those precipitated by magnetotactic bacteria and fish. These magnetic and high-resolution transmission electron microscopy measurements imply the presence of a minimum of 5 million single-domain crystals per gram for most tissues in the brain and greater than 100 million crystals per gram for pia and dura. Magnetic property data indicate the crystals are in clumps of between 50 and 100 particles. Biogenic magnetite in the human brain may account for high-field saturation effects observed in the T1 and T2 values of magnetic resonance imaging and, perhaps, for a variety of biological effects of low-frequency magnetic fields. Images PMID:1502184

  6. Systematic implications of brain morphology in potamotrygonidae (Chondrichthyes: Myliobatiformes).

    PubMed

    Fontenelle, João Pedro; de Carvalho, Marcelo R

    2016-02-01

    The gross brain morphology, brain proportions, and position of cranial nerves in all four genera (Potamotrygon, Plesiotrygon, Paratrygon, and Heliotrygon) and 11 of the species of the Neotropical stingray family Potamotrygonidae were studied to provide new characters that may have a bearing on internal potamotrygonid systematics. The brain was also studied in four other stingray (Myliobatiformes) genera (Hexatrygon, Taeniura, Dasyatis, and Gymnura) to provide a more inclusive phylogenetic context for the interpretation of features of the brain in potamotrygonids. Our results indicate, based on neuroanatomical characters, that the genera Paratrygon and Heliotrygon are sister groups, as are the genera Potamotrygon and Plesiotrygon, agreeing with previous morphological and molecular phylogenetic studies. Both groups of genera share distinct conditions of the olfactory tracts, telencephalon and its central nuclei, hypophysis and infundibulum, morphology and orientation of the metencephalic corpus cerebelli, orientation of the glossopharyngeal nerve, and overall encephalic proportions. The corpus cerebelli of Paratrygon and Heliotrygon is interpreted as being more similar to the general batoid condition and, given their phylogenetic position highly nested within stingrays, is considered secondarily derived, not plesiomorphically retained. Our observations of the corpus cerebelli of stingrays, including Hexatrygon, corroborate that the general stingray pattern previously advanced by Northcutt is derived among batoids. The morphology of the brain is shown to be a useful source of phylogenetically informative characters at lower hierarchical levels, such as between genera and species, and thus, has significant potential in phylogenetic studies of elasmobranchs. PMID:26592726

  7. Social cognition and brain morphology: implications for developmental brain dysfunction.

    PubMed

    Evans, David W; Lazar, Steven M; Boomer, K B; Mitchel, Aaron D; Michael, Andrew M; Moore, Gregory J

    2015-06-01

    The social-cognitive deficits associated with several neurodevelopmental and neuropsychiatric disorders have been linked to structural and functional brain anomalies. Given the recent appreciation for quantitative approaches to behavior, in this study we examined the brain-behavior links in social cognition in healthy young adults from a quantitative approach. Twenty-two participants were administered quantitative measures of social cognition, including the social responsiveness scale (SRS), the empathizing questionnaire (EQ) and the systemizing questionnaire (SQ). Participants underwent a structural, 3-T magnetic resonance imaging (MRI) procedure that yielded both volumetric (voxel count) and asymmetry indices. Model fitting with backward elimination revealed that a combination of cortical, limbic and striatal regions accounted for significant variance in social behavior and cognitive styles that are typically associated with neurodevelopmental and neuropsychiatric disorders. Specifically, as caudate and amygdala volumes deviate from the typical R > L asymmetry, and cortical gray matter becomes more R > L asymmetrical, overall SRS and Emotion Recognition scores increase. Social Avoidance was explained by a combination of cortical gray matter, pallidum (rightward asymmetry) and caudate (deviation from rightward asymmetry). Rightward asymmetry of the pallidum was the sole predictor of Interpersonal Relationships and Repetitive Mannerisms. Increased D-scores on the EQ-SQ, an indication of greater systemizing relative to empathizing, was also explained by deviation from the typical R > L asymmetry of the caudate.These findings extend the brain-behavior links observed in neurodevelopmental disorders to the normal distribution of traits in a healthy sample. PMID:24788335

  8. Food Web Structure Shapes the Morphology of Teleost Fish Brains.

    PubMed

    Edmunds, Nicholas B; McCann, Kevin S; Laberge, Frédéric

    2016-01-01

    Previous work showed that teleost fish brain size correlates with the flexible exploitation of habitats and predation abilities in an aquatic food web. Since it is unclear how regional brain changes contribute to these relationships, we quantitatively examined the effects of common food web attributes on the size of five brain regions in teleost fish at both within-species (plasticity or natural variation) and between-species (evolution) scales. Our results indicate that brain morphology is influenced by habitat use and trophic position, but not by the degree of littoral-pelagic habitat coupling, despite the fact that the total brain size was previously shown to increase with habitat coupling in Lake Huron. Intriguingly, the results revealed two potential evolutionary trade-offs: (i) relative olfactory bulb size increased, while relative optic tectum size decreased, across a trophic position gradient, and (ii) the telencephalon was relatively larger in fish using more littoral-based carbon, while the cerebellum was relatively larger in fish using more pelagic-based carbon. Additionally, evidence for a within-species effect on the telencephalon was found, where it increased in size with trophic position. Collectively, these results suggest that food web structure has fundamentally contributed to the shaping of teleost brain morphology. PMID:27216606

  9. Epigenetics in the Human Brain

    PubMed Central

    Houston, Isaac; Peter, Cyril J; Mitchell, Amanda; Straubhaar, Juerg; Rogaev, Evgeny; Akbarian, Schahram

    2013-01-01

    Many cellular constituents in the human brain permanently exit from the cell cycle during pre- or early postnatal development, but little is known about epigenetic regulation of neuronal and glial epigenomes during maturation and aging, including changes in mood and psychosis spectrum disorders and other cognitive or emotional disease. Here, we summarize the current knowledge base as it pertains to genome organization in the human brain, including the regulation of DNA cytosine methylation and hydroxymethylation, and a subset of (altogether >100) residue-specific histone modifications associated with gene expression, and silencing and various other functional chromatin states. We propose that high-resolution mapping of epigenetic markings in postmortem brain tissue or neural cultures derived from induced pluripotent cells (iPS), in conjunction with transcriptome profiling and whole-genome sequencing, will increasingly be used to define the molecular pathology of specific cases diagnosed with depression, schizophrenia, autism, or other major psychiatric disease. We predict that these highly integrative explorations of genome organization and function will provide an important alternative to conventional approaches in human brain studies, which mainly are aimed at uncovering group effects by diagnosis but generally face limitations because of cohort size. PMID:22643929

  10. Normalization of brain morphology after surgery in sagittal craniosynostosis.

    PubMed

    Brooks, Eric D; Yang, Jenny; Beckett, Joel S; Lacadie, Cheryl; Scheinost, Dustin; Persing, Sarah; Zellner, Elizabeth G; Oosting, Devon; Keifer, Cara; Friedman, Hannah E; Wyk, Brent Vander; Jou, Roger J; Sun, Haosi; Gary, Cyril; Duncan, Charles C; Constable, R Todd; Pelphrey, Kevin A; Persing, John A

    2016-04-01

    OBJECT Nonsyndromic craniosynostosis (NSC) is associated with significant learning disability later in life. Surgical reconstruction is typically performed before 1 year of age to correct the cranial vault morphology and to allow for normalized brain growth with the goal of improving cognitive function. Yet, no studies have assessed to what extent normalized brain growth is actually achieved. Recent advances in MRI have allowed for automated methods of objectively assessing subtle and pronounced brain morphological differences. The authors used one such technique, deformation-based morphometry (DBM) Jacobian mapping, to determine how previously treated adolescents with sagittal NSC (sNSC) significantly differ in brain anatomy compared with healthy matched controls up to 11.5 years after surgery. METHODS Eight adolescent patients with sNSC, previously treated via whole-vault cranioplasty at a mean age of 7 months, and 8 age- and IQ-matched control subjects without craniosynostosis (mean age for both groups = 12.3 years), underwent functional 3-T MRI. Statistically significant group tissue-volume differences were assessed using DBM, a whole-brain technique that estimates morphological differences between 2 groups at each voxel (p < 0.01). Group-wise Jacobian volume maps were generated using a spacing of 1.5 mm and a resolution of 1.05 × 1.05 × 1.05 mm(3). RESULTS There were no significant areas of volume reduction or expansion in any brain areas in adolescents with sNSC compared with controls at a significance level of p < 0.01. At the more liberal threshold of p < 0.05, two areas of brain expansion extending anteroposteriorly in the right temporooccipital and left frontoparietal regions appeared in patients with sNSC compared with controls. CONCLUSIONS Compared with previous reports on untreated infants with sNSC, adolescents with sNSC in this cohort had few areas of brain dysmorphology many years after surgery. This result suggests that comprehensive cranioplasty

  11. Brain bases of morphological processing in young children.

    PubMed

    Arredondo, Maria M; Ip, Ka I; Shih Ju Hsu, Lucy; Tardif, Twila; Kovelman, Ioulia

    2015-08-01

    How does the developing brain support the transition from spoken language to print? Two spoken language abilities form the initial base of child literacy across languages: knowledge of language sounds (phonology) and knowledge of the smallest units that carry meaning (morphology). While phonology has received much attention from the field, the brain mechanisms that support morphological competence for learning to read remain largely unknown. In the present study, young English-speaking children completed an auditory morphological awareness task behaviorally (n = 69, ages 6-12) and in fMRI (n = 16). The data revealed two findings: First, children with better morphological abilities showed greater activation in left temporoparietal regions previously thought to be important for supporting phonological reading skills, suggesting that this region supports multiple language abilities for successful reading acquisition. Second, children showed activation in left frontal regions previously found active in young Chinese readers, suggesting morphological processes for reading acquisition might be similar across languages. These findings offer new insights for developing a comprehensive model of how spoken language abilities support children's reading acquisition across languages. PMID:25930011

  12. Neurobiological origin of spurious brain morphological changes: A quantitative MRI study

    PubMed Central

    Lorio, Sara; Kherif, Ferath; Ruef, Anne; Melie‐Garcia, Lester; Frackowiak, Richard; Ashburner, John; Helms, Gunther

    2016-01-01

    Abstract The high gray‐white matter contrast and spatial resolution provided by T1‐weighted magnetic resonance imaging (MRI) has made it a widely used imaging protocol for computational anatomy studies of the brain. While the image intensity in T1‐weighted images is predominantly driven by T1, other MRI parameters affect the image contrast, and hence brain morphological measures derived from the data. Because MRI parameters are correlates of different histological properties of brain tissue, this mixed contribution hampers the neurobiological interpretation of morphometry findings, an issue which remains largely ignored in the community. We acquired quantitative maps of the MRI parameters that determine signal intensities in T1‐weighted images (R 1 (=1/T1), R 2*, and PD) in a large cohort of healthy subjects (n = 120, aged 18–87 years). Synthetic T1‐weighted images were calculated from these quantitative maps and used to extract morphometry features—gray matter volume and cortical thickness. We observed significant variations in morphometry measures obtained from synthetic images derived from different subsets of MRI parameters. We also detected a modulation of these variations by age. Our findings highlight the impact of microstructural properties of brain tissue—myelination, iron, and water content—on automated measures of brain morphology and show that microstructural tissue changes might lead to the detection of spurious morphological changes in computational anatomy studies. They motivate a review of previous morphological results obtained from standard anatomical MRI images and highlight the value of quantitative MRI data for the inference of microscopic tissue changes in the healthy and diseased brain. Hum Brain Mapp 37:1801–1815, 2016. © 2016 The Authors. Human Brain Mapping Published by Wiley Periodicals, Inc. PMID:26876452

  13. Neurobiological origin of spurious brain morphological changes: A quantitative MRI study.

    PubMed

    Lorio, Sara; Kherif, Ferath; Ruef, Anne; Melie-Garcia, Lester; Frackowiak, Richard; Ashburner, John; Helms, Gunther; Lutti, Antoine; Draganski, Bodgan

    2016-05-01

    The high gray-white matter contrast and spatial resolution provided by T1-weighted magnetic resonance imaging (MRI) has made it a widely used imaging protocol for computational anatomy studies of the brain. While the image intensity in T1-weighted images is predominantly driven by T1, other MRI parameters affect the image contrast, and hence brain morphological measures derived from the data. Because MRI parameters are correlates of different histological properties of brain tissue, this mixed contribution hampers the neurobiological interpretation of morphometry findings, an issue which remains largely ignored in the community. We acquired quantitative maps of the MRI parameters that determine signal intensities in T1-weighted images (R1 (=1/T1), R2 *, and PD) in a large cohort of healthy subjects (n = 120, aged 18-87 years). Synthetic T1-weighted images were calculated from these quantitative maps and used to extract morphometry features-gray matter volume and cortical thickness. We observed significant variations in morphometry measures obtained from synthetic images derived from different subsets of MRI parameters. We also detected a modulation of these variations by age. Our findings highlight the impact of microstructural properties of brain tissue-myelination, iron, and water content-on automated measures of brain morphology and show that microstructural tissue changes might lead to the detection of spurious morphological changes in computational anatomy studies. They motivate a review of previous morphological results obtained from standard anatomical MRI images and highlight the value of quantitative MRI data for the inference of microscopic tissue changes in the healthy and diseased brain. Hum Brain Mapp 37:1801-1815, 2016. © 2016 The Authors. Human Brain Mapping Published by Wiley Periodicals, Inc. PMID:26876452

  14. Structural Brain Correlates of Human Sleep Oscillations

    PubMed Central

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

    2014-01-01

    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. Grey 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, grey matter volume in bilateral hippocampus was associated with faster NREM sleep spindle frequencies. In contrast to spindles, grey 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. PMID:23770411

  15. Structural brain correlates of human sleep oscillations.

    PubMed

    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. PMID:23770411

  16. Physical biology of human brain development

    PubMed Central

    Budday, Silvia; Steinmann, Paul; Kuhl, Ellen

    2015-01-01

    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 toward 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 toward 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. PMID:26217183

  17. Physical biology of human brain development.

    PubMed

    Budday, Silvia; Steinmann, Paul; Kuhl, Ellen

    2015-01-01

    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 toward 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 toward 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. PMID:26217183

  18. A Direct Brain-to-Brain Interface in Humans

    PubMed Central

    Rao, Rajesh P. N.; Stocco, Andrea; Bryan, Matthew; Sarma, Devapratim; Youngquist, Tiffany M.; Wu, Joseph; Prat, Chantel S.

    2014-01-01

    We describe the first direct brain-to-brain interface in humans and present results from experiments involving six different subjects. Our non-invasive interface, demonstrated originally in August 2013, combines electroencephalography (EEG) for recording brain signals with transcranial magnetic stimulation (TMS) for delivering information to the brain. We illustrate our method using a visuomotor task in which two humans must cooperate through direct brain-to-brain communication to achieve a desired goal in a computer game. The brain-to-brain interface detects motor imagery in EEG signals recorded from one subject (the “sender”) and transmits this information over the internet to the motor cortex region of a second subject (the “receiver”). This allows the sender to cause a desired motor response in the receiver (a press on a touchpad) via TMS. We quantify the performance of the brain-to-brain interface in terms of the amount of information transmitted as well as the accuracies attained in (1) decoding the sender’s signals, (2) generating a motor response from the receiver upon stimulation, and (3) achieving the overall goal in the cooperative visuomotor task. Our results provide evidence for a rudimentary form of direct information transmission from one human brain to another using non-invasive means. PMID:25372285

  19. Morphology and digitally aided morphometry of the human paracentral lobule.

    PubMed

    Spasojević, Goran; Malobabic, Slobodan; Pilipović-Spasojević, Olivera; Djukić-Macut, Nataša; Maliković, Aleksandar

    2013-02-01

    The human paracentral lobule, the junction of the precentral and postcentral gyri at the medial hemispheric surface, contains several important functional regions, and its variable morphology requires exact morphological and quantitativedata. In order to obtain precise data we investigated the morphology of the paracentral lobule and quantified its visible (extrasulcal) surface. This surface corresponds to commonly used magnetic resonance imaging scout images. We studied 84 hemispheres of adult persons (42 brains; 26 males and 16 females; 20-65 years) fixed in neutral formalin for at least 4 weeks. The medial hemispheric surface was photographed at standard distance and each digital photo was calibrated. Using the intercommissural line system (commissura anterior-commissura posterior or CA-CP line), we performed standardised measurements of the paracentral lobule. Exact determination of its boundaries and morphological types was followed by digital morphometry of its extrasulcal surface using AutoCAD software. We found two distinct morphological types of the human paracentral lobule: continuous type, which was predominant (95.2%), and rare segmented type (4.8%). In hemispheres with segmented cingulate sulcus we also found the short transitional lobulo-limbic gyrus (13.1%). The mean extrasulcal surface of the left paracentral lobule was significantly larger, both in males (left 6.79 cm2 vs. right 5.76 cm2) and in females (left 6.05 cm2 vs. right 5.16 cm2). However, even larger average surfaces in males were not significantly different than the same in females. Reported morphological and quantitative data will be useful during diagnostics and treatment of pathologies affecting the human paracentral lobule, and in further studies of its cytoarchitectonic and functional parcellations. PMID:23749705

  20. Two phylogenetic specializations in the human brain.

    PubMed

    Allman, John; Hakeem, Atiya; Watson, Karli

    2002-08-01

    In this study, two anatomical specializations of the brain in apes and humans are considered. One of these is a whole cortical area located in the frontal polar cortex (Brodmann's area 10), and the other is a morphologically distinctive cell type, the spindle neuron of the anterior cingulate cortex. The authors suggest that the spindle cells may relay to other parts of the brain--especially to area 10, the outcome of processing within the anterior cingulate cortex. This relay conveys the motivation to act. It particularly concerns the recognition of having committed an error that leads to the initiation of adaptive responses to these adverse events so as to reduce error commission. This capacity is related to the development of self-control as an individual matures and gains social insight. Although the anterior cingulate deals with the individual's immediate response to changing conditions, area 10 is involved in the retrieval of memories from the individual's past experience and the capacity to plan adaptive responses. The authors suggest that these neurobehavioral specializations are crucial aspects of intelligence as defined as the capacity to make adaptive responses to changing conditions. The authors further hypothesize that these specializations facilitated the evolution of the unique capacity for the intergenerational transfer of the food and information characteristic of human extended families. PMID:12194502

  1. Neonatal Brain Tissue Classification with Morphological Adaptation and Unified Segmentation

    PubMed Central

    Beare, Richard J.; Chen, Jian; Kelly, Claire E.; Alexopoulos, Dimitrios; Smyser, Christopher D.; Rogers, Cynthia E.; Loh, Wai Y.; Matthews, Lillian G.; Cheong, Jeanie L. Y.; Spittle, Alicia J.; Anderson, Peter J.; Doyle, Lex W.; Inder, Terrie E.; Seal, Marc L.; Thompson, Deanne K.

    2016-01-01

    Measuring the distribution of brain tissue types (tissue classification) in neonates is necessary for studying typical and atypical brain development, such as that associated with preterm birth, and may provide biomarkers for neurodevelopmental outcomes. Compared with magnetic resonance images of adults, neonatal images present specific challenges that require the development of specialized, population-specific methods. This paper introduces MANTiS (Morphologically Adaptive Neonatal Tissue Segmentation), which extends the unified segmentation approach to tissue classification implemented in Statistical Parametric Mapping (SPM) software to neonates. MANTiS utilizes a combination of unified segmentation, template adaptation via morphological segmentation tools and topological filtering, to segment the neonatal brain into eight tissue classes: cortical gray matter, white matter, deep nuclear gray matter, cerebellum, brainstem, cerebrospinal fluid (CSF), hippocampus and amygdala. We evaluated the performance of MANTiS using two independent datasets. The first dataset, provided by the NeoBrainS12 challenge, consisted of coronal T2-weighted images of preterm infants (born ≤30 weeks' gestation) acquired at 30 weeks' corrected gestational age (n = 5), coronal T2-weighted images of preterm infants acquired at 40 weeks' corrected gestational age (n = 5) and axial T2-weighted images of preterm infants acquired at 40 weeks' corrected gestational age (n = 5). The second dataset, provided by the Washington University NeuroDevelopmental Research (WUNDeR) group, consisted of T2-weighted images of preterm infants (born <30 weeks' gestation) acquired shortly after birth (n = 12), preterm infants acquired at term-equivalent age (n = 12), and healthy term-born infants (born ≥38 weeks' gestation) acquired within the first 9 days of life (n = 12). For the NeoBrainS12 dataset, mean Dice scores comparing MANTiS with manual segmentations were all above 0.7, except for the cortical gray

  2. Human Brain Reacts to Transcranial Extraocular Light

    PubMed Central

    Sun, Lihua; Peräkylä, Jari; Kovalainen, Anselmi; Ogawa, Keith H.; Karhunen, Pekka J.; Hartikainen, Kaisa M.

    2016-01-01

    Transcranial extraocular light affects the brains of birds and modulates their seasonal changes in physiology and behavior. However, whether the human brain is sensitive to extraocular light is unknown. To test whether extraocular light has any effect on human brain functioning, we measured brain electrophysiology of 18 young healthy subjects using event-related potentials while they performed a visual attention task embedded with emotional distractors. Extraocular light delivered via ear canals abolished normal emotional modulation of attention related brain responses. With no extraocular light delivered, emotional distractors reduced centro-parietal P300 amplitude compared to neutral distractors. This phenomenon disappeared with extraocular light delivery. Extraocular light delivered through the ear canals was shown to penetrate at the base of the scull of a cadaver. Thus, we have shown that extraocular light impacts human brain functioning calling for further research on the mechanisms of action of light on the human brain. PMID:26910350

  3. Human Brain Reacts to Transcranial Extraocular Light.

    PubMed

    Sun, Lihua; Peräkylä, Jari; Kovalainen, Anselmi; Ogawa, Keith H; Karhunen, Pekka J; Hartikainen, Kaisa M

    2016-01-01

    Transcranial extraocular light affects the brains of birds and modulates their seasonal changes in physiology and behavior. However, whether the human brain is sensitive to extraocular light is unknown. To test whether extraocular light has any effect on human brain functioning, we measured brain electrophysiology of 18 young healthy subjects using event-related potentials while they performed a visual attention task embedded with emotional distractors. Extraocular light delivered via ear canals abolished normal emotional modulation of attention related brain responses. With no extraocular light delivered, emotional distractors reduced centro-parietal P300 amplitude compared to neutral distractors. This phenomenon disappeared with extraocular light delivery. Extraocular light delivered through the ear canals was shown to penetrate at the base of the scull of a cadaver. Thus, we have shown that extraocular light impacts human brain functioning calling for further research on the mechanisms of action of light on the human brain. PMID:26910350

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

    PubMed Central

    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

  5. Histology and Morphology of the Brain Subarachnoid Trabeculae

    PubMed Central

    Saboori, Parisa; Sadegh, Ali

    2015-01-01

    The interface between the brain and the skull consists of three fibrous tissue layers, dura mater, arachnoid, and pia mater, known as the meninges, and strands of collagen tissues connecting the arachnoid to the pia mater, known as trabeculae. The space between the arachnoid and the pia mater is filled with cerebrospinal fluid which stabilizes the shape and position of the brain during head movements or impacts. The histology and architecture of the subarachnoid space trabeculae in the brain are not well established in the literature. The only recognized fact about the trabeculae is that they are made of collagen fibers surrounded by fibroblast cells and they have pillar- and veil-like structures. In this work the histology and the architecture of the brain trabeculae were studied, via a series of in vivo and in vitro experiments using cadaveric and animal tissue. In the cadaveric study fluorescence and bright field microscopy were employed while scanning and transmission electron microscopy were used for the animal studies. The results of this study reveal that the trabeculae are collagen based type I, and their architecture is in the form of tree-shaped rods, pillars, and plates and, in some regions, they have a complex network morphology. PMID:26090230

  6. Brain development is similar in Neanderthals and modern humans.

    PubMed

    Ponce de León, Marcia S; Bienvenu, Thibaut; Akazawa, Takeru; Zollikofer, Christoph P E

    2016-07-25

    While the braincase of adult Neanderthals had a similar volume to that of modern humans from the same period, differences in endocranial shape suggest that brain morphology differed between modern humans and Neanderthals. When and how these differences arose during evolution and development is a topic of ongoing research, with potential implications for species-specific differences in brain and cognitive development, and in life history [1,2]. Earlier research suggested that Neanderthals followed an ancestral mode of brain development, similar to that of our closest living relatives, the chimpanzees [2-4]. Modern humans, by contrast, were suggested to follow a uniquely derived mode of brain development just after birth, giving rise to the characteristically globular shape of the adult human brain case [2,4,5]. Here, we re-examine this hypothesis using an extended sample of Neanderthal infants. We document endocranial development during the decisive first two years of postnatal life. The new data indicate that Neanderthals followed largely similar modes of endocranial development to modern humans. These findings challenge the notion that human brain and cognitive development after birth is uniquely derived [2,4]. PMID:27458909

  7. Atypical Cristae Morphology of Human Syncytiotrophoblast Mitochondria

    PubMed Central

    De Los Rios Castillo, Daniela; Zarco-Zavala, Mariel; Olvera-Sanchez, Sofia; Pardo, Juan Pablo; Juarez, Oscar; Martinez, Federico; Mendoza-Hernandez, Guillermo; García-Trejo, José J.; Flores-Herrera, Oscar

    2011-01-01

    Mitochondrial complexes I, III2, and IV from human cytotrophoblast and syncytiotrophoblast associate to form supercomplexes or respirasomes, with the following stoichiometries: I1:(III2)1 and I1:(III2)1–2:IV1–4. The content of respirasomes was similar in both cell types after isolating mitochondria. However, syncytiotrophoblast mitochondria possess low levels of dimeric complex V and do not have orthodox cristae morphology. In contrast, cytotrophoblast mitochondria show normal cristae morphology and a higher content of ATP synthase dimer. Consistent with the dimerizing role of the ATPase inhibitory protein (IF1) (García, J. J., Morales-Ríos, E., Cortés-Hernandez, P., and Rodríguez-Zavala, J. S. (2006) Biochemistry 45, 12695–12703), higher relative amounts of IF1 were observed in cytotrophoblast when compared with syncytiotrophoblast mitochondria. Therefore, there is a correlation between dimerization of complex V, IF1 expression, and the morphology of mitochondrial cristae in human placental mitochondria. The possible relationship between cristae architecture and the physiological function of the syncytiotrophoblast mitochondria is discussed. PMID:21572045

  8. Bazooka mediates secondary axon morphology in Drosophila brain lineages

    PubMed Central

    2011-01-01

    In the Drosophila brain, neural lineages project bundled axon tracts into a central neuropile. Each lineage exhibits a stereotypical branching pattern and trajectory, which distinguish it from other lineages. In this study, we used a multilineage approach to explore the neural function of the Par-complex member Par3/Bazooka in vivo. Drosophila bazooka is expressed in post-mitotic neurons of the larval brain and localizes within neurons in a lineage-dependent manner. The fact that multiple GAL4 drivers have been mapped to several lineages of the Drosophila brain enables investigation of the role of Bazooka from larval to adult stages Bazooka loss-of-function (LOF) clones had abnormal morphologies, including aberrant pathway choice of ventral projection neurons in the BAla1 lineage, ectopic branching in the DALv2 and BAmv1 lineages, and excess BLD5 lineage axon projections in the optic medulla. Exogenous expression of Bazooka protein in BAla1 neurons rescued defective guidance, supporting an intrinsic requirement for Bazooka in the post-mitotic neuron. Elimination of the Par-complex member Par6 recapitulated Bazooka phenotypes in some but not all lineages, suggesting that the Par complex functions in a lineage-dependent manner, and that Bazooka may act independently in some lineages. Importantly, this study highlights the potential of using a multilineage approach when studying gene function during neural development in Drosophila. PMID:21524279

  9. Bazooka mediates secondary axon morphology in Drosophila brain lineages.

    PubMed

    Spindler, Shana R; Hartenstein, Volker

    2011-01-01

    In the Drosophila brain, neural lineages project bundled axon tracts into a central neuropile. Each lineage exhibits a stereotypical branching pattern and trajectory, which distinguish it from other lineages. In this study, we used a multilineage approach to explore the neural function of the Par-complex member Par3/Bazooka in vivo. Drosophila bazooka is expressed in post-mitotic neurons of the larval brain and localizes within neurons in a lineage-dependent manner. The fact that multiple GAL4 drivers have been mapped to several lineages of the Drosophila brain enables investigation of the role of Bazooka from larval to adult stages Bazooka loss-of-function (LOF) clones had abnormal morphologies, including aberrant pathway choice of ventral projection neurons in the BAla1 lineage, ectopic branching in the DALv2 and BAmv1 lineages, and excess BLD5 lineage axon projections in the optic medulla. Exogenous expression of Bazooka protein in BAla1 neurons rescued defective guidance, supporting an intrinsic requirement for Bazooka in the post-mitotic neuron. Elimination of the Par-complex member Par6 recapitulated Bazooka phenotypes in some but not all lineages, suggesting that the Par complex functions in a lineage-dependent manner, and that Bazooka may act independently in some lineages. Importantly, this study highlights the potential of using a multilineage approach when studying gene function during neural development in Drosophila. PMID:21524279

  10. Brain morphological alternation in chronic pain patients with neuropathic characteristics

    PubMed Central

    Sugimine, Satomi; Kawamichi, Hiroaki; Obata, Hideaki; Saito, Shigeru

    2016-01-01

    Background Neuropathic characteristics are highly involved in the development of chronic pain both physically and psychologically. However, little is known about the relationship between neuropathic characteristics and brain morphological alteration. Objectives The aim of this study is to investigate the mechanisms of chronic pain development by examining the above-mentioned relationships by voxel-based morphometry in patients with chronic pain. Methods First, we assessed neuropathic characteristics using the painDETECT Questionnaire in 12 chronic pain patients. Second, to assess the gray matter volume changes by voxel-based morphometry, we conducted magnetic resonance imaging of the brain. We applied multiregression analysis of these two assessment methods. Results There were significant positive correlations between painDETECT Questionnaire scores and the gray matter volume in the bilateral anterior cingulate cortex and right posterior cingulate cortex. Conclusions Our findings suggest that neuropathic characteristics strongly affect the brain regions related to modulation of pain in patients with chronic pain and, therefore, contribute to the severity of chronic pain. PMID:27284013

  11. [Planimetric volumetry of human brains].

    PubMed

    Orthner, H; Seler, W

    1975-04-01

    1) Coronal sections measuring exactly 4 mm in thickness of 106 human brains (212 cerebral hemispheres) were cut with the Göttinger Hirnmakrotom. Planimetric volumetry of various macroscopically delineated structures was performed on photographs of the sections. 2) The volumes ovtained from 58 "normal cases" were used for determining preliminary standards as well as mean values and standard deviations for age and sex. The female-male ratio of the structures measured varies between 86 and 92%. Comparing right and left a predominance of the left pallidum for both sexes is apparent showing an error probability of less than 5%. In "normal" men a significant predominance of the rightsided frontal structures, located anterior to the anterior commissure, have been found (error probability of less than 1%). 3) Regarding the 48 "abnormal cases", striatum and pallidum show a uniform picture in Huntington's disease, namely an extreme shrinkage. The pallidum shrinks to a similar extent as the striatum, although its neurones are not substantially affected by this system atrophy. Other structures do not display similarly uniform changes in this disease. 4) In Parkinson's syndrome a tendency of the pallidum to enlarge -- though statistically not significant -- is seen. This raises the question whether a constitutional hyperplasia of this structure is sometimes involved in the pathogenesis. 5) In Pick's disease, it is not only the histologically impressive centers of shrinkage of the cerebral cortex that are atrophic, but, to a somewhat lesser degree, also the whole telencephalon. 6) In an 18-year-old girl with malignant obsessional neurosis (schizophrenia?) the volume of the striatum was highly above average values enlarged. 7) Bibliographical data of macroscopic-quantitative brain research reveal many problems which can be solved today due to improved methods. PMID:125721

  12. Morphological Features of the Neonatal Brain Following Exposure to Regional Anesthesia During Labor and Delivery

    PubMed Central

    Spann, Marisa N.; Serino, Dana; Bansal, Ravi; Hao, Xuejun; Nati, Giancarlo; Toth, Zachary; Walsh, Kirwan; Chiang, I-Chin; Sanchez-Peña, Juan; Liu, Jun; Kangarlu, Alayar; Liu, Feng; Duan, Yunsuo; Shova, Satie; Fried, Jane; Tau, Gregory Z.; Rosen, Tove S.; Peterson, Bradley S.

    2014-01-01

    Introduction Recent animal and human epidemiological studies suggest that early childhood exposure to anesthesia may have adverse effects on brain development. As more than 50% of pregnant women in the United States and one-third in the United Kingdom receive regional anesthesia during labor and delivery, understanding the effects of perinatal anesthesia on postnatal brain development has important public health relevance. Methods We used high-resolution Magnetic Resonance Imaging (MRI) to assess the effects of regional anesthesia during labor and delivery as part of a larger study of perinatal exposures on the morphological features of the neonatal brain. We mapped morphological features of the cortical surface in 37 healthy infants, 24 exposed and 13 unexposed to regional anesthesia at delivery, who were scanned within the first 6 weeks of life. Results Infants exposed to maternal anesthesia compared with unexposed infants had greater local volumes in portions of the frontal and occipital lobes bilaterally and right posterior portion of the cingulate gyrus. Longer durations of exposure to anesthesia correlated positively with local volumes in the occipital lobe. Conclusions Anesthesia exposure during labor and delivery was associated with larger volumes in portions of the frontal and occipital lobes and cingulate gyrus in neonates. Longitudinal MRI studies are needed to determine whether these morphological effects of anesthesia persist and what their consequences on cognition and behavior may be. PMID:25179140

  13. Three-dimensional assessment of brain tissue morphology

    NASA Astrophysics Data System (ADS)

    Müller, Bert; Germann, Marco; Jeanmonod, Daniel; Morel, Anne

    2006-08-01

    The microstructure of brain tissues becomes visible using different types of optical microscopy after the tissue sectioning. This preparation procedure introduces stress and strain in the anisotropic and inhomogeneous soft tissue slices, which are several 10 μm thick. Consequently, the three-dimensional dataset, generated out of the two-dimensional images with lateral submicrometer resolution, needs algorithms to correct the deformations, which can be significant for mellow tissue such as brain segments. The spatial resolution perpendicular to the slices is much worse with respect to the lateral sub-micrometer resolution. Therefore, we propose as complementary method the synchrotron-radiation-based micro computed tomography (SRμCT), which avoids any kind of preparation artifacts due to sectioning and histological processing and yields true micrometer resolution in the three orthogonal directions. The visualization of soft matter by the use of SRμCT, however, is often based on elaborate staining protocols, since the tissue exhibits (almost) the same x-ray absorption as the surrounding medium. Therefore, it is unexpected that human tissue from the pons and the medulla oblongata in phosphate buffer show several features such as the blood vessels and the inferior olivary nucleus without staining. The value of these tomograms lies especially in the precise non-rigid registration of the different sets of histological slices. Applications of this method to larger pieces of brain tissue, such as the human thalamus are planned in the context of stereotactic functional neurosurgery.

  14. Fast and intuitive segmentation of gyri of the human brain

    NASA Astrophysics Data System (ADS)

    Weiler, Florian; Hahn, Horst K.

    2015-03-01

    The cortical surface of the human brain consists of a large number of folds forming valleys and ridges, the gyri and sulci. Often, it is desirable to perform a segmentation of a brain image into these underlying structures in order to assess parameters relative to these functional components. Typical examples for this include measurements of cortical thickness for individual functional areas, or the correlation of functional areas derived from fMRI data to corresponding anatomical areas seen in structural imaging. In this paper, we present a novel interactive technique, that allows for fast and intuitive segmentation of these functional areas from T1-weighted MR images of the brain. Our segmentation approach is based exclusively on morphological image processing operations, eliminating the requirement for explicit reconstruction of the brains surface.

  15. Protein phosphorylation systems in postmortem human brain

    SciTech Connect

    Walaas, S.I.; Perdahl-Wallace, E.; Winblad, B.; Greengard, P. )

    1989-01-01

    Protein phosphorylation systems regulated by cyclic adenosine 3',5'-monophosphate (cyclic AMP), or calcium in conjunction with calmodulin or phospholipid/diacylglycerol, have been studied by phosphorylation in vitro of particulate and soluble fractions from human postmortem brain samples. One-dimensional or two-dimensional gel electrophoretic protein separations were used for analysis. Protein phosphorylation catalyzed by cyclic AMP-dependent protein kinase was found to be highly active in both particulate and soluble preparations throughout the human CNS, with groups of both widely distributed and region-specific substrates being observed in different brain nuclei. Dopamine-innervated parts of the basal ganglia and cerebral cortex contained the phosphoproteins previously observed in rodent basal ganglia. In contrast, calcium/phospholipid-dependent and calcium/calmodulin-dependent protein phosphorylation systems were less prominent in human postmortem brain than in rodent brain, and only a few widely distributed substrates for these protein kinases were found. Protein staining indicated that postmortem proteolysis, particularly of high-molecular-mass proteins, was prominent in deeply located, subcortical regions in the human brain. Our results indicate that it is feasible to use human postmortem brain samples, when obtained under carefully controlled conditions, for qualitative studies on brain protein phosphorylation. Such studies should be of value in studies on human neurological and/or psychiatric disorders.

  16. Transcriptional neoteny in the human brain

    PubMed Central

    Somel, Mehmet; Franz, Henriette; Yan, Zheng; Lorenc, Anna; Guo, Song; Giger, Thomas; Kelso, Janet; Nickel, Birgit; Dannemann, Michael; Bahn, Sabine; Webster, Maree J.; Weickert, Cynthia S.; Lachmann, Michael; Pääbo, Svante; Khaitovich, Philipp

    2009-01-01

    In development, timing is of the utmost importance, and the timing of developmental processes often changes as organisms evolve. In human evolution, developmental retardation, or neoteny, has been proposed as a possible mechanism that contributed to the rise of many human-specific features, including an increase in brain size and the emergence of human-specific cognitive traits. We analyzed mRNA expression in the prefrontal cortex of humans, chimpanzees, and rhesus macaques to determine whether human-specific neotenic changes are present at the gene expression level. We show that the brain transcriptome is dramatically remodeled during postnatal development and that developmental changes in the human brain are indeed delayed relative to other primates. This delay is not uniform across the human transcriptome but affects a specific subset of genes that play a potential role in neural development. PMID:19307592

  17. Mapping genetic influences on human brain structure.

    PubMed

    Thompson, Paul; Cannon, Tyrone D; Toga, Arthur W

    2002-01-01

    Recent advances in brain imaging and genetics have empowered the mapping of genetic and environmental influences on the human brain. These techniques shed light on the 'nature/nurture' debate, revealing how genes determine individual differences in intelligence quotient (IQ) or risk for disease. They visualize which aspects of brain structure and function are heritable, and to what degree, linking these features with behavioral or cognitive traits or disease phenotypes. In genetically transmitted disorders such as schizophrenia, patterns of brain structure can be associated with increased disease liability, and sites can be mapped where non-genetic triggers may initiate disease. We recently developed a large-scale computational brain atlas, including data components from the Finnish Twin registry, to store information on individual variations in brain structure and their heritability. Algorithms from random field theory, anatomical modeling, and population genetics were combined to detect a genetic continuum in which brain structure is heavily genetically determined in some areas but not others. These algorithmic advances motivate studies of disease in which the normative atlas acts as a quantitative reference for the heritability of structural differences and deficits in patient populations. The resulting genetic brain maps isolate biological markers for inherited traits and disease susceptibility, which may serve as targets for genetic linkage and association studies. Computational methods from brain imaging and genetics can be fruitfully merged, to shed light on the inheritance of personality differences and behavioral traits, and the genetic transmission of diseases that affect the human brain. PMID:12553492

  18. Human Misato regulates mitochondrial distribution and morphology

    SciTech Connect

    Kimura, Masashi . E-mail: yo@gifu-u.ac.jp; Okano, Yukio

    2007-04-15

    Misato of Drosophila melanogaster and Saccharomyces cerevisiae DML1 are conserved proteins having a homologous region with a part of the GTPase family that includes eukaryotic tubulin and prokaryotic FtsZ. We characterized human Misato sharing homology with Misato of D. melanogaster and S. cerevisiae DML1. Tissue distribution of Misato exhibited ubiquitous distribution. Subcellular localization of the protein studied using anti-Misato antibody suggested that it is localized to the mitochondria. Further experiments of fractionating mitochondria revealed that Misato was localized to the outer membrane. The transfection of Misato siRNA led to growth deficiencies compared with control siRNA transfected HeLa cells, and the Misato-depleted HeLa cells showed apoptotic nuclear fragmentation resulting in cell death. After silencing of Misato, the filamentous mitochondrial network disappeared and fragmented mitochondria were observed, indicating human Misato has a role in mitochondrial fusion. To examine the effects of overexpression, COS-7 cells were transfected with cDNA encoding EGFP-Misato. Its overexpression resulted in the formation of perinuclear aggregations of mitochondria in these cells. The Misato-overexpressing cells showed low viability and had no nuclei or a small and structurally unusual ones. These results indicated that human Misato has a role(s) in mitochondrial distribution and morphology and that its unregulated expression leads to cell death.

  19. Determining correspondence in 3-D MR brain images using attribute vectors as morphological signatures of voxels.

    PubMed

    Xue, Zhong; Shen, Dinggang; Davatzikos, Christos

    2004-10-01

    Finding point correspondence in anatomical images is a key step in shape analysis and deformable registration. This paper proposes an automatic correspondence detection algorithm for intramodality MR brain images of different subjects using wavelet-based attribute vectors (WAVs) defined on every image voxel. The attribute vector (AV) is extracted from the wavelet subimages and reflects the image structure in a large neighborhood around the respective voxel in a multiscale fashion. It plays the role of a morphological signature for each voxel, and our goal is, therefore, to make it distinctive of the respective voxel. Correspondence is then determined from similarities of AVs. By incorporating the prior knowledge of the spatial relationship among voxels, the ability of the proposed algorithm to find anatomical correspondence is further improved. Experiments with MR images of human brains show that the algorithm performs similarly to experts, even for complex cortical structures. PMID:15493695

  20. Genomic imprinting effects of the X-chromosome on brain morphology

    PubMed Central

    Lepage, Jean-Francois; Hong, David S.; Mazaika, Paul K.; Raman, Mira; Sheau, Kristen; Marzelli, Matthew J.; Hallmayer, Joachim; Reiss, Allan L.

    2013-01-01

    There is increasing evidence that genomic imprinting, a process by which certain genes are expressed in a parent-of-origin specific manner, can influence neurogenetic and psychiatric manifestations. While some data suggest possible imprinting effects of the X-chromosome on physical and cognitive characteristics in human, there is no compelling evidence that X-linked imprinting affects brain morphology. To address this issue, we investigated regional cortical volume, thickness and surface area in 27 healthy controls and 40 prepubescent girls with Turner syndrome (TS), a condition caused by the absence of one X-chromosome. Of the young girls with TS, 23 inherited their X-chromosome from their mother (Xm) and 17 from their father (Xp). Our results confirm the existence of significant differences in brain morphology between girls with TS and controls, and reveal the presence of a putative imprinting effect among the TS groups: girls with Xp demonstrated thicker cortex than those with Xm in the temporal regions bilaterally, while Xm individuals showed bilateral enlargement of gray matter volume in the superior frontal regions in comparison to Xp. These data suggest the existence of imprinting effects of the X-chromosome that influence both cortical thickness and volume during early brain development, and help to explain variability in cognitive and behavioral manifestations of TS with regard to the parental origin of the X-chromosome. PMID:23658194

  1. Morphology and biomechanics of human heart

    NASA Astrophysics Data System (ADS)

    Chelnokova, Natalia O.; Golyadkina, Anastasiya A.; Kirillova, Irina V.; Polienko, Asel V.; Ivanov, Dmitry V.

    2016-03-01

    Object of study: A study of the biomechanical characteristics of the human heart ventricles was performed. 80 hearts were extracted during autopsy of 80 corpses of adults (40 women and 40 men) aged 31-70 years. The samples were investigated in compliance with the recommendations of the ethics committee. Methods: Tension and compression tests were performed with help of the uniaxial testing machine Instron 5944. Cardiometry was also performed. Results: In this work, techniques for human heart ventricle wall biomechanical properties estimation were developed. Regularities of age and gender variability in deformative and strength properties of the right and left ventricle walls were found. These properties were characterized by a smooth growth of myocardial tissue stiffness and resistivity at a relatively low strain against reduction in their strength and elasticity from 31-40 to 61-70 years. It was found that tissue of the left ventricle at 61-70 years had a lower stretchability and strength compared with tissues of the right ventricle and septum. These data expands understanding of the morphological organization of the heart ventricles, which is very important for the development of personalized medicine. Taking into account individual, age and gender differences of the heart ventricle tissue biomechanical characteristics allows to rationally choosing the type of patching materials during reconstructive operations on heart.

  2. The human parental brain: In vivo neuroimaging

    PubMed Central

    Swain, James E.

    2015-01-01

    Interacting parenting thoughts and behaviors, supported by key brain circuits, critically shape human infants’ current and future behavior. Indeed, the parent–infant relationship provides infants with their first social environment, forming templates for what they can expect from others, how to interact with them and ultimately how they go on to themselves to be parents. This review concentrates on magnetic resonance imaging experiments of the human parent brain, which link brain physiology with parental thoughts and behaviors. After reviewing brain imaging techniques, certain social cognitive and affective concepts are reviewed, including empathy and trust—likely critical to parenting. Following that is a thorough study-by-study review of the state-of-the-art with respect to human neuroimaging studies of the parental brain—from parent brain responses to salient infant stimuli, including emotionally charged baby cries and brief visual stimuli to the latest structural brain studies. Taken together, this research suggests that networks of highly conserved hypothalamic–midbrain–limbic–paralimbic–cortical circuits act in concert to support parental brain responses to infants, including circuits for limbic emotion response and regulation. Thus, a model is presented in which infant stimuli activate sensory analysis brain regions, affect corticolimbic limbic circuits that regulate emotional response, motivation and reward related to their infant, ultimately organizing parenting impulses, thoughts and emotions into coordinated behaviors as a map for future studies. Finally, future directions towards integrated understanding of the brain basis of human parenting are outlined with profound implications for understanding and contributing to long term parent and infant mental health. PMID:21036196

  3. Morphological and behavioral markers of environmentally induced retardation of brain development: an animal model.

    PubMed Central

    Altman, J

    1987-01-01

    In most neurotoxicological studies morphological assessment focuses on pathological effects, like degenerative changes in neuronal perikarya, axonopathy, demyelination, and glial and endothelial cell reactions. Similarly, the assessment of physiological and behavioral effects center on evident neurological symptoms, like EEG and EMG abnormalities, resting and intention tremor, abnormal gait, and abnormal reflexes. This paper reviews briefly another central nervous system target of harmful environmental agents, which results in behavioral abnormalities without any qualitatively evident neuropathology. This is called microneuronal hypoplasia, a retardation of brain development characterized by a quantitative reduction in the normal population of late-generated, short-axoned neurons in specific brain regions. Correlated descriptive and experimental neurogenetic studies in the rat have established that all the cerebellar granule cells and a very high proportion of hippocampal granule cells are produced postnatally, and that focal, low-dose X-irradiation either of the cerebellum or of the hippocampus after birth selectively interferes with the acquisition of the full complement of granule cells (microneuronal hypoplasia). Subsequent behavioral investigations showed that cerebellar microneuronal hypoplasia results in profound hyperactivity without motor abnormalities, while hippocampal microneuronal hypoplasia results in hyperactivity, as well as attentional and learning deficits. There is much indirect clinical evidence that various harmful environmental agents affecting the pregnant mother and/or the infant lead to such childhood disorders as hyperactivity and attentional and learning disorders. As the developing human brain is more mature at birth than the rat brain, the risk for microneuronal hypoplasia and consequent behavioral disorders may be highest at late stages of fetal development, in prematurely born and small-for-weight infants, and during the early stages

  4. Human brain mapping: Experimental and computational approaches

    SciTech Connect

    Wood, C.C.; George, J.S.; Schmidt, D.M.; Aine, C.J.; Sanders, J.; Belliveau, J.

    1998-11-01

    This is the final report of a three-year, Laboratory-Directed Research and Development (LDRD) project at the Los Alamos National Laboratory (LANL). This program developed project combined Los Alamos' and collaborators' strengths in noninvasive brain imaging and high performance computing to develop potential contributions to the multi-agency Human Brain Project led by the National Institute of Mental Health. The experimental component of the project emphasized the optimization of spatial and temporal resolution of functional brain imaging by combining: (a) structural MRI measurements of brain anatomy; (b) functional MRI measurements of blood flow and oxygenation; and (c) MEG measurements of time-resolved neuronal population currents. The computational component of the project emphasized development of a high-resolution 3-D volumetric model of the brain based on anatomical MRI, in which structural and functional information from multiple imaging modalities can be integrated into a single computational framework for modeling, visualization, and database representation.

  5. Symmetry and asymmetry in the human brain

    NASA Astrophysics Data System (ADS)

    Hugdahl, Kenneth

    2005-10-01

    Structural and functional asymmetry in the human brain and nervous system is reviewed in a historical perspective, focusing on the pioneering work of Broca, Wernicke, Sperry, and Geschwind. Structural and functional asymmetry is exemplified from work done in our laboratory on auditory laterality using an empirical procedure called dichotic listening. This also involves different ways of validating the dichotic listening procedure against both invasive and non-invasive techniques, including PET and fMRI blood flow recordings. A major argument is that the human brain shows a substantial interaction between structurally, or "bottom-up" asymmetry and cognitively, or "top-down" modulation, through a focus of attention to the right or left side in auditory space. These results open up a more dynamic and interactive view of functional brain asymmetry than the traditional static view that the brain is lateralized, or asymmetric, only for specific stimuli and stimulus properties.

  6. Multiple aldehyde reductases of human brain.

    PubMed

    Hoffman, P L; Wermuth, B; von Wartburg, J P

    1980-01-01

    Human brain contains four forms of aldehyde reducing enzymes. One major activity, designated AR3, has properties indicating its identity with the NADPH-dependent aldehyde reductase, EC 1.1.1.2. The other major form of human brain enzyme, AR1, which is also NADPH-dependent, reduces both aldehyde and ketone-containing substrates, including vitamin K3 (menadione) and daunorubicin, a cancer chemotherapeutic agent. This enzyme is very sensitive to inhibition by the flavonoids quercitrin and quercetine, and may be analogous to a daunorubicin reductase previously described in liver of other species. One minor form of human brain aldehyde reductase, AR2, demonstrates substrate specificity and inhibitor sensitivity which suggest its similarity to aldose reductases found in lens and other tissues of many species. This enzyme, which can also use NADH as cofactor to some extent, is the most active in reducing the aldehyde derivatives of the biogenic amines. The fourth human brain enzyme ("SSA reductase") differs from the other forms in its ability to use NADH as well as or better than NADPH as cofactor, and in its molecular weight, which is nearly twice that of the other forms. It is quite specific for succinic semialdehyde (SSA) as substrate, and was found to be significantly inhibited only by quercetine and quercitrin. AR3 can also reduce SSA, and both enzymes may contribute to the production of gamma-hydroxybutyric acid in vivo. These results indicate that the human brain aldehyde reductases can play relatively specific physiologic roles. PMID:7424738

  7. Cytogenetics of human brain tumors

    SciTech Connect

    Finkernagel, S.W.; Kletz, T.; Day-Salvatore, D.L.

    1994-09-01

    Chromosome studies of 55 brain tumors, including meningiomas, gliomas, astrocyomas and pituatary adenomas, were performed. Primary and first passage cultures were successfully obtained in 75% of these samples with an average of 18 G-banded metaphases analyzed per tumor. 44% of all the brain tumors showed numerical and or structural abnormalities. 46% of the primary and 38% of the first passage cultures showed similar numerical gains/losses and complex karyotypic changes. The most frequent numerical abnormalities (n {ge} 5) included loss of chromosomes 10, 22, and Y. The structural abnormalities most often seen involved 1p, 2, 5, 7, 17q and 19. This is an ongoing study which will attempt to correlate tumor type with specific karyotypic changes and to see if any of the observed chromosomal abnormalities provide prognostic indicators.

  8. Transcriptional Landscape of the Prenatal Human Brain

    PubMed Central

    Miller, Jeremy A.; Ding, Song-Lin; Sunkin, Susan M.; Smith, Kimberly A; Ng, Lydia; Szafer, Aaron; Ebbert, Amanda; Riley, Zackery L.; Aiona, Kaylynn; Arnold, James M.; Bennet, Crissa; Bertagnolli, Darren; Brouner, Krissy; Butler, Stephanie; Caldejon, Shiella; Carey, Anita; Cuhaciyan, Christine; Dalley, Rachel A.; Dee, Nick; Dolbeare, Tim A.; Facer, Benjamin A. C.; Feng, David; Fliss, Tim P.; Gee, Garrett; Goldy, Jeff; Gourley, Lindsey; Gregor, Benjamin W.; Gu, Guangyu; Howard, Robert E.; Jochim, Jayson M.; Kuan, Chihchau L.; Lau, Christopher; Lee, Chang-Kyu; Lee, Felix; Lemon, Tracy A.; Lesnar, Phil; McMurray, Bergen; Mastan, Naveed; Mosqueda, Nerick F.; Naluai-Cecchini, Theresa; Ngo, Nhan-Kiet; Nyhus, Julie; Oldre, Aaron; Olson, Eric; Parente, Jody; Parker, Patrick D.; Parry, Sheana E.; Player, Allison Stevens; Pletikos, Mihovil; Reding, Melissa; Royall, Joshua J.; Roll, Kate; Sandman, David; Sarreal, Melaine; Shapouri, Sheila; Shapovalova, Nadiya V.; Shen, Elaine H.; Sjoquist, Nathan; Slaughterbeck, Clifford R.; Smith, Michael; Sodt, Andy J.; Williams, Derric; Zöllei, Lilla; Fischl, Bruce; Gerstein, Mark B.; Geschwind, Daniel H.; Glass, Ian A.; Hawrylycz, Michael J.; Hevner, Robert F.; Huang, Hao; Jones, Allan R.; Knowles, James A.; Levitt, Pat; Phillips, John W.; Sestan, Nenad; Wohnoutka, Paul; Dang, Chinh; Bernard, Amy; Hohmann, John G.; Lein, Ed S.

    2014-01-01

    Summary The anatomical and functional architecture of the human brain is largely determined by prenatal transcriptional processes. We describe an anatomically comprehensive atlas of mid-gestational human brain, including de novo reference atlases, in situ hybridization, ultra-high resolution magnetic resonance imaging (MRI) and microarray analysis on highly discrete laser microdissected brain regions. In developing cerebral cortex, transcriptional differences are found between different proliferative and postmitotic layers, wherein laminar signatures reflect cellular composition and developmental processes. Cytoarchitectural differences between human and mouse have molecular correlates, including species differences in gene expression in subplate, although surprisingly we find minimal differences between the inner and human-expanded outer subventricular zones. Both germinal and postmitotic cortical layers exhibit fronto-temporal gradients, with particular enrichment in frontal lobe. Finally, many neurodevelopmental disorder and human evolution-related genes show patterned expression, potentially underlying unique features of human cortical formation. These data provide a rich, freely-accessible resource for understanding human brain development. PMID:24695229

  9. A versatile new technique to clear mouse and human brain

    NASA Astrophysics Data System (ADS)

    Costantini, Irene; Di Giovanna, Antonino Paolo; Allegra Mascaro, Anna Letizia; Silvestri, Ludovico; Müllenbroich, Marie Caroline; Sacconi, Leonardo; Pavone, Francesco S.

    2015-07-01

    Large volumes imaging with microscopic resolution is limited by light scattering. In the last few years based on refractive index matching, different clearing approaches have been developed. Organic solvents and water-based optical clearing agents have been used for optical clearing of entire mouse brain. Although these methods guarantee high transparency and preservation of the fluorescence, though present other non-negligible limitations. Tissue transformation by CLARITY allows high transparency, whole brain immunolabelling and structural and molecular preservation. This method however requires a highly expensive refractive index matching solution limiting practical applicability. In this work we investigate the effectiveness of a water-soluble clearing agent, the 2,2'-thiodiethanol (TDE) to clear mouse and human brain. TDE does not quench the fluorescence signal, is compatible with immunostaining and does not introduce any deformation at sub-cellular level. The not viscous nature of the TDE make it a suitable agent to perform brain slicing during serial two-photon (STP) tomography. In fact, by improving penetration depth it reduces tissue slicing, decreasing the acquisition time and cutting artefacts. TDE can also be used as a refractive index medium for CLARITY. The potential of this method has been explored by imaging a whole transgenic mouse brain with the light sheet microscope. Moreover we apply this technique also on blocks of dysplastic human brain tissue transformed with CLARITY and labeled with different antibody. This clearing approach significantly expands the application of single and two-photon imaging, providing a new useful method for quantitative morphological analysis of structure in mouse and human brain.

  10. Interleukin-6 gene (IL-6): a possible role in brain morphology in the healthy adult brain

    PubMed Central

    2012-01-01

    Background Cytokines such as interleukin 6 (IL-6) have been implicated in dual functions in neuropsychiatric disorders. Little is known about the genetic predisposition to neurodegenerative and neuroproliferative properties of cytokine genes. In this study the potential dual role of several IL-6 polymorphisms in brain morphology is investigated. Methodology In a large sample of healthy individuals (N = 303), associations between genetic variants of IL-6 (rs1800795; rs1800796, rs2069833, rs2069840) and brain volume (gray matter volume) were analyzed using voxel-based morphometry (VBM). Selection of single nucleotide polymorphisms (SNPs) followed a tagging SNP approach (e.g., Stampa algorigthm), yielding a capture 97.08% of the variation in the IL-6 gene using four tagging SNPs. Principal findings/results In a whole-brain analysis, the polymorphism rs1800795 (−174 C/G) showed a strong main effect of genotype (43 CC vs. 150 CG vs. 100 GG; x = 24, y = −10, z = −15; F(2,286) = 8.54, puncorrected = 0.0002; pAlphaSim-corrected = 0.002; cluster size k = 577) within the right hippocampus head. Homozygous carriers of the G-allele had significantly larger hippocampus gray matter volumes compared to heterozygous subjects. None of the other investigated SNPs showed a significant association with grey matter volume in whole-brain analyses. Conclusions/significance These findings suggest a possible neuroprotective role of the G-allele of the SNP rs1800795 on hippocampal volumes. Studies on the role of this SNP in psychiatric populations and especially in those with an affected hippocampus (e.g., by maltreatment, stress) are warranted. PMID:22695063

  11. Seasonality in human cognitive brain responses.

    PubMed

    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. PMID:26858432

  12. Outer brain barriers in rat and human development

    PubMed Central

    Brøchner, Christian B.; Holst, Camilla B.; 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-conception) and adults using immunohistochemistry and confocal microscopy. Antibodies against claudin-11, BLBP, collagen 1, SSEA-4, MAP2, YKL-40, and its receptor IL-13Rα2 and EAAT1 were used to describe morphological characteristics and functional aspects of the outer brain barriers. Claudin-11 was a reliable marker of the arachnoid blood-CSF barrier. Collagen 1 delineated the subarachnoid space and stained pial surface layer. BLBP defined radial glial end feet layer and SSEA-4 and YKL-40 were present in both leptomeningeal cells and end feet layer, which transformed into glial limitans. IL-13Rα2 and EAAT1 were present in the end feet layer illustrating transporter/receptor presence in the outer CSF-brain barrier. MAP2 immunostaining in adult brain outlined the lower border of glia limitans; remnants of end feet were YKL-40 positive in some areas. We propose that outer brain barriers are composed of at least 3 interfaces: blood-CSF barrier across arachnoid barrier cell layer, blood-CSF barrier across pial microvessels, and outer CSF-brain barrier comprising glial end feet layer/pial surface layer. PMID:25852456

  13. Magnetic resonance spectroscopy of the human brain

    NASA Astrophysics Data System (ADS)

    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.

  14. Cholesterol metabolites exported from human brain.

    PubMed

    Iuliano, Luigi; Crick, Peter J; Zerbinati, Chiara; Tritapepe, Luigi; Abdel-Khalik, Jonas; Poirot, Marc; Wang, Yuqin; Griffiths, William J

    2015-07-01

    The human brain contains approximately 25% of the body's cholesterol. The brain is separated from the circulation by the blood brain barrier. While cholesterol will not passes this barrier, oxygenated forms of cholesterol can cross the barrier. Here by measuring the difference in the oxysterol content of blood plasma in the jugular vein and in a forearm vein by mass spectrometry (MS) we were able to determine the flux of more than 20 cholesterol metabolites between brain and the circulation. We confirm that 24S-hydroxycholesterol is exported from brain at a rate of about 2-3mg/24h. Gas chromatography (GC)-MS data shows that the cholesterol metabolites 5α-hydroxy-6-oxocholesterol (3β,5α-dihydroxycholestan-6-one), 7β-hydroxycholesterol and 7-oxocholesterol, generally considered to be formed through reactive oxygen species, are similarly exported from brain at rates of about 0.1, 2 and 2mg/24h, respectively. Although not to statistical significance both GC-MS and liquid chromatography (LC)-MS methods indicate that (25R)26-hydroxycholesterol is imported to brain, while LC-MS indicates that 7α-hydroxy-3-oxocholest-4-enoic acid is exported from brain. PMID:25668615

  15. Human midsagittal brain shape variation: patterns, allometry and integration

    PubMed Central

    Bruner, Emiliano; Martin-Loeches, Manuel; Colom, Roberto

    2010-01-01

    Midsagittal cerebral morphology provides a homologous geometrical reference for brain shape and cortical vs. subcortical spatial relationships. In this study, midsagittal brain shape variation is investigated in a sample of 102 humans, in order to describe and quantify the major patterns of correlation between morphological features, the effect of size and sex on general anatomy, and the degree of integration between different cortical and subcortical areas. The only evident pattern of covariation was associated with fronto-parietal cortical bulging. The allometric component was weak for the cortical profile, but more robust for the posterior subcortical areas. Apparent sex differences were evidenced in size but not in brain shape. Cortical and subcortical elements displayed scarcely integrated changes, suggesting a modular separation between these two areas. However, a certain correlation was found between posterior subcortical and parietal cortical variations. These results should be directly integrated with information ranging from functional craniology to wiring organization, and with hypotheses linking brain shape and the mechanical properties of neurons during morphogenesis. PMID:20345859

  16. Human midsagittal brain shape variation: patterns, allometry and integration.

    PubMed

    Bruner, Emiliano; Martin-Loeches, Manuel; Colom, Roberto

    2010-05-01

    Midsagittal cerebral morphology provides a homologous geometrical reference for brain shape and cortical vs. subcortical spatial relationships. In this study, midsagittal brain shape variation is investigated in a sample of 102 humans, in order to describe and quantify the major patterns of correlation between morphological features, the effect of size and sex on general anatomy, and the degree of integration between different cortical and subcortical areas. The only evident pattern of covariation was associated with fronto-parietal cortical bulging. The allometric component was weak for the cortical profile, but more robust for the posterior subcortical areas. Apparent sex differences were evidenced in size but not in brain shape. Cortical and subcortical elements displayed scarcely integrated changes, suggesting a modular separation between these two areas. However, a certain correlation was found between posterior subcortical and parietal cortical variations. These results should be directly integrated with information ranging from functional craniology to wiring organization, and with hypotheses linking brain shape and the mechanical properties of neurons during morphogenesis. PMID:20345859

  17. Human Maternal Brain Plasticity: Adaptation to Parenting.

    PubMed

    Kim, Pilyoung

    2016-09-01

    New mothers undergo dynamic neural changes that support positive adaptation to parenting and the development of mother-infant relationships. In this article, I review important psychological adaptations that mothers experience during pregnancy and the early postpartum period. I then review evidence of structural and functional plasticity in human mothers' brains, and explore how such plasticity supports mothers' psychological adaptation to parenting and sensitive maternal behaviors. Last, I discuss pregnancy and the early postpartum period as a window of vulnerabilities and opportunities when the human maternal brain is influenced by stress and psychopathology, but also receptive to interventions. PMID:27589497

  18. Revisiting Glycogen Content in the Human Brain.

    PubMed

    Öz, Gülin; DiNuzzo, Mauro; Kumar, Anjali; Moheet, Amir; Seaquist, Elizabeth R

    2015-12-01

    Glycogen provides an important glucose reservoir in the brain since the concentration of glucosyl units stored in glycogen is several fold higher than free glucose available in brain tissue. We have previously reported 3-4 µmol/g brain glycogen content using in vivo (13)C magnetic resonance spectroscopy (MRS) in conjunction with [1-(13)C]glucose administration in healthy humans, while higher levels were reported in the rodent brain. Due to the slow turnover of bulk brain glycogen in humans, complete turnover of the glycogen pool, estimated to take 3-5 days, was not observed in these prior studies. In an attempt to reach complete turnover and thereby steady state (13)C labeling in glycogen, here we administered [1-(13)C]glucose to healthy volunteers for 80 h. To eliminate any net glycogen synthesis during this period and thereby achieve an accurate estimate of glycogen concentration, volunteers were maintained at euglycemic blood glucose levels during [1-(13)C]glucose administration and (13)C-glycogen levels in the occipital lobe were measured by (13)C MRS approximately every 12 h. Finally, we fitted the data with a biophysical model that was recently developed to take into account the tiered structure of the glycogen molecule and additionally incorporated blood glucose levels and isotopic enrichments as input function in the model. We obtained excellent fits of the model to the (13)C-glycogen data, and glycogen content in the healthy human brain tissue was found to be 7.8 ± 0.3 µmol/g, a value substantially higher than previous estimates of glycogen content in the human brain. PMID:26202425

  19. Human intelligence and brain networks

    PubMed Central

    Colom, Roberto; Karama, Sherif; Jung, Rex E.; Haier, Richard J.

    2010-01-01

    Intelligence can be defined as a general mental ability for reasoning, problem solving, and learning. Because of its general nature, intelligence integrates cognitive functions such as perception, attention, memory, language, or planning. On the basis of this definition, intelligence can be reliably measured by standardized tests with obtained scores predicting several broad social outcomes such as educational achievement, job performance, health, and longevity. A detailed understanding of the brain mechanisms underlying this general mental ability could provide significant individual and societal benefits. Structural and functional neuroimaging studies have generally supported a frontoparietal network relevant for intelligence. This same network has also been found to underlie cognitive functions related to perception, short-term memory storage, and language. The distributed nature of this network and its involvement in a wide range of cognitive functions fits well with the integrative nature of intelligence. A new key phase of research is beginning to investigate how functional networks relate to structural networks, with emphasis on how distributed brain areas communicate with each other. PMID:21319494

  20. Human astrocytes develop physiological morphology and remain quiescent in a novel 3D matrix.

    PubMed

    Placone, Amanda L; McGuiggan, Patricia M; Bergles, Dwight E; Guerrero-Cazares, Hugo; Quiñones-Hinojosa, Alfredo; Searson, Peter C

    2015-02-01

    Astrocytes are the most abundant glial cells in the brain and are responsible for diverse functions, from modulating synapse function to regulating the blood-brain barrier. In vivo, these cells exhibit a star-shaped morphology with multiple radial processes that contact synapses and completely surround brain capillaries. In response to trauma or CNS disease, astrocytes become activated, a state associated with profound changes in gene expression, including upregulation of intermediate filament proteins, such as glial fibrillary acidic protein (GFAP). The inability to recapitulate the complex structure of astrocytes and maintain their quiescent state in vitro is a major roadblock to further developments in tissue engineering and regenerative medicine. Here, we characterize astrocyte morphology and activation in various hydrogels to assess the feasibility of developing a matrix that mimics key aspects of the native microenvironment. We show that astrocytes seeded in optimized matrix composed of collagen, hyaluronic acid, and matrigel exhibit a star-shaped morphology with radial processes and do not upregulate GFAP expression, hallmarks of quiescent astrocytes in the brain. In these optimized gels, collagen I provides structural support, HA mimics the brain extracellular matrix, and matrigel provides endothelial cell compatibility and was found to minimize GFAP upregulation. This defined 3D microenvironment for maintaining human astrocytes in vitro provides new opportunities for developing improved models of the blood-brain barrier and studying their response to stress signals. PMID:25542801

  1. Changes in brain morphology in albinism reflect reduced visual acuity.

    PubMed

    Bridge, Holly; von dem Hagen, Elisabeth A H; Davies, George; Chambers, Claire; Gouws, Andre; Hoffmann, Michael; Morland, Antony B

    2014-07-01

    Albinism, in humans and many animal species, has a major impact on the visual system, leading to reduced acuity, lack of binocular function and nystagmus. In addition to the lack of a foveal pit, there is a disruption to the routing of the nerve fibers crossing at the optic chiasm, resulting in excessive crossing of fibers to the contralateral hemisphere. However, very little is known about the effect of this misrouting on the structure of the post-chiasmatic visual pathway, and the occipital lobes in particular. Whole-brain analyses of cortical thickness in a large cohort of subjects with albinism showed an increase in cortical thickness, relative to control subjects, particularly in posterior V1, corresponding to the foveal representation. Furthermore, mean cortical thickness across entire V1 was significantly greater in these subjects compared to controls and negatively correlated with visual acuity in albinism. Additionally, the group with albinism showed decreased gyrification in the left ventral occipital lobe. While the increase in cortical thickness in V1, also found in congenitally blind subjects, has been interpreted to reflect a lack of pruning, the decreased gyrification in the ventral extrastriate cortex may reflect the reduced input to the foveal regions of the ventral visual stream. PMID:23039995

  2. Comparative brain morphology of Neotropical parrots (Aves, Psittaciformes) inferred from virtual 3D endocasts.

    PubMed

    Carril, Julieta; Tambussi, Claudia Patricia; Degrange, Federico Javier; Benitez Saldivar, María Juliana; Picasso, Mariana Beatriz Julieta

    2016-08-01

    Psittaciformes are a very diverse group of non-passerine birds, with advanced cognitive abilities and highly developed locomotor and feeding behaviours. Using computed tomography and three-dimensional (3D) visualization software, the endocasts of 14 extant Neotropical parrots were reconstructed, with the aim of analysing, comparing and exploring the morphology of the brain within the clade. A 3D geomorphometric analysis was performed, and the encephalization quotient (EQ) was calculated. Brain morphology character states were traced onto a Psittaciformes tree in order to facilitate interpretation of morphological traits in a phylogenetic context. Our results indicate that: (i) there are two conspicuously distinct brain morphologies, one considered walnut type (quadrangular and wider than long) and the other rounded (narrower and rostrally tapered); (ii) Psittaciformes possess a noticeable notch between hemisphaeria that divides the bulbus olfactorius; (iii) the plesiomorphic and most frequently observed characteristics of Neotropical parrots are a rostrally tapered telencephalon in dorsal view, distinctly enlarged dorsal expansion of the eminentia sagittalis and conspicuous fissura mediana; (iv) there is a positive correlation between body mass and brain volume; (v) psittacids are characterized by high EQ values that suggest high brain volumes in relation to their body masses; and (vi) the endocranial morphology of the Psittaciformes as a whole is distinctive relative to other birds. This new knowledge of brain morphology offers much potential for further insight in paleoneurological, phylogenetic and evolutionary studies. PMID:26053196

  3. 'What' and 'where' in the human brain.

    PubMed

    Ungerleider, L G; Haxby, J V

    1994-04-01

    Multiple visual areas in the cortex of nonhuman primates are organized into two hierarchically organized and functionally specialized processing pathways, a 'ventral stream' for object vision and a 'dorsal stream' for spatial vision. Recent findings from positron emission tomography activation studies have localized these pathways within the human brain, yielding insights into cortical hierarchies, specialization of function, and attentional mechanisms. PMID:8038571

  4. CARBOXYHEMOGLOBIN AND BRAIN BLOOD FLOW IN HUMANS

    EPA Science Inventory

    It has been shown that with increased carboxyhemoglobin (COHb) and associated decrease in blood oxygen-carrying capacity, a compensatory increase in brain-blood flow (BBF) develops. he BBF response in humans has been shown to be quite variable. wo experiments were conducted in wh...

  5. Water diffusion reveals networks that modulate multiregional morphological plasticity after repetitive brain stimulation

    PubMed Central

    Abe, Mitsunari; Fukuyama, Hidenao; Mima, Tatsuya

    2014-01-01

    Repetitive brain stimulation protocols induce plasticity in the stimulated site in brain slice models. Recent evidence from network models has indicated that additional plasticity-related changes occur in nonstimulated remote regions. Despite increasing use of brain stimulation protocols in experimental and clinical settings, the neural substrates underlying the additional effects in remote regions are unknown. Diffusion-weighted MRI (DWI) probes water diffusion and can be used to estimate morphological changes in cortical tissue that occur with the induction of plasticity. Using DWI techniques, we estimated morphological changes induced by application of repetitive transcranial magnetic stimulation (rTMS) over the left primary motor cortex (M1). We found that rTMS altered water diffusion in multiple regions including the left M1. Notably, the change in water diffusion was retained longest in the left M1 and remote regions that had a correlation of baseline fluctuations in water diffusion before rTMS. We conclude that synchronization of water diffusion at rest between stimulated and remote regions ensures retention of rTMS-induced changes in water diffusion in remote regions. Synchronized fluctuations in the morphology of cortical microstructures between stimulated and remote regions might identify networks that allow retention of plasticity-related morphological changes in multiple regions after brain stimulation protocols. These results increase our understanding of the effects of brain stimulation-induced plasticity on multiregional brain networks. DWI techniques could provide a tool to evaluate treatment effects of brain stimulation protocols in patients with brain disorders. PMID:24619090

  6. Zika virus impairs growth in human neurospheres and brain organoids.

    PubMed

    Garcez, Patricia P; Loiola, Erick Correia; Madeiro da Costa, Rodrigo; Higa, Luiza M; Trindade, Pablo; Delvecchio, Rodrigo; Nascimento, Juliana Minardi; Brindeiro, Rodrigo; Tanuri, Amilcar; Rehen, Stevens K

    2016-05-13

    Since the emergence of Zika virus (ZIKV), reports of microcephaly have increased considerably in Brazil; however, causality between the viral epidemic and malformations in fetal brains needs further confirmation. We examined the effects of ZIKV infection in human neural stem cells growing as neurospheres and brain organoids. Using immunocytochemistry and electron microscopy, we showed that ZIKV targets human brain cells, reducing their viability and growth as neurospheres and brain organoids. These results suggest that ZIKV abrogates neurogenesis during human brain development. PMID:27064148

  7. Epilepsy: Extreme Events in the Human Brain

    NASA Astrophysics Data System (ADS)

    Lehnertz, Klaus

    The analysis of Xevents arising in dynamical systems with many degrees of freedom represents a challenge for many scientific fields. This is especially true for the open, dissipative, and adaptive system known as the human brain. Due to its complex structure, its immense functionality, and — as in the case of epilepsy — due to the coexistence of normal and abnormal functions, the brain can be regarded as one of the most complex and fascinating systems in nature. Data gathered so far show that the epileptic process exhibits a high spatial and temporal variability. Small, specific, regions of the brain are responsible for the generation of focal epileptic seizures, and the amount of time a patient spends actually having seizures is only a small fraction of his/her lifetime. In between these Xevents large parts of the brain exhibit normal functioning. Since the occurrence of seizures usually can not be explained by exogenous factors, and since the brain recovers its normal state after a seizure in the majority of cases, this might indicate that endogenous nonlinear (deterministic and/or stochastic) properties are involved in the control of these Xevents. In fact, converging evidence now indicates that (particularly) nonlinear approaches to the analysis of brain activity allow us to define precursors which, provided sufficient sensitivity and specificity can be obtained, might lead to the development of patient-specific seizure anticipation and seizure prevention strategies.

  8. Methylomic trajectories across human fetal brain development.

    PubMed

    Spiers, Helen; Hannon, Eilis; Schalkwyk, Leonard C; Smith, Rebecca; Wong, Chloe C Y; O'Donovan, Michael C; Bray, Nicholas J; Mill, Jonathan

    2015-03-01

    Epigenetic processes play a key role in orchestrating transcriptional regulation during development. The importance of DNA methylation in fetal brain development is highlighted by the dynamic expression of de novo DNA methyltransferases during the perinatal period and neurodevelopmental deficits associated with mutations in the methyl-CpG binding protein 2 (MECP2) gene. However, our knowledge about the temporal changes to the epigenome during fetal brain development has, to date, been limited. We quantified genome-wide patterns of DNA methylation at ∼ 400,000 sites in 179 human fetal brain samples (100 male, 79 female) spanning 23 to 184 d post-conception. We identified highly significant changes in DNA methylation across fetal brain development at >7% of sites, with an enrichment of loci becoming hypomethylated with fetal age. Sites associated with developmental changes in DNA methylation during fetal brain development were significantly underrepresented in promoter regulatory regions but significantly overrepresented in regions flanking CpG islands (shores and shelves) and gene bodies. Highly significant differences in DNA methylation were observed between males and females at a number of autosomal sites, with a small number of regions showing sex-specific DNA methylation trajectories across brain development. Weighted gene comethylation network analysis (WGCNA) revealed discrete modules of comethylated loci associated with fetal age that are significantly enriched for genes involved in neurodevelopmental processes. This is, to our knowledge, the most extensive study of DNA methylation across human fetal brain development to date, confirming the prenatal period as a time of considerable epigenomic plasticity. PMID:25650246

  9. The Human Brain Project and neuromorphic computing

    PubMed Central

    Calimera, Andrea; Macii, Enrico; Poncino, Massimo

    Summary Understanding how the brain manages billions of processing units connected via kilometers of fibers and trillions of synapses, while consuming a few tens of Watts could provide the key to a completely new category of hardware (neuromorphic computing systems). In order to achieve this, a paradigm shift for computing as a whole is needed, which will see it moving away from current “bit precise” computing models and towards new techniques that exploit the stochastic behavior of simple, reliable, very fast, low-power computing devices embedded in intensely recursive architectures. In this paper we summarize how these objectives will be pursued in the Human Brain Project. PMID:24139655

  10. Human freedom and the brain.

    PubMed

    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. PMID:25384854

  11. Excitotoxic neuronal death in the immature brain is an apoptosis-necrosis morphological continuum.

    PubMed

    Portera-Cailliau, C; Price, D L; Martin, L J

    1997-02-01

    Glutamate-induced excitotoxicity is a clinically relevant degenerative process that causes selective neuronal death by mechanisms that remain unclear. Cell death is usually classified as apoptotic or necrotic based on biochemical and morphological criteria. Excitotoxic lesions in the adult rat striatum result in neuronal death associated with apoptotic DNA laddering despite a necrotic appearance of neurons ultrastructurally. This suggests that apoptosis and necrosis may not be mutually exclusive modes of cell death. Here, we characterized normal developmental cell death in the newborn rat brain with respect to DNA fragmentation patterns and ultrastructural morphology to establish a standard for apoptosis in the nervous system, and we concluded that it is essentially indistinguishable from apoptosis described in other tissues. We then investigated whether brain maturity could influence the morphology of neuronal death in vivo in the excitotoxically lesioned newborn rat forebrain. Kainic acid induced DNA laddering and death of neurons exhibiting a variety of morphologies, ranging from necrosis to apoptosis. In neurons that were dying by apoptosis, morphologic changes were characterized by a highly ordered sequence of organelle abnormalities, with swelling of endoplasmic reticulum and Golgi vesiculation preceding most nuclear changes and mitochondrial disruption. We concluded that brain maturity influences the morphologic phenotype of neurodegeneration and that excitotoxic neuronal death in the immature brain is not a uniform event but, rather, a continuum of apoptotic, necrotic, and overlapping morphologies. This excitotoxic paradigm might prove useful for analyzing the mechanisms that govern cell death under physiological and pathological conditions. PMID:9120055

  12. Infrasounds and biorhythms of the human brain

    NASA Astrophysics Data System (ADS)

    Panuszka, Ryszard; Damijan, Zbigniew; Kasprzak, Cezary; McGlothlin, James

    2002-05-01

    Low Frequency Noise (LFN) and infrasound has begun a new public health hazard. Evaluations of annoyance of (LFN) on human occupational health were based on standards where reactions of human auditory system and vibrations of parts of human body were small. Significant sensitivity has been observed on the central nervous system from infrasonic waves especially below 10 Hz. Observed follow-up effects in the brain gives incentive to study the relationship between parameters of waves and reactions obtained of biorhythms (EEG) and heart action (EKG). New results show the impact of LFN on the electrical potentials of the brain are dependent on the pressure waves on the human body. Electrical activity of circulatory system was also affected. Signals recorded in industrial workplaces were duplicated by loudspeakers and used to record data from a typical LFN spectra with 5 and 7 Hz in a laboratory chamber. External noise, electromagnetic fields, temperature, dust, and other elements were controlled. Results show not only a follow-up effect in the brain but also a result similar to arrhythmia in the heart. Relaxations effects were observed of people impacted by waves generated from natural sources such as streams and waterfalls.

  13. Molecular genetic determinants of human brain size.

    PubMed

    Tang, Bor Luen

    2006-07-01

    Cognitive skills such as tool use, syntactical languages, and self-awareness differentiate humans from other primates. The underlying basis for this cognitive difference has been widely associated with a high encephalization quotient and an anatomically distinct, exceptionally large cerebral cortex. Investigations on congenital microcephaly had revealed several genes that affect mammalian brain size when mutated. At least four of these, microcephalin (MCPH1), abnormal spindle-like microcephaly-associated (ASPM), cyclin-dependent kinase 5 regulatory associated protein 2 (CDK5RAP2), and centromere-associated protein J (CENPJ) are known to have undergone significant positive selection in the great apes and human lineages during primate evolution. MCPH1 and ASPM both have very young single nucleotide polymorphism haplotypes associated with modern humans, and these genes are presumably still evolving in Homo sapiens. Microcephalin has a role in DNA damage response and regulation of cell cycle checkpoints. The other known microcephaly-associated genes encode microtubule-associated centrosomal proteins that might regulate neural progenitor cell division and cell number. Recent reports have also unveiled a previously unknown function of ephrins and Eph in the regulation of neural progenitor cell death with a consequential effect on brain size. Understanding the mechanism for developmental control of brain organogenesis by these genes, and others such as FOXP2, shall provide fresh perspectives on the evolution of human intelligence. PMID:16716254

  14. Processing verbal morphology in patients with congenital left-hemispheric brain lesions.

    PubMed

    Knecht, Marion; Lidzba, Karen

    2016-01-01

    The goal of this study was to test whether children, teenagers and adults with congenital left-hemispheric brain lesions master the regularities of German verbal inflectional morphology. Thirteen patients and 35 controls without brain damage participated in three experiments. A grammaticality judgment task, a participle inflection task and a nonce-verb inflection task revealed significant differences between patients and controls. In addition, a main effect of verb type could be observed as patients and controls made more mistakes with irregular than with regular verbs. The findings indicate that the congenitally damaged brain not only has difficulties with complex syntactic structures during language development, as reported by earlier studies, but also has persistent deficits on the morphological level. These observations suggest that the plasticity of the developing brain cannot fully compensate for congenital brain damage which affects regions associated with language functions. PMID:27156034

  15. Human brain disease recreated in mice

    SciTech Connect

    Marx, J.

    1990-12-14

    In the early 1980s, neurologist Stanley Prusiner suggested that scrapie, an apparently infectious degenerative brain disease of sheep, could be transmitted by prions, infectious particles made just of protein - and containing no nucleic acids. But prion research has come a long way since then. In 1985, the cloning of the gene encoding the prion protein proved that it does in fact exist. And the gene turned out to be widely expressed in the brains of higher organisms, a result suggesting that the prion protein has a normal brain function that can somehow be subverted, leading to brain degeneration. Then studies done during the past 2 years suggested that specific mutations in the prion gene might cause two similar human brain diseases, Gerstmann-Straeussler-Scheinker syndrome (GSS) and Creutzfelt-Jakob disease. Now, Prusiner's group at the University of California, San Francisco, has used genetic engineering techniques to recreate GSS by transplanting the mutated prion gene into mice. Not only will the animal model help neurobiologists answer the many remaining questions about prions and how they work, but it may also shed some light on other neurodegenerative diseases as well.

  16. Evolving networks in the human epileptic brain

    NASA Astrophysics Data System (ADS)

    Lehnertz, Klaus; Ansmann, Gerrit; Bialonski, Stephan; Dickten, Henning; Geier, Christian; Porz, Stephan

    2014-01-01

    Network theory provides novel concepts that promise an improved characterization of interacting dynamical systems. Within this framework, evolving networks can be considered as being composed of nodes, representing systems, and of time-varying edges, representing interactions between these systems. This approach is highly attractive to further our understanding of the physiological and pathophysiological dynamics in human brain networks. Indeed, there is growing evidence that the epileptic process can be regarded as a large-scale network phenomenon. We here review methodologies for inferring networks from empirical time series and for a characterization of these evolving networks. We summarize recent findings derived from studies that investigate human epileptic brain networks evolving on timescales ranging from few seconds to weeks. We point to possible pitfalls and open issues, and discuss future perspectives.

  17. Interactive brain atlas with the Visible Human Project data: development methods and techniques.

    PubMed

    Toh, M Y; Falk, R B; Main, J S

    1996-09-01

    A prototype of an interactive digital brain atlas was developed by using the Visible Human Project data set of the National Library of Medicine. This data set provides corresponding axial magnetic resonance images, computed tomographic images, and cryosections of the brain. The prototype was developed to demonstrate the techniques and methods that will be used throughout the development process of the atlas. The atlas has a graphical user interface, supports user interaction with various representations of the brain (i.e., two-dimensional and three-dimensional [3D]), and displays multiple images simultaneously. Motion sequences of the 3D brain were incorporated in the atlas to provide an important link between two-dimensional brain slices and volume-rendered 3D anatomic structures. Volume visualization tools were used to interactively render, rotate, and reslice the volumetric brain data. The brain was segmented with manual tracing, thresholding, and morphologic algorithms and then rendered with volume-rendering tools. PMID:8888399

  18. Imaging Monoamine Oxidase in the Human Brain

    SciTech Connect

    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.

  19. Phenotypic integration of brain size and head morphology in Lake Tanganyika Cichlids

    PubMed Central

    2014-01-01

    Background Phenotypic integration among different anatomical parts of the head is a common phenomenon across vertebrates. Interestingly, despite centuries of research into the factors that contribute to the existing variation in brain size among vertebrates, little is known about the role of phenotypic integration in brain size diversification. Here we used geometric morphometrics on the morphologically diverse Tanganyikan cichlids to investigate phenotypic integration across key morphological aspects of the head. Then, while taking the effect of shared ancestry into account, we tested if head shape was associated with brain size while controlling for the potentially confounding effect of feeding strategy. Results The shapes of the anterior and posterior parts of the head were strongly correlated, indicating that the head represents an integrated morphological unit in Lake Tanganyika cichlids. After controlling for phylogenetic non-independence, we also found evolutionary associations between head shape, brain size and feeding ecology. Conclusions Geometric morphometrics and phylogenetic comparative analyses revealed that the anterior and posterior parts of the head are integrated, and that head morphology is associated with brain size and feeding ecology in Tanganyikan cichlid fishes. In light of previous results on mammals, our results suggest that the influence of phenotypic integration on brain diversification is a general process. PMID:24593160

  20. Ascorbic acid in fetal human brain

    PubMed Central

    Adlard, B. P. F.; De Souza, S. W.; Moon, Susan

    1974-01-01

    Ascorbic acid concentrations in fetal human forebrain in the period 11 to 19 weeks' gestational age were 4 to 11 times higher than those of adults. Levels fell progressively with increasing gestational age but, in term babies dying within 4 weeks of birth, were still at least 3 times those of adults. It was confirmed that, in women delivering at term, ascorbic acid concentrations are approximately 4 times higher in cord blood plasma than in maternal blood plasma. The possible importance of ascorbic acid for normal human brain development is discussed. PMID:4830116

  1. Tracking Hierarchical Processing in Morphological Decomposition with Brain Potentials

    ERIC Educational Resources Information Center

    Lavric, Aureliu; Elchlepp, Heike; Rastle, Kathleen

    2012-01-01

    One important debate in psycholinguistics concerns the nature of morphological decomposition processes in visual word recognition (e.g., darkness = {dark} + {-ness}). One theory claims that these processes arise during orthographic analysis and prior to accessing meaning (Rastle & Davis, 2008), and another argues that these processes arise through…

  2. MRI and MRS of human brain tumors.

    PubMed

    Hou, Bob L; Hu, Jiani

    2009-01-01

    The purpose of this chapter is to provide an introduction to magnetic resonance imaging (MRI) and magnetic resonance spectroscopy (MRS) of human brain tumors, including the primary applications and basic terminology involved. Readers who wish to know more about this broad subject should seek out the referenced books (1. Tofts (2003) Quantitative MRI of the brain. Measuring changes caused by disease. Wiley; Bradley and Stark (1999) 2. Magnetic resonance imaging, 3rd Edition. Mosby Inc; Brown and Semelka (2003) 3. MRI basic principles and applications, 3rd Edition. Wiley-Liss) or reviews (4. Top Magn Reson Imaging 17:127-36, 2006; 5. JMRI 24:709-724, 2006; 6. Am J Neuroradiol 27:1404-1411, 2006).MRI is the most popular means of diagnosing human brain tumors. The inherent difference in the magnetic resonance (MR) properties of water between normal tissues and tumors results in contrast differences on the image that provide the basis for distinguishing tumors from normal tissues. In contrast to MRI, which provides spatial maps or images using water signals of the tissues, proton MRS detects signals of tissue metabolites. MRS can complement MRI because the observed MRS peaks can be linked to inherent differences in biochemical profiles between normal tissues and tumors.The goal of MRI and MRS is to characterize brain tumors, including tumor core, edge, edema, volume, types, and grade. The commonly used brain tumor MRI protocol includes T2-weighted images and T1-weighted images taken both before and after the injection of a contrast agent (typically gadolinium: Gd). The commonly used MRS technique is either point-resolved spectroscopy (PRESS) or stimulated echo acquisition mode (STEAM). PMID:19381963

  3. Toward Developmental Connectomics of the Human Brain.

    PubMed

    Cao, Miao; Huang, Hao; Peng, Yun; Dong, Qi; He, Yong

    2016-01-01

    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 developmental

  4. Toward Developmental Connectomics of the Human Brain

    PubMed Central

    Cao, Miao; Huang, Hao; Peng, Yun; Dong, Qi; He, Yong

    2016-01-01

    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 developmental

  5. Morphological asymmetries of mouse brain assessed by geometric morphometric analysis of MRI data.

    PubMed

    Barbeito-Andrés, Jimena; Bernal, Valeria; Gonzalez, Paula N

    2016-09-01

    Mammalian brain has repeated structures at both sides of the median plane, although some asymmetries have been described even under normal conditions. Characterizing normal patterns of asymmetry in mouse brain is important to recognize features that depart from expected ranges in the most widely used mammalian model. Analyses on brain morphology based on magnetic resonance image (MRI) have largely focused on volumes while less is known about shape asymmetry. We introduce a flexible protocol based on geometric morphometrics to assess patterns of asymmetry in shape and size of mouse brain from microMRI scans. After systematic digitization of landmarks and semilandmarks, we combine multivariate methods for statistical analyses with visualization tools to display the results. No preliminary treatment of the images (e.g. space normalization) is needed to collect data on MRI slices and visual representations improve the interpretation of the results. Results indicated that the protocol is highly repeatable. Asymmetry was more evident for shape than for size. Particularly, fluctuating asymmetry accounted for more variation than directional asymmetry in all brain regions. Since this approach can detect subtle shape variation between sides, it is a promising methodology to explore morphological changes in the brain of model organisms and can be applied in future studies addressing the effect of genetic and environmental factors on brain morphology. PMID:27108357

  6. Brain structures in the sciences and humanities.

    PubMed

    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). PMID:25079346

  7. Restraint Stress-Induced Morphological Changes at the Blood-Brain Barrier in Adult Rats

    PubMed Central

    Sántha, Petra; Veszelka, Szilvia; Hoyk, Zsófia; Mészáros, Mária; Walter, Fruzsina R.; Tóth, Andrea E.; Kiss, Lóránd; Kincses, András; Oláh, Zita; Seprényi, György; Rákhely, Gábor; Dér, András; Pákáski, Magdolna; Kálmán, János; Kittel, Ágnes; Deli, Mária A.

    2016-01-01

    Stress is well-known to contribute to the development of both neurological and psychiatric diseases. While the role of the blood-brain barrier is increasingly recognized in the development of neurodegenerative disorders, such as Alzheimer's disease, dysfunction of the blood-brain barrier has been linked to stress-related psychiatric diseases only recently. In the present study the effects of restraint stress with different duration (1, 3, and 21 days) were investigated on the morphology of the blood-brain barrier in male adult Wistar rats. Frontal cortex and hippocampus sections were immunostained for markers of brain endothelial cells (claudin-5, occluding, and glucose transporter-1) and astroglia (GFAP). Staining pattern and intensity were visualized by confocal microscopy and evaluated by several types of image analysis. The ultrastructure of brain capillaries was investigated by electron microscopy. Morphological changes and intensity alterations in brain endothelial tight junction proteins claudin-5 and occludin were induced by stress. Following restraint stress significant increases in the fluorescence intensity of glucose transporter-1 were detected in brain endothelial cells in the frontal cortex and hippocampus. Significant reductions in GFAP fluorescence intensity were observed in the frontal cortex in all stress groups. As observed by electron microscopy, 1-day acute stress induced morphological changes indicating damage in capillary endothelial cells in both brain regions. After 21 days of stress thicker and irregular capillary basal membranes in the hippocampus and edema in astrocytes in both regions were seen. These findings indicate that stress exerts time-dependent changes in the staining pattern of tight junction proteins occludin, claudin-5, and glucose transporter-1 at the level of brain capillaries and in the ultrastructure of brain endothelial cells and astroglial endfeet, which may contribute to neurodegenerative processes, cognitive and

  8. Immunohistochemical demonstration of specific antigens in the human brain fixed in zinc-ethanol-formaldehyde.

    PubMed

    Korzhevskii, D E; Sukhorukova, E G; Kirik, O V; Grigorev, I P

    2015-01-01

    Tissue fixation is critical for immunohistochemistry. Recently, we developed a zinc-ethanol-formalin fixative (ZEF), and the present study was aimed to assess the applicability of the ZEF for the human brain histology and immunohistochemistry and to evaluate the detectability of different antigens in the human brain fixed with ZEF. In total, 11 antigens were tested, including NeuN, neuron-specific enolase, GFAP, Iba-1, calbindin, calretinin, choline acetyltransferase, glutamic acid decarboxylase (GAD65), tyrosine hydroxylase, synaptophysin, and α-tubulin. The obtained data show that: i) the ZEF has potential for use in general histological practice, where detailed characterization of human brain morphology is needed; ii) the antigens tested are well-preserved in the human brain specimens fixed in the ZEF. PMID:26428887

  9. Perfusion harmonic imaging of the human brain

    NASA Astrophysics Data System (ADS)

    Metzler, Volker H.; Seidel, Guenter; Wiesmann, Martin; Meyer, Karsten; Aach, Til

    2003-05-01

    The fast visualisation of cerebral microcirculation supports diagnosis of acute cerebrovascular diseases. However, the commonly used CT/MRI-based methods are time consuming and, moreover, costly. Therefore we propose an alternative approach to brain perfusion imaging by means of ultrasonography. In spite of the low signal/noise-ratio of transcranial ultrasound and the high impedance of the skull, flow images of cerebral blood flow can be derived by capturing the kinetics of appropriate contrast agents by harmonic ultrasound image sequences. In this paper we propose three different methods for human brain perfusion imaging, each of which yielding flow images indicating the status of the patient's cerebral microcirculation by visualising local flow parameters. Bolus harmonic imaging (BHI) displays the flow kinetics of bolus injections, while replenishment (RHI) and diminution harmonic imaging (DHI) compute flow characteristics from contrast agent continuous infusions. RHI measures the contrast agents kinetics in the influx phase and DHI displays the diminution kinetics of the contrast agent acquired from the decay phase. In clinical studies, BHI- and RHI-parameter images were found to represent comprehensive and reproducible distributions of physiological cerebral blood flow. For DHI it is shown, that bubble destruction and hence perfusion phenomena principally can be displayed. Generally, perfusion harmonic imaging enables reliable and fast bedside imaging of human brain perfusion. Due to its cost efficiency it complements cerebrovascular diagnostics by established CT/MRI-based methods.

  10. Morphological features of the neonatal brain support development of subsequent cognitive, language, and motor abilities

    PubMed Central

    Spann, Marisa N.; Bansal, Ravi; Rosen, Tove S.; Peterson, Bradley S.

    2014-01-01

    Knowledge of the role of brain maturation in the development of cognitive abilities derives primarily from studies of school-age children to adults. Little is known about the morphological features of the neonatal brain that support the subsequent development of abilities in early childhood, when maturation of the brain and these abilities are the most dynamic. The goal of our study was to determine whether brain morphology during the neonatal period supports early cognitive development through two years of age. We correlated morphological features of the cerebral surface assessed using deformation-based measures (surface distances) of high-resolution MRI scans for 33 healthy neonates, scanned between the first to sixth week of postmenstrual life, with subsequent measures of their motor, language, and cognitive abilities at ages 6, 12, 18, and 24 months. We found that morphological features of the cerebral surface of the frontal, mesial prefrontal, temporal, and occipital regions correlated with subsequent motor scores, posterior parietal regions correlated with subsequent language scores, and temporal and occipital regions correlated with subsequent cognitive scores. Measures of the anterior and middle portions of the cingulate gyrus correlated with scores across all three domains of ability. Most of the significant findings were inverse correlations located bilaterally in the brain. The inverse correlations may suggest either that a more protracted morphological maturation or smaller local volumes of neonatal brain tissue supports better performance on measures of subsequent motor, language, and cognitive abilities throughout the first two years of postnatal life. The correlations of morphological measures of the cingulate with measures of performance across all domains of ability suggest that the cingulate supports a broad range of skills in infancy and early childhood, similar to its functions in older children and adults. PMID:24615961

  11. Visualization of monoamine oxidase in human brain

    SciTech Connect

    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.

  12. Alterations induced by gestational stress in brain morphology and behaviour of the offspring.

    PubMed

    Weinstock, M

    2001-12-01

    Retrospective studies in humans suggest that chronic maternal stress during pregnancy, associated with raised plasma levels of CRH, ACTH and cortisol may increase the likelihood of preterm birth, developmental delays and behavioural abnormalities in the children. In adulthood, it may contribute to the significant association between the incidence of schizophrenia, increased left or mixed handedness, reduction in cerebral asymmetry and anomalies in brain morphology. Our studies and others have shown that prenatal stress in rats can mimic these developmental and behavioural alterations. These rats show a reduced propensity for social interaction, increased anxiety in intimidating or novel situations and a reduction in cerebral asymmetry and dopamine turnover, consistent with those in schizophrenic humans. Prenatally-stressed (PS) rats also show behaviour consistent with depression, including a phase-shift in their circadian rhythm for corticosterone, sleep abnormalities, a hedonic deficit and greater acquisition of learned helplessness under appropriate conditions. These behavioural abnormalities are associated with impaired regulation of the hypothalamic-pituitary-adrenal axis response to stress and increased CRH activity. PS males may show demasculinisation and feminisation of their sexual behaviour. The developmental and behavioural abnormalities in PS offspring could occur through sensitisation of the foetal brain by maternal stress hormones to the action of glucocorticoid and CRH and to neurotransmitters affected by them. This may have long-lasting consequences and could explain the precipitation of depressive symptoms or schizophrenia by psychosocial stress in later life. The character of the behavioural abnormalities probably depends on the timing of the maternal stress in relation to development of the particular neuronal systems. PMID:11689280

  13. A stereotaxic, population-averaged T1w ovine brain atlas including cerebral morphology and tissue volumes.

    PubMed

    Nitzsche, Björn; Frey, Stephen; Collins, Louis D; Seeger, Johannes; Lobsien, Donald; Dreyer, Antje; Kirsten, Holger; Stoffel, Michael H; Fonov, Vladimir S; Boltze, Johannes

    2015-01-01

    Standard stereotaxic reference systems play a key role in human brain studies. Stereotaxic coordinate systems have also been developed for experimental animals including non-human primates, dogs, and rodents. However, they are lacking for other species being relevant in experimental neuroscience including sheep. Here, we present a spatial, unbiased ovine brain template with tissue probability maps (TPM) that offer a detailed stereotaxic reference frame for anatomical features and localization of brain areas, thereby enabling inter-individual and cross-study comparability. Three-dimensional data sets from healthy adult Merino sheep (Ovis orientalis aries, 12 ewes and 26 neutered rams) were acquired on a 1.5 T Philips MRI using a T1w sequence. Data were averaged by linear and non-linear registration algorithms. Moreover, animals were subjected to detailed brain volume analysis including examinations with respect to body weight (BW), age, and sex. The created T1w brain template provides an appropriate population-averaged ovine brain anatomy in a spatial standard coordinate system. Additionally, TPM for gray (GM) and white (WM) matter as well as cerebrospinal fluid (CSF) classification enabled automatic prior-based tissue segmentation using statistical parametric mapping (SPM). Overall, a positive correlation of GM volume and BW explained about 15% of the variance of GM while a positive correlation between WM and age was found. Absolute tissue volume differences were not detected, indeed ewes showed significantly more GM per bodyweight as compared to neutered rams. The created framework including spatial brain template and TPM represent a useful tool for unbiased automatic image preprocessing and morphological characterization in sheep. Therefore, the reported results may serve as a starting point for further experimental and/or translational research aiming at in vivo analysis in this species. PMID:26089780

  14. A stereotaxic, population-averaged T1w ovine brain atlas including cerebral morphology and tissue volumes

    PubMed Central

    Nitzsche, Björn; Frey, Stephen; Collins, Louis D.; Seeger, Johannes; Lobsien, Donald; Dreyer, Antje; Kirsten, Holger; Stoffel, Michael H.; Fonov, Vladimir S.; Boltze, Johannes

    2015-01-01

    Standard stereotaxic reference systems play a key role in human brain studies. Stereotaxic coordinate systems have also been developed for experimental animals including non-human primates, dogs, and rodents. However, they are lacking for other species being relevant in experimental neuroscience including sheep. Here, we present a spatial, unbiased ovine brain template with tissue probability maps (TPM) that offer a detailed stereotaxic reference frame for anatomical features and localization of brain areas, thereby enabling inter-individual and cross-study comparability. Three-dimensional data sets from healthy adult Merino sheep (Ovis orientalis aries, 12 ewes and 26 neutered rams) were acquired on a 1.5 T Philips MRI using a T1w sequence. Data were averaged by linear and non-linear registration algorithms. Moreover, animals were subjected to detailed brain volume analysis including examinations with respect to body weight (BW), age, and sex. The created T1w brain template provides an appropriate population-averaged ovine brain anatomy in a spatial standard coordinate system. Additionally, TPM for gray (GM) and white (WM) matter as well as cerebrospinal fluid (CSF) classification enabled automatic prior-based tissue segmentation using statistical parametric mapping (SPM). Overall, a positive correlation of GM volume and BW explained about 15% of the variance of GM while a positive correlation between WM and age was found. Absolute tissue volume differences were not detected, indeed ewes showed significantly more GM per bodyweight as compared to neutered rams. The created framework including spatial brain template and TPM represent a useful tool for unbiased automatic image preprocessing and morphological characterization in sheep. Therefore, the reported results may serve as a starting point for further experimental and/or translational research aiming at in vivo analysis in this species. PMID:26089780

  15. Research on the human brain in an epilepsy surgery setting.

    PubMed

    Engel, J

    1998-09-01

    Recent advances in our understanding of the fundamental mechanisms of epilepsy have derived, to a large extent, from improvements in designing parallel human and animal studies. This is the result not only of better animal models of human epileptic phenomena, but of an increasing ability to carry out detailed invasive studies on patients in the course of surgical treatment for medically refractory epilepsy. In addition to interictal and ictal video-EEG recordings with chronic depth and subdural electrodes, it is also possible to sample single-unit activity with chronically implanted microelectrodes, and measure constituents of extracellular fluid with chronically implanted microdialysis probes, using protocols that in the past were possible only in the experimental animal laboratory. Subsequent surgical resection provides tissue that can be used for electrophysiological, morphological, biochemical, and molecular biological investigations. Patients in epilepsy surgery facilities represent a precious resource for research that should be utilized to the fullest extent possible by basic scientists interested in mechanisms of epilepsy. It is particularly important that invasive research be pursued now, because improved diagnostic technology is greatly reducing the need for chronic intracranial electrode recordings, and surgical approaches that do not yield tissue could be used more commonly in the future. Therefore, the capacity to carry out invasive research in the context of epilepsy surgery may diminish greatly over time. To take full advantage of these opportunities, carefully designed iterative experimental protocols are necessary to characterize abnormalities in the human epileptic brain, to create appropriate experimental animal models to study these phenomena in greater detail, and to return to the human brain to validate the clinical relevance of observations made on animals. It is also important, however, to recognize certain unavoidable limitations of human

  16. Molecular biology of the human brain

    SciTech Connect

    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.

  17. Unique human orbital morphology compared with that of apes.

    PubMed

    Denion, Eric; Hitier, Martin; Guyader, Vincent; Dugué, Audrey-Emmanuelle; Mouriaux, Frédéric

    2015-01-01

    Humans' and apes' convergent (front-facing) orbits allow a large overlap of monocular visual fields but are considered to limit the lateral visual field extent. However, humans can greatly expand their lateral visual fields using eye motion. This study aimed to assess whether the human orbital morphology was unique compared with that of apes in avoiding lateral visual field obstruction. The orbits of 100 human skulls and 120 ape skulls (30 gibbons; 30 orangutans; 30 gorillas; 30 chimpanzees and bonobos) were analyzed. The orbital width/height ratio was calculated. Two orbital angles representing orbital convergence and rearward position of the orbital margin respectively were recorded using a protractor and laser levels. Humans have the largest orbital width/height ratio (1.19; p < 0.001). Humans and gibbons have orbits which are significantly less convergent than those of chimpanzees/bonobos, gorillas and orangutans (p < 0.001). These elements suggest a morphology favoring lateral vision in humans. More specifically, the human orbit has a uniquely rearward temporal orbital margin (107.1°; p < 0.001), suitable for avoiding visual obstruction and promoting lateral visual field expansion through eye motion. Such an orbital morphology may have evolved mainly as an adaptation to open-country habitat and bipedal locomotion. PMID:26111067

  18. Mouse Genetic Models of Human Brain Disorders.

    PubMed

    Leung, Celeste; Jia, Zhengping

    2016-01-01

    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 behavioral 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. PMID:27047540

  19. Mouse Genetic Models of Human Brain Disorders

    PubMed Central

    Leung, Celeste; Jia, Zhengping

    2016-01-01

    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 behavioral 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. PMID:27047540

  20. New paradigm to assess brain cell morphology by diffusion-weighted MR spectroscopy in vivo

    PubMed Central

    Palombo, Marco; Ligneul, Clémence; Najac, Chloé; Le Douce, Juliette; Flament, Julien; Escartin, Carole; Hantraye, Philippe; Brouillet, Emmanuel; Bonvento, Gilles; Valette, Julien

    2016-01-01

    The brain is one of the most complex organs, and tools are lacking to assess its cellular morphology in vivo. Here we combine original diffusion-weighted magnetic resonance (MR) spectroscopy acquisition and novel modeling strategies to explore the possibility of quantifying brain cell morphology noninvasively. First, the diffusion of cell-specific metabolites is measured at ultra-long diffusion times in the rodent and primate brain in vivo to observe how cell long-range morphology constrains metabolite diffusion. Massive simulations of particles diffusing in synthetic cells parameterized by morphometric statistics are then iterated to fit experimental data. This method yields synthetic cells (tentatively neurons and astrocytes) that exhibit striking qualitative and quantitative similarities with histology (e.g., using Sholl analysis). With our approach, we measure major interspecies difference regarding astrocytes, whereas dendritic organization appears better conserved throughout species. This work suggests that the time dependence of metabolite diffusion coefficient allows distinguishing and quantitatively characterizing brain cell morphologies noninvasively. PMID:27226303

  1. Gross Brain Morphology in Schizophrenia: A Regional Analysis of Traditional Diagnostic Subtypes.

    ERIC Educational Resources Information Center

    Raz, Sarah

    1994-01-01

    Categorized 56 patients with chronic schizophrenia into 2 groups based on traditional diagnostic subtypology. Compared groups on indices of cortical and subcortical cerebrospinal fluid (SCF) volume to explore whether more virulent nonparanoid disorder was linked to cortical/subcortical morphological brain abnormalities. Two groups differed…

  2. New paradigm to assess brain cell morphology by diffusion-weighted MR spectroscopy in vivo.

    PubMed

    Palombo, Marco; Ligneul, Clémence; Najac, Chloé; Le Douce, Juliette; Flament, Julien; Escartin, Carole; Hantraye, Philippe; Brouillet, Emmanuel; Bonvento, Gilles; Valette, Julien

    2016-06-14

    The brain is one of the most complex organs, and tools are lacking to assess its cellular morphology in vivo. Here we combine original diffusion-weighted magnetic resonance (MR) spectroscopy acquisition and novel modeling strategies to explore the possibility of quantifying brain cell morphology noninvasively. First, the diffusion of cell-specific metabolites is measured at ultra-long diffusion times in the rodent and primate brain in vivo to observe how cell long-range morphology constrains metabolite diffusion. Massive simulations of particles diffusing in synthetic cells parameterized by morphometric statistics are then iterated to fit experimental data. This method yields synthetic cells (tentatively neurons and astrocytes) that exhibit striking qualitative and quantitative similarities with histology (e.g., using Sholl analysis). With our approach, we measure major interspecies difference regarding astrocytes, whereas dendritic organization appears better conserved throughout species. This work suggests that the time dependence of metabolite diffusion coefficient allows distinguishing and quantitatively characterizing brain cell morphologies noninvasively. PMID:27226303

  3. Unique human orbital morphology compared with that of apes

    PubMed Central

    Denion, Eric; Hitier, Martin; Guyader, Vincent; Dugué, Audrey-Emmanuelle; Mouriaux, Frédéric

    2015-01-01

    Humans’ and apes’ convergent (front-facing) orbits allow a large overlap of monocular visual fields but are considered to limit the lateral visual field extent. However, humans can greatly expand their lateral visual fields using eye motion. This study aimed to assess whether the human orbital morphology was unique compared with that of apes in avoiding lateral visual field obstruction. The orbits of 100 human skulls and 120 ape skulls (30 gibbons; 30 orangutans; 30 gorillas; 30 chimpanzees and bonobos) were analyzed. The orbital width/height ratio was calculated. Two orbital angles representing orbital convergence and rearward position of the orbital margin respectively were recorded using a protractor and laser levels. Humans have the largest orbital width/height ratio (1.19; p < 0.001). Humans and gibbons have orbits which are significantly less convergent than those of chimpanzees / bonobos, gorillas and orangutans (p < 0.001). These elements suggest a morphology favoring lateral vision in humans. More specifically, the human orbit has a uniquely rearward temporal orbital margin (107.1°; p < 0.001), suitable for avoiding visual obstruction and promoting lateral visual field expansion through eye motion. Such an orbital morphology may have evolved mainly as an adaptation to open-country habitat and bipedal locomotion. PMID:26111067

  4. The shape of the human language-ready brain.

    PubMed

    Boeckx, Cedric; Benítez-Burraco, Antonio

    2014-01-01

    Our core hypothesis is that the emergence of our species-specific language-ready brain ought to be understood in light of the developmental changes expressed at the levels of brain morphology and neural connectivity that occurred in our species after the split from Neanderthals-Denisovans and that gave us a more globular braincase configuration. In addition to changes at the cortical level, we hypothesize that the anatomical shift that led to globularity also entailed significant changes at the subcortical level. We claim that the functional consequences of such changes must also be taken into account to gain a fuller understanding of our linguistic capacity. Here we focus on the thalamus, which we argue is central to language and human cognition, as it modulates fronto-parietal activity. With this new neurobiological perspective in place, we examine its possible molecular basis. We construct a candidate gene set whose members are involved in the development and connectivity of the thalamus, in the evolution of the human head, and are known to give rise to language-associated cognitive disorders. We submit that the new gene candidate set opens up new windows into our understanding of the genetic basis of our linguistic capacity. Thus, our hypothesis aims at generating new testing grounds concerning core aspects of language ontogeny and phylogeny. PMID:24772099

  5. The shape of the human language-ready brain

    PubMed Central

    Boeckx, Cedric; Benítez-Burraco, Antonio

    2014-01-01

    Our core hypothesis is that the emergence of our species-specific language-ready brain ought to be understood in light of the developmental changes expressed at the levels of brain morphology and neural connectivity that occurred in our species after the split from Neanderthals–Denisovans and that gave us a more globular braincase configuration. In addition to changes at the cortical level, we hypothesize that the anatomical shift that led to globularity also entailed significant changes at the subcortical level. We claim that the functional consequences of such changes must also be taken into account to gain a fuller understanding of our linguistic capacity. Here we focus on the thalamus, which we argue is central to language and human cognition, as it modulates fronto-parietal activity. With this new neurobiological perspective in place, we examine its possible molecular basis. We construct a candidate gene set whose members are involved in the development and connectivity of the thalamus, in the evolution of the human head, and are known to give rise to language-associated cognitive disorders. We submit that the new gene candidate set opens up new windows into our understanding of the genetic basis of our linguistic capacity. Thus, our hypothesis aims at generating new testing grounds concerning core aspects of language ontogeny and phylogeny. PMID:24772099

  6. Evolution, development, and plasticity of the human brain: from molecules to bones.

    PubMed

    Hrvoj-Mihic, Branka; Bienvenu, Thibault; Stefanacci, Lisa; Muotri, Alysson R; Semendeferi, Katerina

    2013-01-01

    Neuroanatomical, molecular, and paleontological evidence is examined in light of human brain evolution. The brain of extant humans differs from the brains of other primates in its overall size and organization, and differences in size and organization of specific cortical areas and subcortical structures implicated into complex cognition and social and emotional processing. The human brain is also characterized by functional lateralizations, reflecting specializations of the cerebral hemispheres in humans for different types of processing, facilitating fast and reliable communication between neural cells in an enlarged brain. The features observed in the adult brain reflect human-specific patterns of brain development. Compared to the brains of other primates, the human brain takes longer to mature, promoting an extended period for establishing cortical microcircuitry and its modifications. Together, these features may underlie the prolonged period of learning and acquisition of technical and social skills necessary for survival, creating a unique cognitive and behavioral niche typical of our species. The neuroanatomical findings are in concordance with molecular analyses, which suggest a trend toward heterochrony in the expression of genes implicated in different functions. These include synaptogenesis, neuronal maturation, and plasticity in humans, mutations in genes implicated in neurite outgrowth and plasticity, and an increased role of regulatory mechanisms, potentially promoting fast modification of neuronal morphologies in response to new computational demands. At the same time, endocranial casts of fossil hominins provide an insight into the timing of the emergence of uniquely human features in the course of evolution. We conclude by proposing several ways of combining comparative neuroanatomy, molecular biology and insights gained from fossil endocasts in future research. PMID:24194709

  7. Evolution, development, and plasticity of the human brain: from molecules to bones

    PubMed Central

    Hrvoj-Mihic, Branka; Bienvenu, Thibault; Stefanacci, Lisa; Muotri, Alysson R.; Semendeferi, Katerina

    2013-01-01

    Neuroanatomical, molecular, and paleontological evidence is examined in light of human brain evolution. The brain of extant humans differs from the brains of other primates in its overall size and organization, and differences in size and organization of specific cortical areas and subcortical structures implicated into complex cognition and social and emotional processing. The human brain is also characterized by functional lateralizations, reflecting specializations of the cerebral hemispheres in humans for different types of processing, facilitating fast and reliable communication between neural cells in an enlarged brain. The features observed in the adult brain reflect human-specific patterns of brain development. Compared to the brains of other primates, the human brain takes longer to mature, promoting an extended period for establishing cortical microcircuitry and its modifications. Together, these features may underlie the prolonged period of learning and acquisition of technical and social skills necessary for survival, creating a unique cognitive and behavioral niche typical of our species. The neuroanatomical findings are in concordance with molecular analyses, which suggest a trend toward heterochrony in the expression of genes implicated in different functions. These include synaptogenesis, neuronal maturation, and plasticity in humans, mutations in genes implicated in neurite outgrowth and plasticity, and an increased role of regulatory mechanisms, potentially promoting fast modification of neuronal morphologies in response to new computational demands. At the same time, endocranial casts of fossil hominins provide an insight into the timing of the emergence of uniquely human features in the course of evolution. We conclude by proposing several ways of combining comparative neuroanatomy, molecular biology and insights gained from fossil endocasts in future research. PMID:24194709

  8. What happens in the leucotomised brain? A postmortem morphological study of brains from schizophrenic patients.

    PubMed Central

    Pakkenberg, B

    1989-01-01

    Volume measurements were carried out on 19 brains from leucotomised schizophrenic patients and 20 age- and sex-matched controls using a stereological method. The volume of the total fixed brain, hemispheres, cortex, white matter, and central grey matter were all significantly reduced compared with controls. White matter and central grey structures were significantly reduced compared with a group of non-leucotomised schizophrenic brains. No difference was found in the size of the lesions in patients who improved compared with the patients who remained unchanged and the outcome was unrelated to lesional asymmetry. Morphometric measurements were correlated to a number of clinical parameters. PMID:2703834

  9. Exercises in Anatomy, Connectivity, and Morphology using Neuromorpho.org and the Allen Brain Atlas

    PubMed Central

    Chu, Philip; Peck, Joshua; Brumberg, Joshua C.

    2015-01-01

    Laboratory instruction of neuroscience is often limited by the lack of physical resources and supplies (e.g., brains specimens, dissection kits, physiological equipment). Online databases can serve as supplements to material labs by providing professionally collected images of brain specimens and their underlying cellular populations with resolution and quality that is extremely difficult to access for strictly pedagogical purposes. We describe a method using two online databases, the Neuromorpho.org and the Allen Brain Atlas (ABA), that freely provide access to data from working brain scientists that can be modified for laboratory instruction/exercises. Neuromorpho.org is the first neuronal morphology database that provides qualitative and quantitative data from reconstructed cells analyzed in published scientific reports. The Neuromorpho.org database contains cross species and multiple neuronal phenotype datasets which allows for comparative examinations. The ABA provides modules that allow students to study the anatomy of the rodent brain, as well as observe the different cellular phenotypes that exist using histochemical labeling. Using these tools in conjunction, advanced students can ask questions about qualitative and quantitative neuronal morphology, then examine the distribution of the same cell types across the entire brain to gain a full appreciation of the magnitude of the brain’s complexity. PMID:25838808

  10. RECONSTRUCTION OF HUMAN LUNG MORPHOLOGY MODELS FROM MAGNETIC RESONANCE IMAGES

    EPA Science Inventory


    Reconstruction of Human Lung Morphology Models from Magnetic Resonance Images
    T. B. Martonen (Experimental Toxicology Division, U.S. EPA, Research Triangle Park, NC 27709) and K. K. Isaacs (School of Public Health, University of North Carolina, Chapel Hill, NC 27514)

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

    PubMed Central

    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

  12. [Neuroethics: Ethical Endowments of Human Brain].

    PubMed

    López Moratalla, Natalia

    2015-01-01

    The neurobiological processes underlying moral judgement have been the focus of Neuroethics. Neurosciences demonstrate which cerebral areas are active and inactive whilst people decide how to act when facing a moral dilemma; in this way we know the correlation between determined cerebral areas and our human acts. We can explain how the ″ethical endowments″ of each person, common to all human beings, is ″embedded″ in the dynamic of cerebral flows. Of central interest is whether emotions play a causal role in moral judgement, and, in parallel, how emotion related areas of the brain contribute to moral judgement. The outcome of man's natural inclinations is on one hand linked to instinctive systems of animal survival and to basic emotions, and on the other, to the life of each individual human uninhibited by automatism of the biological laws, because he is governed by the laws of freedom. The capacity to formulate an ethical judgement is an innate asset of the human mind. PMID:26546796

  13. Unraveling the fundamental molecular mechanisms of morphological and cognitive defects in the irradiated brain.

    PubMed

    Verheyde, Joris; Benotmane, Mohammed Abderrafi

    2007-02-01

    Prenatal radiation exposure may have serious consequences for normal brain development. Results of epidemiological studies clearly pointed towards an increased risk of mental retardation in children of the surviving women of the Hiroshima/Nagasaki atomic bombing when in utero exposure had occurred between weeks 8 and 15 of pregnancy or, at a lower extend between weeks 15 and 25. The high sensitivity of the developing brain, in comparison to the adult brain is related to its higher number of non-differentiated, dividing neural precursor cells. Exposure of the developing brain to ionizing radiation can lead to three main outcomes in the developing brain, depending on the radiation dose and the elapsed period after irradiation. A first event occurs early after irradiation and triggers disturbances in cell proliferation, migration, differentiation, and cell death. A second event involves the generation of morphological abnormalities in the developing brain, if the radiation dose is sufficient. A third event involves cognitive dysfunctions that are a direct consequence from a disturbance in regional brain formation. The latter results from exposure to low doses and is usually only observed in the later period of development. In order to understand the mechanisms of radiation-induced cognitive dysfunctions, it is important to track back the underlying changes in specific molecular pathways. In this review, we present the possible relationships within and between molecular pathways potentially involved in cognitive dysfunctions induced by ionizing radiation in the developing brain. PMID:17188364

  14. Predicting human age using regional morphometry and inter-regional morphological similarity

    NASA Astrophysics Data System (ADS)

    Wang, Xun-Heng; Li, Lihua

    2016-03-01

    The goal of this study is predicting human age using neuro-metrics derived from structural MRI, as well as investigating the relationships between age and predictive neuro-metrics. To this end, a cohort of healthy subjects were recruited from 1000 Functional Connectomes Project. The ages of the participations were ranging from 7 to 83 (36.17+/-20.46). The structural MRI for each subject was preprocessed using FreeSurfer, resulting in regional cortical thickness, mean curvature, regional volume and regional surface area for 148 anatomical parcellations. The individual age was predicted from the combination of regional and inter-regional neuro-metrics. The prediction accuracy is r = 0.835, p < 0.00001, evaluated by Pearson correlation coefficient between predicted ages and actual ages. Moreover, the LASSO linear regression also found certain predictive features, most of which were inter-regional features. The turning-point of the developmental trajectories in human brain was around 40 years old based on regional cortical thickness. In conclusion, structural MRI could be potential biomarkers for the aging in human brain. The human age could be successfully predicted from the combination of regional morphometry and inter-regional morphological similarity. The inter-regional measures could be beneficial to investigating human brain connectome.

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

    ERIC Educational Resources Information Center

    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)

  16. Listeriolysin O mediates cytotoxicity against human brain microvascular

    Technology Transfer Automated Retrieval System (TEKTRAN)

    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...

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

    PubMed

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

    2016-07-01

    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. PMID:27459595

  18. Spread of epileptic activity in human brain

    NASA Astrophysics Data System (ADS)

    Milton, John

    1997-03-01

    For many patients with medically refractory epilepsy surgical resection of the site of seizure onset (epileptic focus) offers the best hope for cure. Determination of the nature of seizure propagation should lead to improved methods for locating the epileptic focus (and hence reduce patient morbidity) and possibly to new treatment modalities directed at blocking seizure spread. Theoretical studies of neural networks emphasize the role of traveling waves for the propagation of activity. However, the nature of seizure propagation in human brain remains poorly characterized. The spread of epileptic activity in patients undergoing presurgical evaluation for epilepsy surgery was measured by placing subdural grids of electrodes (interelectrode spacings of 3-10 mm) over the frontal and temporal lobes. The exact location of each electrode relative to the surface of the brain was determined using 3--D MRI imaging techniques. Thus it is possible to monitor the spread of epileptic activity in both space and time. The observations are discussed in light of models for seizure propagation.

  19. Proton spectroscopic imaging of human brain

    NASA Astrophysics Data System (ADS)

    Moonen, Chrit T. W.; Sobering, Geoffrey; Van Zijl, Peter C. M.; Gillen, Joe; Von Kienlin, Markus; Bizzi, Alberto

    Signals from water and fat can cause artifacts in proton spectroscopic imaging in the human brain. The major problem is variation of the B0 field over a range of several ppm within the sensitive volume of the standard whole-head coil. Here, the coherence-pathway formalism is used to describe and evaluate the origin of artifacts in a double spin-echo (PRESS) sequence. The attenuation of unwanted coherences using pulsed field gradients is described for homogeneous and inhomogeneous B0 fields. The effect of the following parameters on the quality of the spectroscopic images is analyzed: (a) directional order of plane selection, (b) positioning of phase-encode gradients in the sequence, (c) postprocessing spatial windowing, and (d) motion. It is shown that, for a typical echo time of 272 ms, it is not necessary to first select a region of interest within the brain borders when sufficient phase-encode steps are used. Examples of 2D proton spectroscopic images with a nominal voxel volume of 0.85 ml are given for a healthy volunteer and a patient with a low-grade glioma.

  20. Influence of curvature on the morphology of brain microvascular endothelial cells

    NASA Astrophysics Data System (ADS)

    Ye, Mao; Yang, Zhen; Wong, Andrew; Searson, Peter; Searson Group Team

    2013-03-01

    There are hundreds or thousands of endothelial cells around the perimeter of a single artery or vein, and hence an individual cell experiences little curvature. In contrast, a single endothelial cell may wrap around itself to form the lumen of a brain capillary. Curvature plays a key role in many biological, chemical and physical processes, however, its role in dictating the morphology and polarization of brain capillary endothelial cells has not been investigated. We hypothesize that curvature and shear flow play a key role in determining the structure and function of the blood-brain barrier (BBB). We have developed the ``rod'' assay to study the influence of curvature on the morphology of confluent monolayers of endothelial cells. In this assay cells are plated onto glass rods pulled down to the desired diameter in the range from 5 - 500 μm and coated with collagen. We show that curvature has a significant influence on the morphology of endothelial cells and may have an important role in blood-brain barrier function.

  1. Evaluating the microstructure of human brain tissues using synchrotron radiation-based micro-computed tomography

    NASA Astrophysics Data System (ADS)

    Schulz, Georg; Morel, Anne; Imholz, Martha S.; Deyhle, Hans; Weitkamp, Timm; Zanette, Irene; Pfeiffer, Franz; David, Christian; Müller-Gerbl, Magdalena; Müller, Bert

    2010-09-01

    Minimally invasive deep brain neurosurgical interventions require a profound knowledge of the morphology of the human brain. Generic brain atlases are based on histology including multiple preparation steps during the sectioning and staining. In order to correct the distortions induced in the anisotropic, inhomogeneous soft matter and therefore improve the accuracy of brain atlases, a non-destructive 3D imaging technique with the required spatial and density resolution is of great significance. Micro computed tomography provides true micrometer resolution. The application to post mortem human brain, however, is questionable because the differences of the components concerning X-ray absorption are weak. Therefore, magnetic resonance tomography has become the method of choice for three-dimensional imaging of human brain. Because the spatial resolution of this method is limited, an alternative has to be found for the three-dimensional imaging of cellular microstructures within the brain. Therefore, the present study relies on the synchrotron radiationbased micro computed tomography in the recently developed grating-based phase contrast mode. Using data acquired at the beamline ID 19 (ESRF, Grenoble, France) we demonstrate that grating-based tomography yields premium images of human thalamus, which can be used for the correction of histological distortions by 3D non-rigid registration.

  2. Moment-to-moment brain signal variability: A next frontier in human brain mapping?

    PubMed Central

    Garrett, Douglas D.; Samanez-Larkin, Gregory R.; MacDonald, Stuart W.S.; Lindenberger, Ulman; McIntosh, Anthony R.; Grady, Cheryl L.

    2013-01-01

    Neuroscientists have long observed that brain activity is naturally variable from moment-to-moment, but neuroimaging research has largely ignored the potential importance of this phenomenon. An emerging research focus on within-person brain signal variability is providing novel insights, and offering highly predictive, complementary, and even orthogonal views of brain function in relation to human life-span development, cognitive performance, and various clinical conditions. As a result, brain signal variability is evolving as a bona fide signal of interest, and should no longer be dismissed as meaningless noise when mapping the human brain. PMID:23458776

  3. Prenatal Tobacco Exposure and Brain Morphology: A Prospective Study in Young Children

    PubMed Central

    El Marroun, Hanan; Schmidt, Marcus N; Franken, Ingmar H A; Jaddoe, Vincent W V; Hofman, Albert; van der Lugt, Aad; Verhulst, Frank C; Tiemeier, Henning; White, Tonya

    2014-01-01

    It is well known that smoking during pregnancy can affect offspring health. Prenatal tobacco exposure has been associated with negative behavioral and cognitive outcomes in childhood, adolescence, and young adulthood. These associations between prenatal tobacco exposure and psychopathology in offspring could possibly be explained by the influence of prenatal tobacco exposure on brain development. In this prospective study, we investigated the association between prenatal tobacco exposure, behavioral and emotional functioning and brain morphology in young children. On the basis of age and gender, we matched 113 children prenatally exposed to tobacco with 113 unexposed controls. These children were part of a population-based study in the Netherlands, the Generation R Study, and were followed from pregnancy onward. Behavioral and emotional functioning was assessed at age 6 with the Child Behavior Checklist. We assessed brain morphology using magnetic resonance imaging techniques in children aged 6–8 years. Children exposed to tobacco throughout pregnancy have smaller total brain volumes and smaller cortical gray matter volumes. Continued prenatal tobacco exposure was associated with cortical thinning, primarily in the superior frontal, superior parietal, and precentral cortices. These children also demonstrated increased scores of affective problems. In addition, thickness of the precentral and superior frontal cortices was associated with affective problems. Importantly, brain development in offspring of mothers who quit smoking during pregnancy resembled that of nonexposed controls (no smaller brain volumes and no thinning of the cortex). Our findings suggest an association between continued prenatal tobacco exposure and brain structure and function in school-aged children. PMID:24096296

  4. Classification of normal and pathological aging processes based on brain MRI morphology measures

    NASA Astrophysics Data System (ADS)

    Perez-Gonzalez, J. L.; Yanez-Suarez, O.; Medina-Bañuelos, V.

    2014-03-01

    Reported studies describing normal and abnormal aging based on anatomical MRI analysis do not consider morphological brain changes, but only volumetric measures to distinguish among these processes. This work presents a classification scheme, based both on size and shape features extracted from brain volumes, to determine different aging stages: healthy control (HC) adults, mild cognitive impairment (MCI), and Alzheimer's disease (AD). Three support vector machines were optimized and validated for the pair-wise separation of these three classes, using selected features from a set of 3D discrete compactness measures and normalized volumes of several global and local anatomical structures. Our analysis show classification rates of up to 98.3% between HC and AD; of 85% between HC and MCI and of 93.3% for MCI and AD separation. These results outperform those reported in the literature and demonstrate the viability of the proposed morphological indexes to classify different aging stages.

  5. Neuroanatomical and morphological trait clusters in the ant genus Pheidole: evidence for modularity and integration in brain structure.

    PubMed

    Ilieş, Iulian; Muscedere, Mario L; Traniello, James F A

    2015-01-01

    A central question in brain evolution concerns how selection has structured neuromorphological variation to generate adaptive behavior. In social insects, brain structures differ between reproductive and sterile castes, and worker behavioral specializations related to morphology, age, and ecology are associated with intra- and interspecific variation in investment in functionally different brain compartments. Workers in the hyperdiverse ant genus Pheidole are morphologically and behaviorally differentiated into minor and major subcastes that exhibit distinct species-typical patterns of brain compartment size variation. We examined integration and modularity in brain organization and its developmental patterning in three ecotypical Pheidole species by analyzing intra- and interspecific morphological and neuroanatomical covariation. Our results identified two trait clusters, the first involving olfaction and social information processing and the second composed of brain regions regulating nonolfactory sensorimotor functions. Patterns of size covariation between brain compartments within subcastes were consistent with levels of behavioral differentiation between minor and major workers. Globally, brains of mature workers were more heterogeneous than brains of newly eclosed workers, suggesting diversified developmental trajectories underscore species- and subcaste-typical brain organization. Variation in brain structure associated with the striking worker polyphenism in our sample of Pheidole appears to originate from initially differentiated brain templates that further diverge through species- and subcaste-specific processes of maturation and behavioral development. PMID:25766867

  6. Sports and brain morphology - a voxel-based morphometry study with endurance athletes and martial artists.

    PubMed

    Schlaffke, L; Lissek, S; Lenz, M; Brüne, M; Juckel, G; Hinrichs, T; Platen, P; Tegenthoff, M; Schmidt-Wilcke, T

    2014-02-14

    Physical exercises and motor skill learning have been shown to induce changes in regional brain morphology, this has been demonstrated for various activities and tasks. Also individuals with special skills show differences in regional brain morphology. This has been indicated for professional musicians, London taxi drivers, as well as for athletes like dancers, golfers and judokas. However little is known about whether sports with different metabolic profiles (aerobic vs. anaerobic) are associated with different patterns of altered brain morphology. In this cross-sectional study we investigated two groups of high-performance athletes, one group performing sports that are thought to be mainly aerobic, and one group performing sports known to have intermittent phases of anaerobic metabolism. Using high-resolution structural imaging and voxel-based morphometry (VBM), we investigated a group of 26 male athletes consisting of 13 martial artists and 13 endurance athletes as well as a group of non-exercising men (n=13). VBM analyses revealed higher gray matter (GM) volumes in the supplementary motor area/dorsal premotor cortex (BA 6) in both athlete groups as compared to the control group. In addition, endurance athletes showed significantly higher GM volume in the medial temporal lobe (MTL), specifically in the hippocampus and parahippocampal gyrus, which was not seen in the martial arts group. Our data suggest that high-performance sports are associated with changes in regional brain morphology in areas implicated in motor planning and motor learning. In addition high-level endurance sports seem to affect MTL structures, areas that have previously been shown to be modulated by aerobic exercise. PMID:24291669

  7. The disturbed blood-brain barrier in human glioblastoma.

    PubMed

    Wolburg, Hartwig; Noell, Susan; Fallier-Becker, Petra; Mack, Andreas F; Wolburg-Buchholz, Karen

    2012-01-01

    The aim of this article is to describe alterations of the blood-brain barrier (BBB) in gliomas. The main clinical problem of human gliomas is the edematous swelling and the dramatic increase of intracerebral pressure, also compromising healthy areas of the brain. According to our concept, one of the main reasons on the cellular level for these clinical problems is the loss or reduction of astroglial polarity. Astroglial polarity means the specific accumulation of potassium and water channels in the superficial and perivascular astroglial endfeet membranes. The most important water channel in the CNS is the astroglial water channel protein aquaporin-4 (AQP4) which is arranged in a morphologically spectacular way, the so-called orthogonal arrays of particles (OAPs) to be observed in freeze-fracture replicas. In brain tumors, but also under conditions of trauma or inflammation, these OAPs are redistributed to membrane domains apart from endfeet areas. Probably, this dislocation might be due to the degradation of the proteoglycan agrin by the matrix metalloproteinase 3 (MMP3). Agrin binds to the dystrophin-dystroglycan-complex (DDC), which in turn is connected to AQP4. As a consequence, agrin loss may lead to a redistribution of AQP4 and a compromised directionality of water transport out of the cell, finally to cytotoxic edema. This in turn is hypothesized to lead to a breakdown of the BBB characterized by disturbed tight junctions, and thus to the development of vasogenic edema. However, the mechanism how the loss of polarity is related to the disturbance of microvascular tight junctions is completely unknown so far. PMID:22387049

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

    PubMed

    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

    2014-09-01

    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

  9. Flunarizine limits hypoxia-ischemia induced morphologic injury in immature rat brain.

    PubMed

    Silverstein, F S; Buchanan, K; Hudson, C; Johnston, M V

    1986-01-01

    We examined the impact of pre-treatment with the calcium antagonist flunarizine on the development of hypoxic-ischemic brain injury in the immature rat. Unilateral carotid artery ligation and subsequent exposure to 2 hours of 8% oxygen in 7-day-old rats was used as a model for perinatal hypoxic-ischemic encephalopathy. This procedure leads to atrophy in the cerebral hemisphere ipsilateral to carotid occlusion, with prominent foci of neuronal infarction in the caudate-putamen (striatum). The morphologic injury develops after 1 1/2 hours of hypoxia; and there is an equivalent time threshold for duration of hypoxic exposure needed to acutely stimulate dopamine release in the ipsilateral striatum. Parenteral administration of 30 mg/kg of flunarizine before hypoxic exposure limited both the release of dopamine acutely and the extent of morphologic damage observed two weeks after the insult. Oral administration of 30 mg/kg of flunarizine in a different vehicle prevented morphologic damage but had no effect on stimulated dopamine release. The drug vehicle for the parenteral preparation also prevented tissue injury, but to a lesser degree than flunarizine. However the parenteral vehicle was equipotent with parenteral flunarizine in limiting acute stimulation of dopamine release. The results demonstrate that flunarizine has potent neuroprotective properties against morphologic brain injury from hypoxia-ischemia, acting by a mechanism which is independent of effects on dopamine release. PMID:3715946

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

    PubMed Central

    Atasoy, Selen; Donnelly, Isaac; Pearson, Joel

    2016-01-01

    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. PMID:26792267

  11. Aneuploidy and Confined Chromosomal Mosaicism in the Developing Human Brain

    PubMed Central

    Liehr, Thomas; Kolotii, Alexei D.; Kutsev, Sergei I.; Pellestor, Franck; Beresheva, Alfia K.; Demidova, Irina A.; Kravets, Viktor S.; Monakhov, Viktor V.; Soloviev, Ilia V.

    2007-01-01

    Background Understanding the mechanisms underlying generation of neuronal variability and complexity remains the central challenge for neuroscience. Structural variation in the neuronal genome is likely to be one important mechanism for neuronal diversity and brain diseases. Large-scale genomic variations due to loss or gain of whole chromosomes (aneuploidy) have been described in cells of the normal and diseased human brain, which are generated from neural stem cells during intrauterine period of life. However, the incidence of aneuploidy in the developing human brain and its impact on the brain development and function are obscure. Methodology/Principal Findings To address genomic variation during development we surveyed aneuploidy/polyploidy in the human fetal tissues by advanced molecular-cytogenetic techniques at the single-cell level. Here we show that the human developing brain has mosaic nature, being composed of euploid and aneuploid neural cells. Studying over 600,000 neural cells, we have determined the average aneuploidy frequency as 1.25–1.45% per chromosome, with the overall percentage of aneuploidy tending to approach 30–35%. Furthermore, we found that mosaic aneuploidy can be exclusively confined to the brain. Conclusions/Significance Our data indicates aneuploidization to be an additional pathological mechanism for neuronal genome diversification. These findings highlight the involvement of aneuploidy in the human brain development and suggest an unexpected link between developmental chromosomal instability, intercellural/intertissular genome diversity and human brain diseases. PMID:17593959

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

    PubMed

    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. PMID:26982717

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

    PubMed Central

    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. PMID:26982717

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

    PubMed

    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. PMID:26621705

  15. Genomic connectivity networks based on the BrainSpan atlas of the developing human brain

    NASA Astrophysics Data System (ADS)

    Mahfouz, Ahmed; Ziats, Mark N.; Rennert, Owen M.; Lelieveldt, Boudewijn P. F.; Reinders, Marcel J. T.

    2014-03-01

    The human brain comprises systems of networks that span the molecular, cellular, anatomic and functional levels. Molecular studies of the developing brain have focused on elucidating networks among gene products that may drive cellular brain development by functioning together in biological pathways. On the other hand, studies of the brain connectome attempt to determine how anatomically distinct brain regions are connected to each other, either anatomically (diffusion tensor imaging) or functionally (functional MRI and EEG), and how they change over development. A global examination of the relationship between gene expression and connectivity in the developing human brain is necessary to understand how the genetic signature of different brain regions instructs connections to other regions. Furthermore, analyzing the development of connectivity networks based on the spatio-temporal dynamics of gene expression provides a new insight into the effect of neurodevelopmental disease genes on brain networks. In this work, we construct connectivity networks between brain regions based on the similarity of their gene expression signature, termed "Genomic Connectivity Networks" (GCNs). Genomic connectivity networks were constructed using data from the BrainSpan Transcriptional Atlas of the Developing Human Brain. Our goal was to understand how the genetic signatures of anatomically distinct brain regions relate to each other across development. We assessed the neurodevelopmental changes in connectivity patterns of brain regions when networks were constructed with genes implicated in the neurodevelopmental disorder autism (autism spectrum disorder; ASD). Using graph theory metrics to characterize the GCNs, we show that ASD-GCNs are relatively less connected later in development with the cerebellum showing a very distinct expression of ASD-associated genes compared to other brain regions.

  16. Magnetic Resonance Microscopy at 14 Tesla and Correlative Histopathology of Human Brain Tumor Tissue

    PubMed Central

    Gonzalez-Segura, Ana; Morales, Jose Manuel; Gonzalez-Darder, Jose Manuel; Cardona-Marsal, Ramon; Lopez-Gines, Concepcion; Cerda-Nicolas, Miguel; Monleon, Daniel

    2011-01-01

    Magnetic Resonance Microscopy (MRM) can provide high microstructural detail in excised human lesions. Previous MRM images on some experimental models and a few human samples suggest the large potential of the technique. The aim of this study was the characterization of specific morphological features of human brain tumor samples by MRM and correlative histopathology. We performed MRM imaging and correlative histopathology in 19 meningioma and 11 glioma human brain tumor samples obtained at surgery. To our knowledge, this is the first MRM direct structural characterization of human brain tumor samples. MRM of brain tumor tissue provided images with 35 to 40 µm spatial resolution. The use of MRM to study human brain tumor samples provides new microstructural information on brain tumors for better classification and characterization. The correlation between MRM and histopathology images allowed the determination of image parameters for critical microstructures of the tumor, like collagen patterns, necrotic foci, calcifications and/or psammoma bodies, vascular distribution and hemorrhage among others. Therefore, MRM may help in interpreting the Clinical Magnetic Resonance images in terms of cell biology processes and tissue patterns. Finally, and most importantly for clinical diagnosis purposes, it provides three-dimensional information in intact samples which may help in selecting a preferential orientation for the histopathology slicing which contains most of the informative elements of the biopsy. Overall, the findings reported here provide a new and unique microstructural view of intact human brain tumor tissue. At this point, our approach and results allow the identification of specific tissue types and pathological features in unprocessed tumor samples. PMID:22110653

  17. Modifications in astrocyte morphology and calcium signaling induced by a brain capillary endothelial cell line.

    PubMed

    Yoder, Elizabeth J

    2002-04-15

    Astrocytes extend specialized endfoot processes to perisynaptic and perivascular regions, and thus are positioned to mediate the bidirectional flow of metabolic, ionic, and other transmissive substances between neurons and the blood stream. While mutual structural and functional interactions between neurons and astrocytes have been documented, less is known about the interactions between astrocytes and cerebrovascular cells. For example, although the ability of astrocytes to induce structural and functional changes in endothelial cells is established, the reciprocity of brain endothelial cells to induce changes in astrocytes is undetermined. This issue is addressed in the present study. Changes in primary cultures of neonatal mouse cortical astrocytes were investigated following their coculture with mouse brain capillary endothelial (bEnd3) cells. The presence of bEnd3 cells altered the morphology of astrocytes by transforming them from confluent monolayers into networks of elongated multicellular columns. These columns did not occur when either bEnd3 cells or astrocytes were cocultured with other cell types, suggesting that astrocytes undergo specific morphological consequences when placed in close proximity to brain endothelial cells. In addition to these structural changes, the pharmacological profile of astrocytes was modified by coculture with bEnd3 cells. Astrocytes in the cocultures showed an increased Ca2+ responsiveness to bradykinin and glutamate, but no change in responsiveness to ATP, as compared to controls. Coculturing the astrocytes with a neuronal cell line resulted in increased responsiveness of the glial responses to glutamate but not to bradykinin. These studies indicate that brain endothelial cells induce changes in astrocyte morphology and pharmacology. PMID:11948807

  18. Hemodynamic and morphologic responses in mouse brain during acute head injury imaged by multispectral structured illumination

    NASA Astrophysics Data System (ADS)

    Volkov, Boris; Mathews, Marlon S.; Abookasis, David

    2015-03-01

    Multispectral imaging has received significant attention over the last decade as it integrates spectroscopy, imaging, tomography analysis concurrently to acquire both spatial and spectral information from biological tissue. In the present study, a multispectral setup based on projection of structured illumination at several near-infrared wavelengths and at different spatial frequencies is applied to quantitatively assess brain function before, during, and after the onset of traumatic brain injury in an intact mouse brain (n=5). For the production of head injury, we used the weight drop method where weight of a cylindrical metallic rod falling along a metal tube strikes the mouse's head. Structured light was projected onto the scalp surface and diffuse reflected light was recorded by a CCD camera positioned perpendicular to the mouse head. Following data analysis, we were able to concurrently show a series of hemodynamic and morphologic changes over time including higher deoxyhemoglobin, reduction in oxygen saturation, cell swelling, etc., in comparison with baseline measurements. Overall, results demonstrates the capability of multispectral imaging based structured illumination to detect and map of brain tissue optical and physiological properties following brain injury in a simple noninvasive and noncontact manner.

  19. Morphologic Indication for Proprioception in the Human Ciliary Muscle

    PubMed Central

    Flügel-Koch, Cassandra; Neuhuber, Winfried L.; Kaufman, Paul L.; Lütjen-Drecoll, Elke

    2009-01-01

    Purpose To search for proprioceptive nerve terminals in human ciliary muscle. Methods In 48 human donor eyes, histologic and ultrathin sections cut in different planes and wholemounts of the ciliary muscle were studied. Immunohistochemical staining with antibodies against pan-neuronal antigens and antigens reported as markers for sensory terminals in other organs was performed. Results Among the markers for proprioceptive terminals, only calretinin was present in the ciliary body. Calretinin-immunoreactive (IR) nerve terminals surrounded the posterior and reticular ciliary muscle tips and their elastic tendons. Terminals in that region contained mitochondria and neurofilaments. At the anterior tips larger terminals with numerous membrane-filled vesicles were located between the muscle fibers. The most elaborate network of calretinin-IR nerve fibers was present in the ground plate covering the circular muscle portion. Here calretinin-IR neurons with morphologic features of mechanoreception were present. Within the circular muscle portion numerous calretinin-IR ganglion cells were found. Their processes were connected to the calretinin-IR network but also surrounded ciliary muscle cells and NADPH-diaphorase-positive ganglion cells. Conclusions These morphologic findings indicate that there are proprioreceptors in the ciliary muscle that morphologically and presumably functionally differ at different locations. At the posterior muscle tips, the receptors could measure stretch of the tendons, whereas the large receptor organs located at the anterior muscle tips morphologically resemble mechanoreceptors measuring shear stress. The presence of the numerous intrinsic nerve cells indicates that contraction of the circular muscle portion can be modulated locally via a self-contained reflex arc. PMID:19578020

  20. Parental brain and socioeconomic epigenetic effects in human development

    PubMed Central

    Swain, James E.; Perkins, Suzanne C.; Dayton, Carolyn J.; Finegood, Eric D.; Ho, S. Shaun

    2015-01-01

    Critically significant parental effects in behavioral genetics may be partly understood as a consequence of maternal brain structure and function of caregiving systems recently studied in humans as well as rodents. Key parental brain areas regulate emotions, motivation/reward, and decision making, as well as more complex social-cognitive circuits. Additional key environmental factors must include socioeconomic status and paternal brain physiology. These have implications for developmental and evolutionary biology as well as public policy. PMID:23095400

  1. Morphological brain network assessed using graph theory and network filtration in deaf adults.

    PubMed

    Kim, Eunkyung; Kang, Hyejin; Lee, Hyekyoung; Lee, Hyo-Jeong; Suh, Myung-Whan; Song, Jae-Jin; Oh, Seung-Ha; Lee, Dong Soo

    2014-09-01

    Prolonged deprivation of auditory input can change brain networks in pre- and postlingual deaf adults by brain-wide reorganization. To investigate morphological changes in these brains voxel-based morphometry, voxel-wise correlation with the primary auditory cortex, and whole brain network analyses using morphological covariance were performed in eight prelingual deaf, eleven postlingual deaf, and eleven hearing adults. Network characteristics based on graph theory and network filtration based on persistent homology were examined. Gray matter density in the primary auditor cortex was preserved in prelingual deafness, while it tended to decrease in postlingual deafness. Unlike postlingual, prelingual deafness showed increased bilateral temporal connectivity of the primary auditory cortex compared to the hearing adults. Of the graph theory-based characteristics, clustering coefficient, betweenness centrality, and nodal efficiency all increased in prelingual deafness, while all the parameters of postlingual deafness were similar to the hearing adults. Patterns of connected components changing during network filtration were different between prelingual deafness and hearing adults according to the barcode, dendrogram, and single linkage matrix representations, while these were the same in postlingual deafness. Nodes in fronto-limbic and left temporal components were closely coupled, and nodes in the temporo-parietal component were loosely coupled, in prelingual deafness. Patterns of connected components changing in postlingual deafness were the same as hearing adults. We propose that the preserved density of auditory cortex associated with increased connectivity in prelingual deafness, and closer coupling between certain brain areas, represent distinctive reorganization of auditory and related cortices compared with hearing or postlingual deaf adults. The differential network reorganization in the prelingual deaf adults could be related to the absence of auditory speech

  2. Resonance of human brain under head acceleration.

    PubMed

    Laksari, Kaveh; Wu, Lyndia C; Kurt, Mehmet; Kuo, Calvin; Camarillo, David C

    2015-07-01

    Although safety standards have reduced fatal head trauma due to single severe head impacts, mild trauma from repeated head exposures may carry risks of long-term chronic changes in the brain's function and structure. To study the physical sensitivities of the brain to mild head impacts, we developed the first dynamic model of the skull-brain based on in vivo MRI data. We showed that the motion of the brain can be described by a rigid-body with constrained kinematics. We further demonstrated that skull-brain dynamics can be approximated by an under-damped system with a low-frequency resonance at around 15 Hz. Furthermore, from our previous field measurements, we found that head motions in a variety of activities, including contact sports, show a primary frequency of less than 20 Hz. This implies that typical head exposures may drive the brain dangerously close to its mechanical resonance and lead to amplified brain-skull relative motions. Our results suggest a possible cause for mild brain trauma, which could occur due to repetitive low-acceleration head oscillations in a variety of recreational and occupational activities. PMID:26063824

  3. Sexual selection and the evolution of behavior, morphology, neuroanatomy and genes in humans and other primates.

    PubMed

    Stanyon, Roscoe; Bigoni, Francesca

    2014-10-14

    Explaining human evolution means developing hypotheses about the occurrence of sex differences in the brain. Neuroanatomy is significantly influenced by sexual selection, involving the cognitive domain through competition for mates and mate choice. Male neuroanatomy emphasizes subcortical brain areas and visual-spatial skills whereas that of females emphasizes the neocortex and social cognitive areas. In primate species with high degrees of male competition, areas of the brain dealing with aggression are emphasized. Females have higher mirror neuron activity scores than males. Hundreds of genes differ in expression profiles between males and females. Sexually selected differences in gene expression can produce neuroanatomical sex differences. A feedback system links genes, gene expression, hormones, morphology, social structure and behavior. Sex differences, often through female choice, can be rapidly modulated by socialization. Human evolution is a dramatic case of how a trend toward pair bonding and monogamy lowered male competition and increased female choice as a necessary step in releasing the cognitive potential of our species. PMID:25445181

  4. Three-dimensional human facial morphologies as robust aging markers

    PubMed Central

    Chen, Weiyang; Qian, Wei; Wu, Gang; Chen, Weizhong; Xian, Bo; Chen, Xingwei; Cao, Yaqiang; Green, Christopher D; Zhao, Fanghong; Tang, Kun; Han, Jing-Dong J

    2015-01-01

    Aging is associated with many complex diseases. Reliable prediction of the aging process is important for assessing the risks of aging-associated diseases. However, despite intense research, so far there is no reliable aging marker. Here we addressed this problem by examining whether human 3D facial imaging features could be used as reliable aging markers. We collected > 300 3D human facial images and blood profiles well-distributed across ages of 17 to 77 years. By analyzing the morphological profiles, we generated the first comprehensive map of the aging human facial phenome. We identified quantitative facial features, such as eye slopes, highly associated with age. We constructed a robust age predictor and found that on average people of the same chronological age differ by ± 6 years in facial age, with the deviations increasing after age 40. Using this predictor, we identified slow and fast agers that are significantly supported by levels of health indicators. Despite a close relationship between facial morphological features and health indicators in the blood, facial features are more reliable aging biomarkers than blood profiles and can better reflect the general health status than chronological age. PMID:25828530

  5. Three-dimensional human facial morphologies as robust aging markers.

    PubMed

    Chen, Weiyang; Qian, Wei; Wu, Gang; Chen, Weizhong; Xian, Bo; Chen, Xingwei; Cao, Yaqiang; Green, Christopher D; Zhao, Fanghong; Tang, Kun; Han, Jing-Dong J

    2015-05-01

    Aging is associated with many complex diseases. Reliable prediction of the aging process is important for assessing the risks of aging-associated diseases. However, despite intense research, so far there is no reliable aging marker. Here we addressed this problem by examining whether human 3D facial imaging features could be used as reliable aging markers. We collected > 300 3D human facial images and blood profiles well-distributed across ages of 17 to 77 years. By analyzing the morphological profiles, we generated the first comprehensive map of the aging human facial phenome. We identified quantitative facial features, such as eye slopes, highly associated with age. We constructed a robust age predictor and found that on average people of the same chronological age differ by ± 6 years in facial age, with the deviations increasing after age 40. Using this predictor, we identified slow and fast agers that are significantly supported by levels of health indicators. Despite a close relationship between facial morphological features and health indicators in the blood, facial features are more reliable aging biomarkers than blood profiles and can better reflect the general health status than chronological age. PMID:25828530

  6. Metabolic costs and evolutionary implications of human brain development

    PubMed Central

    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

  7. The Relationship between Social Defiance, Vindictiveness, Anger, and Brain Morphology in Eight-Year-Old Boys and Girls

    ERIC Educational Resources Information Center

    Fahim, Cherine; Fiori, Marina; Evans, Alan C.; Perusse, Daniel

    2012-01-01

    The goal of this study is twofold: (1) to assess brain anatomical differences between children meeting diagnostic criteria for oppositional defiant disorder (ODD) and healthy controls, and (2) to investigate whether morphological brain characteristics associated with ODD differ in boys and girls. Eight-year-old participants (N = 38) were scanned…

  8. General Anesthesia and Human Brain Connectivity

    PubMed Central

    2012-01-01

    Abstract General anesthesia consists of amnesia, hypnosis, analgesia, and areflexia. Of these, the mechanism of hypnosis, or loss of consciousness, has been the most elusive, yet a fascinating problem. How anesthetic agents suppress human consciousness has been investigated with neuroimaging for two decades. Anesthetics substantially reduce the global cerebral metabolic rate and blood flow with a degree of regional heterogeneity characteristic to the anesthetic agent. The thalamus appears to be a common site of modulation by several anesthetics, but this may be secondary to cortical effects. Stimulus-dependent brain activation is preserved in primary sensory areas, suggesting that unconsciousness cannot be explained by cortical deafferentation or a diminution of cortical sensory reactivity. The effect of general anesthetics in functional and effective connectivity is varied depending on the agent, dose, and network studied. At an anesthetic depth characterized by the subjects' unresponsiveness, a partial, but not complete, reduction in connectivity is generally observed. Functional connectivity of the frontoparietal association cortex is often reduced, but a causal role of this change for the loss of consciousness remains uncertain. Functional connectivity of the nonspecific (intralaminar) thalamic nuclei is preferentially reduced by propofol. Higher-order thalamocortical connectivity is also reduced with certain anesthetics. The changes in functional connectivity during anesthesia induction and emergence do not mirror each other; the recovery from anesthesia may involve increases in functional connectivity above the normal wakeful baseline. Anesthetic loss of consciousness is not a block of corticofugal information transfer, but a disruption of higher-order cortical information integration. The prime candidates for functional networks of the forebrain that play a critical role in maintaining the state of consciousness are those based on the posterior parietal

  9. Alcohol-Related Brain Damage in Humans

    PubMed Central

    Erdozain, Amaia M.; Morentin, Benito; Bedford, Lynn; King, Emma; Tooth, David; Brewer, Charlotte; Wayne, Declan; Johnson, Laura; Gerdes, Henry K.; Wigmore, Peter; Callado, Luis F.; Carter, Wayne G.

    2014-01-01

    Chronic excessive alcohol intoxications evoke cumulative damage to tissues and organs. We examined prefrontal cortex (Brodmann’s area (BA) 9) from 20 human alcoholics and 20 age, gender, and postmortem delay matched control subjects. H & E staining and light microscopy of prefrontal cortex tissue revealed a reduction in the levels of cytoskeleton surrounding the nuclei of cortical and subcortical neurons, and a disruption of subcortical neuron patterning in alcoholic subjects. BA 9 tissue homogenisation and one dimensional polyacrylamide gel electrophoresis (PAGE) proteomics of cytosolic proteins identified dramatic reductions in the protein levels of spectrin β II, and α- and β-tubulins in alcoholics, and these were validated and quantitated by Western blotting. We detected a significant increase in α-tubulin acetylation in alcoholics, a non-significant increase in isoaspartate protein damage, but a significant increase in protein isoaspartyl methyltransferase protein levels, the enzyme that triggers isoaspartate damage repair in vivo. There was also a significant reduction in proteasome activity in alcoholics. One dimensional PAGE of membrane-enriched fractions detected a reduction in β-spectrin protein levels, and a significant increase in transmembranous α3 (catalytic) subunit of the Na+,K+-ATPase in alcoholic subjects. However, control subjects retained stable oligomeric forms of α-subunit that were diminished in alcoholics. In alcoholics, significant loss of cytosolic α- and β-tubulins were also seen in caudate nucleus, hippocampus and cerebellum, but to different levels, indicative of brain regional susceptibility to alcohol-related damage. Collectively, these protein changes provide a molecular basis for some of the neuronal and behavioural abnormalities attributed to alcoholics. PMID:24699688

  10. Reconstituting a human brain in animals: a Jewish perspective on human sanctity.

    PubMed

    Loike, John D; Tendler, Moshe

    2008-12-01

    The potential use of stem cells in the treatment of a variety of human diseases has been a major driving force for embryonic stem cell research. Another productive area of research has been the use of human stem cells to reconstitute human organ systems in animals in an attempt to create new animal models for human diseases. However, the possibility of transplanting human embryonic brain cells or precursor brain cells into an animal fetus presents numerous ethical challenges. This paper examines, from a Jewish perspective on human dignity, several bioethical concerns related to the reconstitution of animal brains with human neurons. PMID:19143409

  11. Resonance of human brain under head acceleration

    PubMed Central

    Laksari, Kaveh; Wu, Lyndia C.; Kurt, Mehmet; Kuo, Calvin; Camarillo, David C.

    2015-01-01

    Although safety standards have reduced fatal head trauma due to single severe head impacts, mild trauma from repeated head exposures may carry risks of long-term chronic changes in the brain's function and structure. To study the physical sensitivities of the brain to mild head impacts, we developed the first dynamic model of the skull–brain based on in vivo MRI data. We showed that the motion of the brain can be described by a rigid-body with constrained kinematics. We further demonstrated that skull–brain dynamics can be approximated by an under-damped system with a low-frequency resonance at around 15 Hz. Furthermore, from our previous field measurements, we found that head motions in a variety of activities, including contact sports, show a primary frequency of less than 20 Hz. This implies that typical head exposures may drive the brain dangerously close to its mechanical resonance and lead to amplified brain–skull relative motions. Our results suggest a possible cause for mild brain trauma, which could occur due to repetitive low-acceleration head oscillations in a variety of recreational and occupational activities. PMID:26063824

  12. [Brain evolution of the human from the paleoneurologic viewpoint].

    PubMed

    Brandt, M

    1993-12-01

    Paleoneurology interprets natural or artificial endocasts. It is, therefore, the only method which is able to provide direct information on the ancestry of the human brain. Australopithecus, Homo habilis and Homo erectus are of outstanding importance concerning human evolution. This short review deals with some well-preserved endocasts of these forms. Possibilities and limitations of paleoneurology are discussed with respect to the taxonomic attribution of fossil specimens. Functional aspects of the cortical sulcus pattern can be interpreted rather strictly and is, therefore, of considerably phylogenetic significance. It indicates that even some early hominids exhibit a human-like brain organization (e.g. KNM-ER 1470) while others (such a KNM-ER 1805) feature a rather pongid-like brain organization. However, controversy over the interpretation of endocasts from early hominids continues: It has not been possible to unequivocally demonstrate a human-like feature of the Australopithecus brain. PMID:8285598

  13. Sex beyond the genitalia: The human brain mosaic

    PubMed Central

    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

  14. Genetic Changes Shaping the Human Brain

    PubMed Central

    Bae, Byoung-il; Jayaraman, Divya; Walsh, Christopher A.

    2015-01-01

    Summary The development and function of our brain are governed by a genetic blueprint, which reflects dynamic changes over the history of evolution. Recent progress in genetics and genomics, facilitated by next-generation sequencing and single-cell sorting, has identified numerous genomic loci that are associated with a neuroanatomical or neurobehavioral phenotype. Here, we review some of the genetic changes in both protein-coding and noncoding regions that affect brain development and evolution, as well as recent progress in brain transcriptomics. Understanding these genetic changes may provide novel insights into neurological and neuropsychiatric disorders, such as autism and schizophrenia. PMID:25710529

  15. Reflectance Diffuse Optical Tomography: Its Application to Human Brain Mapping

    NASA Astrophysics Data System (ADS)

    Ueda, Yukio; Yamanaka, Takeshi; Yamashita, Daisuke; Suzuki, Toshihiko; Ohmae, Etsuko; Oda, Motoki; Yamashita, Yutaka

    2005-09-01

    We report the successful application of reflectance diffuse optical tomography (DOT) using near-infrared light with the new reconstruction algorithm that we developed to the observation of regional hemodynamic changes in the brain under specific mental tasks. Our results reveal the heterogeneous distribution of oxyhemoglobin and deoxyhemoglobin in the brain, showing complementary images of oxyhemoglobin and deoxyhemoglobin changes in certain regions. We conclude that our reflectance DOT has practical potential for human brain mapping, as well as in the diagnostic imaging of brain diseases.

  16. Optogenetic control of human neurons in organotypic brain cultures.

    PubMed

    Andersson, My; Avaliani, Natalia; Svensson, Andreas; Wickham, Jenny; Pinborg, Lars H; Jespersen, Bo; Christiansen, Søren H; Bengzon, Johan; Woldbye, David P D; Kokaia, Merab

    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. PMID:27098488

  17. Optogenetic control of human neurons in organotypic brain cultures

    PubMed Central

    Andersson, My; Avaliani, Natalia; Svensson, Andreas; Wickham, Jenny; Pinborg, Lars H.; Jespersen, Bo; Christiansen, Søren H.; Bengzon, Johan; Woldbye, David P.D.; Kokaia, Merab

    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. PMID:27098488

  18. Overview of the human brain as a distributed computing network

    SciTech Connect

    Gevins, A.S.

    1983-01-01

    The hierarchically organized human brain is viewed as a prime example of a massively parallel, adaptive information processing and process control system. A brief overview of the human brain is provided for computer architects, in hopes that the principles of massive parallelism, dense connectivity and self-organization of assemblies of processing elements will prove relevant to the design of fifth generation VLSI computing networks. 6 references.

  19. A neuronal morphologic type unique to humans and great apes

    PubMed Central

    Nimchinsky, Esther A.; Gilissen, Emmanuel; Allman, John M.; Perl, Daniel P.; Erwin, Joseph M.; Hof, Patrick R.

    1999-01-01

    We report the existence and distribution of an unusual type of projection neuron, a large, spindle-shaped cell, in layer Vb of the anterior cingulate cortex of pongids and hominids. These spindle cells were not observed in any other primate species or any other mammalian taxa, and their volume was correlated with brain volume residuals, a measure of encephalization in higher primates. These observations are of particular interest when considering primate neocortical evolution, as they reveal possible adaptive changes and functional modifications over the last 15–20 million years in the anterior cingulate cortex, a region that plays a major role in the regulation of many aspects of autonomic function and of certain cognitive processes. That in humans these unique neurons have been shown previously to be severely affected in the degenerative process of Alzheimer’s disease suggests that some of the differential neuronal susceptibility that occurs in the human brain in the course of age-related dementing illnesses may have appeared only recently during primate evolution. PMID:10220455

  20. Understanding complexity in the human brain

    PubMed Central

    Bassett, Danielle S.; Gazzaniga, Michael S.

    2011-01-01

    Although the ultimate aim of neuroscientific enquiry is to gain an understanding of the brain and how its workings relate to the mind, the majority of current efforts are largely focused on small questions using increasingly detailed data. However, it might be possible to successfully address the larger question of mind–brain mechanisms if the cumulative findings from these neuroscientific studies are coupled with complementary approaches from physics and philosophy. The brain, we argue, can be understood as a complex system or network, in which mental states emerge from the interaction between multiple physical and functional levels. Achieving further conceptual progress will crucially depend on broad-scale discussions regarding the properties of cognition and the tools that are currently available or must be developed in order to study mind–brain mechanisms. PMID:21497128

  1. Fuzzy scaling analysis of a mouse mutant with brain morphological changes.

    PubMed

    Pham, Tuan D; Müller, Catharina C; Crane, Denis I

    2009-07-01

    Scaling behavior inherently exists in fundamental biological structures, and the measure of such an attribute can only be known at a given scale of observation. Thus, the properties of fractals and power-law scaling have become attractive for research in biology and medicine because of their potential for discovering patterns and characteristics of complex biological morphologies. Despite the successful applications of fractals for the life sciences, the quantitative measure of the scale invariance expressed by fractal dimensions is limited in more complex situations, such as for histopathological analysis of tissue changes in disease. In this paper, we introduce the concept of fuzzy scaling and its analysis of a mouse mutant with postnatal brain morphological changes. PMID:19369166

  2. Catecholaminergic Gene Polymorphisms Are Associated with GI Symptoms and Morphological Brain Changes in Irritable Bowel Syndrome

    PubMed Central

    Shih, Wendy; Presson, Angela P.; Hammer, Christian; Niesler, Beate; Heendeniya, Nuwanthi; Mayer, Emeran A.; Chang, Lin

    2015-01-01

    Background Genetic and environmental factors contribute to the pathophysiology of irritable bowel syndrome (IBS). In particular, early adverse life events (EALs) and the catecholaminergic system have been implicated. Aims To investigate whether catecholaminergic SNPs with or without interacting with EALs are associated with: 1) a diagnosis of IBS, 2) IBS symptoms and 3) morphological alterations in brain regions associated with somatosensory, viscerosensory, and interoceptive processes. Methods In 277 IBS and 382 healthy control subjects (HCs), 11 SNPs in genes of the catecholaminergic signaling pathway were genotyped. A subset (121 IBS, 209 HCs) underwent structural brain imaging (magnetic resonance imaging [MRI]). Logistic and linear regressions evaluated each SNP separately and their interactions with EALs in predicting IBS and GI symptom severity, respectively. General linear models determined grey matter (GM) alterations from the SNPs and EALs that were predictive of IBS. Results 1) Diagnosis: There were no statistically significant associations between the SNPs and IBS status with or without the interaction with EAL after adjusting for multiple comparisons. 2) Symptoms: GI symptom severity was associated with ADRA1D rs1556832 (P = 0.010). 3) Brain morphometry: In IBS, the homozygous genotype of the major ADRA1D allele was associated with GM increases in somatosensory regions (FDR q = 0.022), left precentral gyrus (q = 0.045), and right hippocampus (q = 0.009). In individuals with increasing sexual abuse scores, the ADRAβ2 SNP was associated with GM changes in the left posterior insula (q = 0.004) and left putamen volume (q = 0.029). Conclusion In IBS, catecholaminergic SNPs are associated with symptom severity and morphological changes in brain regions concerned with sensory processing and modulation and affect regulation. Thus, certain adrenergic receptor genes may facilitate or worsen IBS symptoms. PMID:26288143

  3. Near infrared Raman spectra of human brain lipids

    NASA Astrophysics Data System (ADS)

    Krafft, Christoph; Neudert, Lars; Simat, Thomas; Salzer, Reiner

    2005-05-01

    Human brain tissue, in particular white matter, contains high lipid content. These brain lipids can be divided into three principal classes: neutral lipids including the steroid cholesterol, phospholipids and sphingolipids. Major lipids in normal human brain tissue are phosphatidylcholine, phosphatidylethanolamine, phosphatidylserine, phosphatidylinositol, phosphatidic acid, sphingomyelin, galactocerebrosides, gangliosides, sulfatides and cholesterol. Minor lipids are cholesterolester and triacylglycerides. During transformation from normal brain tissue to tumors, composition and concentration of lipids change in a specific way. Therefore, analysis of lipids might be used as a diagnostic parameter to distinguish normal tissue from tumors and to determine the tumor type and tumor grade. Raman spectroscopy has been suggested as an analytical tool to detect these changes even under intra-operative conditions. We recorded Raman spectra of the 12 major and minor brain lipids with 785 nm excitation in order to identify their spectral fingerprints for qualitative and quantitative analyses.

  4. Why Our Kids Can Write; or, Running Slo's through the Right Brain Equals the Morphology of Diddley Doos.

    ERIC Educational Resources Information Center

    Palmer, Thelma

    1980-01-01

    Proposes that offering students activities that exercise right-brain functions (nonverbal, nonrational, spatial, and intuitive) helps students become more fully developed human beings and better writers. (RL)

  5. Do glutathione levels decline in aging human brain?

    PubMed

    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. PMID:26845616

  6. Effects of Habitat and Social Complexity on Brain Size, Brain Asymmetry and Dentate Gyrus Morphology in Two Octodontid Rodents.

    PubMed

    Sobrero, Raúl; Fernández-Aburto, Pedro; Ly-Prieto, Álvaro; Delgado, Scarlett E; Mpodozis, Jorge; Ebensperger, Luis A

    2016-01-01

    Navigational and social challenges due to habitat conditions and sociality are known to influence dentate gyrus (DG) morphology, yet the relative importance of these factors remains unclear. Thus, we studied three natural populations of O. lunatus (Los Molles) and Octodon degus (El Salitre and Rinconada), two caviomorph species that differ in the extent of sociality and with contrasting vegetation cover of habitat used. The brains and DG of male and female breeding degus with simultaneous information on their physical and social environments were examined. The extent of sociality was quantified from total group size and range area overlap. O. degus at El Salitre was more social than at Rinconada and than O. lunatus from Los Molles. The use of transects to quantify cover of vegetation (and other physical objects in the habitat) and measures of the spatial behavior of animals indicated animal navigation based on unique cues or global landmarks is more cognitively challenging to O. lunatus. During lactation, female O. lunatus had larger brains than males. Relative DG volume was similar across sexes and populations. The right hemisphere of male and female O. lunatus had more cells than the left hemisphere, with DG directional asymmetry not found in O. degus. Degu population differences in brain size and DG cell number seemed more responsive to differences in habitat than to differences in sociality. Yet, large-sized O. degus (but not O. lunatus) that ranged over larger areas and were members of larger social groups had more DG cells per hemisphere. Thus, within-population variation in DG cell number by hemisphere was consistent with a joint influence of habitat and sociality in O. degus at El Salitre. PMID:27045373

  7. Evolution of the human brain: when bigger is better

    PubMed Central

    Hofman, Michel A.

    2014-01-01

    Comparative studies of the brain in mammals suggest that there are general architectural principles governing its growth and evolutionary development. We are beginning to understand the geometric, biophysical and energy constraints that have governed the evolution and functional organization of the brain and its underlying neuronal network. The object of this review is to present current perspectives on primate brain evolution, especially in humans, and to examine some hypothetical organizing principles that underlie the brain's complex organization. Some of the design principles and operational modes that underlie the information processing capacity of the cerebral cortex in primates will be explored. It is shown that the development of the cortex coordinates folding with connectivity in a way that produces smaller and faster brains, then otherwise would have been possible. In view of the central importance placed on brain evolution in explaining the success of our own species, one may wonder whether there are physical limits that constrain its processing power and evolutionary potential. It will be argued that at a brain size of about 3500 cm3, corresponding to a brain volume two to three times that of modern man, the brain seems to reach its maximum processing capacity. The larger the brain grows beyond this critical size, the less efficient it will become, thus limiting any improvement in cognitive power. PMID:24723857

  8. Conscious Brain-to-Brain Communication in Humans Using Non-Invasive Technologies

    PubMed Central

    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. PMID:25137064

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

    PubMed

    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. PMID:25137064

  10. Human brain activity with functional NIR optical imager

    NASA Astrophysics Data System (ADS)

    Luo, Qingming

    2001-08-01

    In this paper we reviewed the applications of functional near infrared optical imager in human brain activity. Optical imaging results of brain activity, including memory for new association, emotional thinking, mental arithmetic, pattern recognition ' where's Waldo?, occipital cortex in visual stimulation, and motor cortex in finger tapping, are demonstrated. It is shown that the NIR optical method opens up new fields of study of the human population, in adults under conditions of simulated or real stress that may have important effects upon functional performance. It makes practical and affordable for large populations the complex technology of measuring brain function. It is portable and low cost. In cognitive tasks subjects could report orally. The temporal resolution could be millisecond or less in theory. NIR method will have good prospects in exploring human brain secret.

  11. Morphological variation in great ape and modern human mandibles.

    PubMed

    Humphrey, L T; Dean, M C; Stringer, C B

    1999-11-01

    Adult mandibles of 317 modern humans and 91 great apes were selected that showed no pathology. Adult mandibles of Pan troglodytes troglodytes, Pongo pygmaeus pygmaeus and Gorilla gorilla gorilla and from 2 modern human populations (Zulu and Europeans from Spitalfields) were reliably sexed. Thirteen measurements were defined and included mandibular height, length and breadth in representative positions. Univariate statistical techniques and multivariate (principal component analysis and discriminant analysis) statistical techniques were used to investigate interspecific variability and sexual dimorphism in human and great ape mandibles, and intraspecific variability among the modern human mandibles. Analysis of interspecific differences revealed some pairs of variables with a tight linear relationship and others where Homo and the great apes pulled apart from one another due to shape differences. Homo and Pan are least sexually dimorphic in the mandible, Pan less so than Homo sapiens, but both the magnitude of sexual dimorphism and the distribution of sexually dimorphic measurements varied both among and between modern humans and great apes. Intraspecific variation among the 10 populations of modern humans was less than that generally reported in studies of crania (74.3% of mandibles were correctly classified into 1 of 10 populations using discriminant functions based on 13 variables as compared with 93% of crania from 17 populations based on 70 variables in one extensive study of crania). A subrecent European population (Poundbury) emerged as more different from a recent European population (Spitalfields) than other more diverse modern populations were from each other, suggesting considerable morphological plasticity in the mandible through time. This study forms a sound basis on which to explore mandibular variation in Neanderthals, early Homo sapiens and other more ancient fossil hominids. PMID:10634689

  12. BrainKnowledge: a human brain function mapping knowledge-base system.

    PubMed

    Hsiao, Mei-Yu; Chen, Chien-Chung; Chen, Jyh-Horng

    2011-03-01

    Associating fMRI image datasets with the available literature is crucial for the analysis and interpretation of fMRI data. Here, we present a human brain function mapping knowledge-base system (BrainKnowledge) that associates fMRI data analysis and literature search functions. BrainKnowledge not only contains indexed literature, but also provides the ability to compare experimental data with those derived from the literature. BrainKnowledge provides three major functions: (1) to search for brain activation models by selecting a particular brain function; (2) to query functions by brain structure; (3) to compare the fMRI data with data extracted from the literature. All these functions are based on our literature extraction and mining module developed earlier (Hsiao, Chen, Chen. Journal of Biomedical Informatics 42, 912-922, 2009), which automatically downloads and extracts information from a vast amount of fMRI literature and generates co-occurrence models and brain association patterns to illustrate the relevance of brain structures and functions. BrainKnowledge currently provides three co-occurrence models: (1) a structure-to-function co-occurrence model; (2) a function-to-structure co-occurrence model; and (3) a brain structure co-occurrence model. Each model has been generated from over 15,000 extracted Medline abstracts. In this study, we illustrate the capabilities of BrainKnowledge and provide an application example with the studies of affect. BrainKnowledge, which combines fMRI experimental results with Medline abstracts, may be of great assistance to scientists not only by freeing up resources and valuable time, but also by providing a powerful tool that collects and organizes over ten thousand abstracts into readily usable and relevant sources of information for researchers. PMID:20857233

  13. Modulative effects of COMT haplotype on age-related associations with brain morphology.

    PubMed

    Lee, Annie; Qiu, Anqi

    2016-06-01

    Catechol-O-methyltransferase (COMT), located on chromosome 22q11.2, encodes an enzyme critical for dopamine flux in the prefrontal cortex. Genetic variants of COMT have been suggested to functionally manipulate prefrontal morphology and function in healthy adults. This study aims to investigate modulative roles of individuals COMT SNPs (rs737865, val158met, rs165599) and its haplotypes in age-related brain morphology using an Asian sample with 174 adults aged from 21 to 80 years. We showed an age-related decline in cortical thickness of the dorsal visual pathway, including the left dorsolateral prefrontal cortex, bilateral angular gyrus, right superior frontal cortex, and age-related shape compression in the basal ganglia as a function of the genotypes of the individual COMT SNPs, especially COMT val158met. Using haplotype trend regression analysis, COMT haplotype probabilities were estimated and further revealed an age-related decline in cortical thickness in the default mode network (DMN), including the posterior cingulate, precuneus, supramarginal and paracentral cortex, and the ventral visual system, including the occipital cortex and left inferior temporal cortex, as a function of the COMT haplotype. Our results provided new evidence on an antagonistic pleiotropic effect in COMT, suggesting that genetically programmed neural benefits in early life may have a potential bearing towards neural susceptibility in later life. Hum Brain Mapp 37:2068-2082, 2016. © 2016 Wiley Periodicals, Inc. PMID:26920810

  14. Electrophysiological Correlates of Morphological Neuroplasticity in Human Callosal Dysgenesis

    PubMed Central

    Lazarev, Vladimir V.; de Carvalho Monteiro, Myriam; Vianna-Barbosa, Rodrigo; deAzevedo, Leonardo C.; Lent, Roberto; Tovar-Moll, Fernanda

    2016-01-01

    In search for the functional counterpart of the alternative Probst and sigmoid bundles, considered as morphological evidence of neuroplasticity in callosal dysgenesis, electroencephalographic (EEG) coherence analysis was combined with high resolution and diffusion tensor magnetic resonance imaging. Data of two patients with callosal agenesis, plus two with typical partial dysgenesis with a remnant genu, and one atypical patient with a substantially reduced genu were compared to those of fifteen neurotypic controls. The interhemispheric EEG coherence between homologous nontemporal brain regions corresponded to absence or partial presence of callosal connections. A generalized coherence reduction was observed in complete acallosal patients, as well as coherence preservation in the anterior areas of the two patients with a remnant genu. jThe sigmoid bundles found in three patients with partial dysgenesis correlated with augmented EEG coherence between anterior regions of one hemisphere and posterior regions of the other. These heterologous (crossed) interhemispheric connections were asymmetric in both imaging and EEG patterns, with predominance of the right-anterior-to-left-posterior connections over the mirror ones. The Probst bundles correlated with higher intrahemispheric long-distance coherence in all patients. The significant correlations observed for the delta, theta and alpha bands indicate that these alternative pathways are functional, although the neuropsychological nature of this function is still unknown. PMID:27055255

  15. Isolation and characterization of human malignant glioma cells from histologically normal brain.

    PubMed

    Silbergeld, D L; Chicoine, M R

    1997-03-01

    Brain invasion prevents complete surgical extirpation of malignant gliomas; however, invasive cells from distant, histologically normal brain previously have not been isolated, cultured, and characterized. To evaluate invasive human malignant glioma cells, the authors established cultures from gross tumor and histologically normal brain. Three men and one woman, with a mean age of 67 years, underwent two frontal and two temporal lobectomies for tumors, which yielded specimens of both gross tumor and histologically normal brain. Each specimen was acquired a minimum of 4 cm from the gross tumor. The specimens were split: a portion was sent for neuropathological evaluation (three glioblastomas multiforme and one oligodendroglioma) and a portion was used to establish cell lines. Morphologically, the specimens of gross tumor and histologically normal brain were identical in three of the four cell culture pairs. Histochemical staining characteristics were consistent both within each pair and when compared with the specimens sent for neuropathological evaluation. Cultures demonstrated anchorage-independent growth in soft agarose and neoplastic karyotypes. Growth rates in culture were greater for histologically normal brain than for gross tumor in three of the four culture pairs. Although the observed increases in growth rates of histologically normal brain cultures do not correlate with in vivo behavior, these findings corroborate the previously reported stem cell potential of invasive glioma cells. Using the radial dish assay, no significant differences in motility between cultures of gross tumor and histologically normal brain were found. In summary, tumor cells were cultured from histologically normal brain acquired from a distance greater than 4 cm from the gross tumor, indicating the relative insensitivity of standard histopathological identification of invasive glioma cells (and hence the inadequacy of frozen-section evaluation of resection margins). Cell lines

  16. Insights into Brain Glycogen Metabolism: THE STRUCTURE OF HUMAN BRAIN GLYCOGEN PHOSPHORYLASE.

    PubMed

    Mathieu, Cécile; de la Sierra-Gallay, Ines Li; Duval, Romain; Xu, Ximing; Cocaign, Angélique; Léger, Thibaut; Woffendin, Gary; Camadro, Jean-Michel; Etchebest, Catherine; Haouz, Ahmed; Dupret, Jean-Marie; Rodrigues-Lima, Fernando

    2016-08-26

    Brain glycogen metabolism plays a critical role in major brain functions such as learning or memory consolidation. However, alteration of glycogen metabolism and glycogen accumulation in the brain contributes to neurodegeneration as observed in Lafora disease. Glycogen phosphorylase (GP), a key enzyme in glycogen metabolism, catalyzes the rate-limiting step of glycogen mobilization. Moreover, the allosteric regulation of the three GP isozymes (muscle, liver, and brain) by metabolites and phosphorylation, in response to hormonal signaling, fine-tunes glycogenolysis to fulfill energetic and metabolic requirements. Whereas the structures of muscle and liver GPs have been known for decades, the structure of brain GP (bGP) has remained elusive despite its critical role in brain glycogen metabolism. Here, we report the crystal structure of human bGP in complex with PEG 400 (2.5 Å) and in complex with its allosteric activator AMP (3.4 Å). These structures demonstrate that bGP has a closer structural relationship with muscle GP, which is also activated by AMP, contrary to liver GP, which is not. Importantly, despite the structural similarities between human bGP and the two other mammalian isozymes, the bGP structures reveal molecular features unique to the brain isozyme that provide a deeper understanding of the differences in the activation properties of these allosteric enzymes by the allosteric effector AMP. Overall, our study further supports that the distinct structural and regulatory properties of GP isozymes contribute to the different functions of muscle, liver, and brain glycogen. PMID:27402852

  17. Mitochondrial viability in mouse and human postmortem brain

    PubMed Central

    Barksdale, Keri A.; Perez-Costas, Emma; Gandy, Johanna C.; Melendez-Ferro, Miguel; Roberts, Rosalinda C.; Bijur, Gautam N.

    2010-01-01

    Neuronal function in the brain requires energy in the form of ATP, and mitochondria are canonically associated with ATP production in neurons. The electrochemical gradient, which underlies the mitochondrial transmembrane potential (ΔΨmem), is harnessed for ATP generation. Here we show that ΔΨmem and ATP-production can be engaged in mitochondria isolated from human brains up to 8.5 h postmortem. Also, a time course of postmortem intervals from 0 to 24 h using mitochondria isolated from mouse cortex reveals that ΔΨmem in mitochondria can be reconstituted beyond 10 h postmortem. It was found that complex I of the mitochondrial electron transport chain was affected adversely with increasing postmortem intervals. Mitochondria isolated from postmortem mouse brains maintain the ability to produce ATP, but rates of production decreased with longer postmortem intervals. Furthermore, we show that postmortem brain mitochondria retain their ΔΨmem and ATP-production capacities following cryopreservation. Our finding that ΔΨmem and ATP-generating capacity can be reinitiated in brain mitochondria hours after death indicates that human postmortem brains can be an abundant source of viable mitochondria to study metabolic processes in health and disease. It is also possible to archive these mitochondria for future studies.—Barksdale, K. A., Perez-Costas, E., Gandy, J. C., Melendez-Ferro, M., Roberts, R. C., Bijur, G. N. Mitochondrial viability in mouse and human postmortem brain. PMID:20466876

  18. Progress on the paternal brain: theory, animal models, human brain research, and mental health implications.

    PubMed

    Swain, J E; Dayton, C J; Kim, P; Tolman, R M; Volling, B L

    2014-01-01

    With a secure foundation in basic research across mammalian species in which fathers participate in the raising of young, novel brain-imaging approaches are outlining a set of consistent brain circuits that regulate paternal thoughts and behaviors in humans. The newest experimental paradigms include increasingly realistic baby-stimuli to provoke paternal cognitions and behaviors with coordinated hormone measures to outline brain networks that regulate motivation, reflexive caring, emotion regulation, and social brain networks with differences and similarities to those found in mothers. In this article, on the father brain, we review all brain-imaging studies on PubMed to date on the human father brain and introduce the topic with a selection of theoretical models and foundational neurohormonal research on animal models in support of the human work. We discuss potentially translatable models for the identification and treatment of paternal mood and father-child relational problems, which could improve infant mental health and developmental trajectories with potentially broad public health importance. PMID:25798491

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

    PubMed Central

    Kirsch, Lior; Chechik, Gal

    2016-01-01

    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. PMID:27564987

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

    PubMed

    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/). PMID:23861951

  1. TV, Brain Waves and Human Behavior

    ERIC Educational Resources Information Center

    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)

  2. Human and rat brain lipofuscin proteome

    Technology Transfer Automated Retrieval System (TEKTRAN)

    The accumulation of an autofluorescent pigment called lipofuscin in neurons is an invariable hallmark of brain aging. So far, this material has been considered to be waste material without particular relevance for cellular pathology. However, two lines of evidence argue that lipofuscin may have yet ...

  3. Development of Human Brain Structural Networks Through Infancy and Childhood

    PubMed Central

    Huang, Hao; Shu, Ni; Mishra, Virendra; Jeon, Tina; Chalak, Lina; Wang, Zhiyue J.; Rollins, Nancy; Gong, Gaolang; Cheng, Hua; Peng, Yun; Dong, Qi; He, Yong

    2015-01-01

    During human brain development through infancy and childhood, microstructural and macrostructural changes take place to reshape the brain's structural networks and better adapt them to sophisticated functional and cognitive requirements. However, structural topological configuration of the human brain during this specific development period is not well understood. In this study, diffusion magnetic resonance image (dMRI) of 25 neonates, 13 toddlers, and 25 preadolescents were acquired to characterize network dynamics at these 3 landmark cross-sectional ages during early childhood. dMRI tractography was used to construct human brain structural networks, and the underlying topological properties were quantified by graph-theory approaches. Modular organization and small-world attributes are evident at birth with several important topological metrics increasing monotonically during development. Most significant increases of regional nodes occur in the posterior cingulate cortex, which plays a pivotal role in the functional default mode network. Positive correlations exist between nodal efficiencies and fractional anisotropy of the white matter traced from these nodes, while correlation slopes vary among the brain regions. These results reveal substantial topological reorganization of human brain structural networks through infancy and childhood, which is likely to be the outcome of both heterogeneous strengthening of the major white matter tracts and pruning of other axonal fibers. PMID:24335033

  4. Language Impairments in ASD Resulting from a Failed Domestication of the Human Brain.

    PubMed

    Benítez-Burraco, Antonio; Lattanzi, Wanda; Murphy, Elliot

    2016-01-01

    Autism spectrum disorders (ASD) are pervasive neurodevelopmental disorders entailing social and cognitive deficits, including marked problems with language. Numerous genes have been associated with ASD, but it is unclear how language deficits arise from gene mutation or dysregulation. It is also unclear why ASD shows such high prevalence within human populations. Interestingly, the emergence of a modern faculty of language has been hypothesized to be linked to changes in the human brain/skull, but also to the process of self-domestication of the human species. It is our intention to show that people with ASD exhibit less marked domesticated traits at the morphological, physiological, and behavioral levels. We also discuss many ASD candidates represented among the genes known to be involved in the "domestication syndrome" (the constellation of traits exhibited by domesticated mammals, which seemingly results from the hypofunction of the neural crest) and among the set of genes involved in language function closely connected to them. Moreover, many of these genes show altered expression profiles in the brain of autists. In addition, some candidates for domestication and language-readiness show the same expression profile in people with ASD and chimps in different brain areas involved in language processing. Similarities regarding the brain oscillatory behavior of these areas can be expected too. We conclude that ASD may represent an abnormal ontogenetic itinerary for the human faculty of language resulting in part from changes in genes important for the "domestication syndrome" and, ultimately, from the normal functioning of the neural crest. PMID:27621700

  5. In vivo multiphoton tomography and fluorescence lifetime imaging of human brain tumor tissue.

    PubMed

    Kantelhardt, Sven R; Kalasauskas, Darius; König, Karsten; Kim, Ella; Weinigel, Martin; Uchugonova, Aisada; Giese, Alf

    2016-05-01

    High resolution multiphoton tomography and fluorescence lifetime imaging differentiates glioma from adjacent brain in native tissue samples ex vivo. Presently, multiphoton tomography is applied in clinical dermatology and experimentally. We here present the first application of multiphoton and fluorescence lifetime imaging for in vivo imaging on humans during a neurosurgical procedure. We used a MPTflex™ Multiphoton Laser Tomograph (JenLab, Germany). We examined cultured glioma cells in an orthotopic mouse tumor model and native human tissue samples. Finally the multiphoton tomograph was applied to provide optical biopsies during resection of a clinical case of glioblastoma. All tissues imaged by multiphoton tomography were sampled and processed for conventional histopathology. The multiphoton tomograph allowed fluorescence intensity- and fluorescence lifetime imaging with submicron spatial resolution and 200 picosecond temporal resolution. Morphological fluorescence intensity imaging and fluorescence lifetime imaging of tumor-bearing mouse brains and native human tissue samples clearly differentiated tumor and adjacent brain tissue. Intraoperative imaging was found to be technically feasible. Intraoperative image quality was comparable to ex vivo examinations. To our knowledge we here present the first intraoperative application of high resolution multiphoton tomography and fluorescence lifetime imaging of human brain tumors in situ. It allowed in vivo identification and determination of cell density of tumor tissue on a cellular and subcellular level within seconds. The technology shows the potential of rapid intraoperative identification of native glioma tissue without need for tissue processing or staining. PMID:26830089

  6. Sibling rivalry among paralogs promotes evolution of the human brain.

    PubMed

    Tyler-Smith, Chris; Xue, Yali

    2012-05-11

    Geneticists have long sought to identify the genetic changes that made us human, but pinpointing the functionally relevant changes has been challenging. Two papers in this issue suggest that partial duplication of SRGAP2, producing an incomplete protein that antagonizes the original, contributed to human brain evolution. PMID:22579279

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

    ERIC Educational Resources Information Center

    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…

  8. Genetic regulation of human brain development: lessons from Mendelian diseases

    PubMed Central

    Dixon-Salazar, Tracy J.; Gleeson, Joseph G.

    2016-01-01

    One of the fundamental goals in human genetics is to link gene function to phenotype, yet the function of the majority of the genes in the human body is still poorly understood. This is especially true for the developing human brain. The study of human phenotypes that result from inherited, mutated alleles is the most direct evidence for the requirement of a gene in human physiology. Thus, the study of Mendelian central nervous system(CNS) diseases can be an extremely powerful approach to elucidate such phenotypic/genotypic links and to increase our understanding of the key components required for development of the human brain. In this review, we highlight examples of how the study of inherited neurodevelopmental disorders contributes to our knowledge of both the “normal” and diseased human brain, as well as elaborate on the future of this type of research. Mendelian disease research has been, and will continue to be, key to understanding the molecular mechanisms that underlie human brain function, and will ultimately form a basis for the design of intelligent, mechanism-specific treatments for nervous system disorders. PMID:21062301

  9. Toward discovery science of human brain function.

    PubMed

    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

    2010-03-01

    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 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 (<0.1 Hz) fluctuations in the fMRI signal that are temporally correlated across functionally related areas. Referred to as functional connectivity, these correlations yield detailed maps of complex neural systems, collectively constituting an individual's "functional connectome." Reproducibility across datasets and individuals suggests the functional connectome has a common architecture, yet each 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, will require multicenter collaborative datasets. Here we initiate this endeavor by gathering R-fMRI data from 1,414 volunteers collected independently at 35 international centers. We demonstrate a universal architecture of positive and negative functional connections, as well as consistent loci of inter-individual variability. Age and sex emerged as significant determinants. These results demonstrate that independent R-fMRI datasets can be aggregated and shared. High-throughput R-fMRI can provide quantitative phenotypes for molecular genetic studies and biomarkers of developmental and pathological processes 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/. PMID

  10. Biomechanics of Traumatic Brain Injury: Influences of the Morphologic Heterogeneities of the Cerebral Cortex

    PubMed Central

    Gervaise, H.M.T.; van Dommelen, J.A.W.; Geers, M.G.D.

    2008-01-01

    Traumatic brain injury (TBI) can be caused by accidents and often leads to permanent health issues or even death. Brain injury criteria are used for assessing the probability of TBI, if a certain mechanical load is applied. The currently used injury criteria in the automotive industry are based on global head kinematics. New methods, based on finite element modeling, use brain injury criteria at lower scale levels, e.g., tissue-based injury criteria. However, most current computational head models lack the anatomical details of the cerebrum. To investigate the influence of the morphologic heterogeneities of the cerebral cortex, a numerical model of a representative part of the cerebral cortex with a detailed geometry has been developed. Several different geometries containing gyri and sulci have been developed for this model. Also, a homogeneous geometry has been made to analyze the relative importance of the heterogeneities. The loading conditions are based on a computational head model simulation. The results of this model indicate that the heterogeneities have an influence on the equivalent stress. The maximum equivalent stress in the heterogeneous models is increased by a factor of about 1.3–1.9 with respect to the homogeneous model, whereas the mean equivalent stress is increased by at most 10%. This implies that tissue-based injury criteria may not be accurately applied to most computational head models used nowadays, which do not account for sulci and gyri. PMID:18465248

  11. Morphological appearances of human lens epithelial cells in culture.

    PubMed

    Power, W; Neylan, D; Collum, L

    1993-01-01

    A system for culturing human lens epithelial cells in the laboratory was developed. The morphological appearances of the cells was studied using phase contrast, scanning and transmission electron microscopy. Cell marker studies using monoclonal antibodies to cytokeratin, vimentin and epithelial membrane antigen were also performed. There was a marked increase in cell size as a function of time in culture. After 3 to 4 weeks cells showed early signs of ageing. By 6 to 8 weeks the majority of the cells had become very irregular in shape and demonstrated irregularities of the plasma membrane and intra-cytoplasmic vacuole formation. The cells stained strongly for vimentin and epithelial membrane antigen. Staining with cytokeratin was somewhat weaker. This culture technique provides us with a suitable model for studying the growth behavior of these cells. PMID:7512459

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

    ERIC Educational Resources Information Center

    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…

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

    NASA Astrophysics Data System (ADS)

    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.

  14. Expectation modulates neural representations of valence throughout the human brain.

    PubMed

    Ramayya, Ashwin G; Pedisich, Isaac; Kahana, Michael J

    2015-07-15

    The brain's sensitivity to unexpected gains or losses plays an important role in our ability to learn new behaviors (Rescorla and Wagner, 1972; Sutton and Barto, 1990). Recent work suggests that gains and losses are ubiquitously encoded throughout the human brain (Vickery et al., 2011), however, the extent to which reward expectation modulates these valence representations is not known. To address this question, we analyzed recordings from 4306 intracranially implanted electrodes in 39 neurosurgical patients as they performed a two-alternative probability learning task. Using high-frequency activity (HFA, 70-200 Hz) as an indicator of local firing rates, we found that expectation modulated reward-related neural activity in widespread brain regions, including regions that receive sparse inputs from midbrain dopaminergic neurons. The strength of unexpected gain signals predicted subjects' abilities to encode stimulus-reward associations. Thus, neural signals that are functionally related to learning are widely distributed throughout the human brain. PMID:25937489

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

    SciTech Connect

    Not Available

    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.

  16. Decoding Spontaneous Emotional States in the Human Brain.

    PubMed

    Kragel, Philip A; Knodt, Annchen R; Hariri, Ahmad R; LaBar, Kevin S

    2016-09-01

    Pattern classification of human brain activity provides unique insight into the neural underpinnings of diverse mental states. These multivariate tools have recently been used within the field of affective neuroscience to classify distributed patterns of brain activation evoked during emotion induction procedures. Here we assess whether neural models developed to discriminate among distinct emotion categories exhibit predictive validity in the absence of exteroceptive emotional stimulation. In two experiments, we show that spontaneous fluctuations in human resting-state brain activity can be decoded into categories of experience delineating unique emotional states that exhibit spatiotemporal coherence, covary with individual differences in mood and personality traits, and predict on-line, self-reported feelings. These findings validate objective, brain-based models of emotion and show how emotional states dynamically emerge from the activity of separable neural systems. PMID:27627738

  17. Hemodynamic Effects of Long-term Morphological Changes in the Human Carotid Sinus

    PubMed Central

    Seong, Jaehoon; Jeong, Woowon; Smith, Nataliya; Towner, Rheal A.

    2015-01-01

    Previous investigations of morphology for human carotid artery bifurcation from infancy to young adulthood found substantial growth of the internal carotid artery with advancing age, and the development of the carotid sinus at the root of the internal carotid artery during teen age years. Although the reasons for the appearance of the carotid sinus are not clearly understood yet, it has been hypothesized that the dilation of the carotid sinus serves to support pressure sensing, and slows the blood flow to reduce pulsatility to protect the brain. In order to understand this interesting evolvement at the carotid bifurcation in the aspects of fluid mechanics, we performed in vitro phase-contrast MR flow experiments using compliant silicone replicas of age-dependent carotid artery bifurcations. The silicone models in childhood, adolescence, and adulthood were fabricated using a rapid prototyping technique, and incorporated with a bench-top flow mock circulation loop using a computer-controlled piston pump. The results of the in vitro flow study showed highly complex flow characteristics at the bifurcation in all age-dependent models. However, the highest magnitude of kinetic energy was found at the internal carotid artery in the child model. The high kinetic energy in the internal carotid artery during childhood might be one of the local hemodynamic forces that initiate morphological long-term development of the carotid sinus in the human carotid bifurcation. PMID:25702250

  18. Hemodynamic effects of long-term morphological changes in the human carotid sinus.

    PubMed

    Seong, Jaehoon; Jeong, Woowon; Smith, Nataliya; Towner, Rheal A

    2015-04-13

    Previous investigations of morphology for human carotid artery bifurcation from infancy to young adulthood found substantial growth of the internal carotid artery with advancing age, and the development of the carotid sinus at the root of the internal carotid artery during teenage years. Although the reasons for the appearance of the carotid sinus are not clearly understood yet, it has been hypothesized that the dilation of the carotid sinus serves to support pressure sensing, and slows the blood flow to reduce pulsatility to protect the brain. In order to understand this interesting evolvement at the carotid bifurcation in the aspects of fluid mechanics, we performed in vitro phase-contrast MR flow experiments using compliant silicone replicas of age-dependent carotid artery bifurcations. The silicone models in childhood, adolescence, and adulthood were fabricated using a rapid prototyping technique, and incorporated with a bench-top flow mock circulation loop using a computer-controlled piston pump. The results of the in vitro flow study showed highly complex flow characteristics at the bifurcation in all age-dependent models. However, the highest magnitude of kinetic energy was found at the internal carotid artery in the child model. The high kinetic energy in the internal carotid artery during childhood might be one of the local hemodynamic forces that initiate morphological long-term development of the carotid sinus in the human carotid bifurcation. PMID:25702250

  19. Brain Activation During Singing: "Clef de Sol Activation" Is the "Concert" of the Human Brain.

    PubMed

    Mavridis, Ioannis N; Pyrgelis, Efstratios-Stylianos

    2016-03-01

    Humans are the most complex singers in nature, and the human voice is thought by many to be the most beautiful musical instrument. Aside from spoken language, singing represents a second mode of acoustic communication in humans. The purpose of this review article is to explore the functional anatomy of the "singing" brain. Methodologically, the existing literature regarding activation of the human brain during singing was carefully reviewed, with emphasis on the anatomic localization of such activation. Relevant human studies are mainly neuroimaging studies, namely functional magnetic resonance imaging and positron emission tomography studies. Singing necessitates activation of several cortical, subcortical, cerebellar, and brainstem areas, served and coordinated by multiple neural networks. Functionally vital cortical areas of the frontal, parietal, and temporal lobes bilaterally participate in the brain's activation process during singing, confirming the latter's role in human communication. Perisylvian cortical activity of the right hemisphere seems to be the most crucial component of this activation. This also explains why aphasic patients due to left hemispheric lesions are able to sing but not speak the same words. The term clef de sol activation is proposed for this crucial perisylvian cortical activation due to the clef de sol shape of the topographical distribution of these cortical areas around the sylvian fissure. Further research is needed to explore the connectivity and sequence of how the human brain activates to sing. PMID:26966964

  20. Morphological Texture Manipulation for The Evaluation of Human Visual Sensibility

    NASA Astrophysics Data System (ADS)

    Asano, Chie Muraki; Asano, Akira; Li, Liang; Fujimoto, Takako

    Since the surface texture of materials often affects human visual impressions as much as or more than the design, shape, or color properties, texture characteristics have been studied as features of object identification. We have been investigating the effect of texture on visual impression and objective identification using black fabrics that do not exhibit any effects of color. Our studies showed that visual impressions of texture correspond to complex micro-components and global structures of image features of those textures. Our results also showed that some important elements influence human visual impressions and identification of textures. Because of a variety of fibrous structures, it is not easy to provide a systematic analysis of clothing materials. Nevertheless, developing the method and collecting data on these elements and their effects using these image features will be important. To make this research applicable for wider use, we have been studying precisely what it is about an arbitrary texture that influences human visual impressions and sensibility. As a new step, in this paper, a texture is altered and transformed using the parameter estimation method of texture based on mathematical morphology, which is often used for extracting image components that are useful for representation and description. A texture is decomposed into a primitive and grain arrangement which correspond to local and global characteristics, respectively. Different textures are created by modifying the primitive and the arrangement to investigate the effects of modifications of local and global features. The relationship between the parameters and visual impressions of the modified textures were evaluated. This study shows that influence of both local and global structures of the texture along with their combinations and mutual interactions are important for identification of human visual impression.

  1. Imaging the Respiratory Effects of Opioids in the Human Brain.

    PubMed

    Pattinson, Kyle T S; Wise, Richard G

    2016-01-01

    Opioid analgesia is limited by the potentially fatal side effect of respiratory depression. In humans the brain mechanisms of opioid-induced respiratory depression are poorly understood. Investigating pharmacological influences upon breathing helps us to understand better the brain's respiratory control networks. Blood oxygen level-dependent (BOLD) functional magnetic resonance imaging (FMRI) maps neuronal activity in the brain, and is therefore a potentially useful, noninvasive technique to investigate the functional neuroanatomy of respiratory control in humans. Contrast in FMRI is derived from the vascular response to brain activity (neurovascular coupling). Therefore, FMRI studies of the neuronal effects of opioids are rendered more complex by the nonneuronal effects of opioids including those on systemic physiology, cerebral blood flow, and direct effects on the cerebral vasculature such as altered vascular reactivity. Here we review our series of studies that dissect the vascular and neuronal breathing-related effects of opioids in the brain. These methodological considerations have enabled successful FMRI studies revealing the brain networks responsible for opioid effects upon respiratory awareness. Similar considerations would be necessary for FMRI studies in hypoxia or in disease states that affect the physiological state of the brain. PMID:27343094

  2. Compact continuum brain model for human electroencephalogram

    NASA Astrophysics Data System (ADS)

    Kim, J. W.; Shin, H.-B.; Robinson, P. A.

    2007-12-01

    A low-dimensional, compact brain model has recently been developed based on physiologically based mean-field continuum formulation of electric activity of the brain. The essential feature of the new compact model is a second order time-delayed differential equation that has physiologically plausible terms, such as rapid corticocortical feedback and delayed feedback via extracortical pathways. Due to its compact form, the model facilitates insight into complex brain dynamics via standard linear and nonlinear techniques. The model successfully reproduces many features of previous models and experiments. For example, experimentally observed typical rhythms of electroencephalogram (EEG) signals are reproduced in a physiologically plausible parameter region. In the nonlinear regime, onsets of seizures, which often develop into limit cycles, are illustrated by modulating model parameters. It is also shown that a hysteresis can occur when the system has multiple attractors. As a further illustration of this approach, power spectra of the model are fitted to those of sleep EEGs of two subjects (one with apnea, the other with narcolepsy). The model parameters obtained from the fittings show good matches with previous literature. Our results suggest that the compact model can provide a theoretical basis for analyzing complex EEG signals.

  3. New insights into differences in brain organization between Neanderthals and anatomically modern humans

    PubMed Central

    Pearce, Eiluned; Stringer, Chris; Dunbar, R. I. M.

    2013-01-01

    Previous research has identified morphological differences between the brains of Neanderthals and anatomically modern humans (AMHs). However, studies using endocasts or the cranium itself are limited to investigating external surface features and the overall size and shape of the brain. A complementary approach uses comparative primate data to estimate the size of internal brain areas. Previous attempts to do this have generally assumed that identical total brain volumes imply identical internal organization. Here, we argue that, in the case of Neanderthals and AMHs, differences in the size of the body and visual system imply differences in organization between the same-sized brains of these two taxa. We show that Neanderthals had significantly larger visual systems than contemporary AMHs (indexed by orbital volume) and that when this, along with their greater body mass, is taken into account, Neanderthals have significantly smaller adjusted endocranial capacities than contemporary AMHs. We discuss possible implications of differing brain organization in terms of social cognition, and consider these in the context of differing abilities to cope with fluctuating resources and cultural maintenance. PMID:23486442

  4. Surface area and cortical thickness descriptors reveal different attributes of the structural human brain networks.

    PubMed

    Sanabria-Diaz, Gretel; Melie-García, Lester; Iturria-Medina, Yasser; Alemán-Gómez, Yasser; Hernández-González, Gertrudis; Valdés-Urrutia, Lourdes; Galán, Lídice; Valdés-Sosa, Pedro

    2010-05-01

    Recently, a related morphometry-based connection concept has been introduced using local mean cortical thickness and volume to study the underlying complex architecture of the brain networks. In this article, the surface area is employed as a morphometric descriptor to study the concurrent changes between brain structures and to build binarized connectivity graphs. The statistical similarity in surface area between pair of regions was measured by computing the partial correlation coefficient across 186 normal subjects of the Cuban Human Brain Mapping Project. We demonstrated that connectivity matrices obtained follow a small-world behavior for two different parcellations of the brain gray matter. The properties of the connectivity matrices were compared to the matrices obtained using the mean cortical thickness for the same cortical parcellations. The topology of the cortical thickness and surface area networks were statistically different, demonstrating that both capture distinct properties of the interaction or different aspects of the same interaction (mechanical, anatomical, chemical, etc.) between brain structures. This finding could be explained by the fact that each descriptor is driven by distinct cellular mechanisms as result of a distinct genetic origin. To our knowledge, this is the first time that surface area is used to study the morphological connectivity of brain networks. PMID:20083210

  5. A navigational guidance system in the human brain.

    PubMed

    Spiers, Hugo J; Maguire, Eleanor A

    2007-01-01

    Finding your way in large-scale space requires knowing where you currently are and how to get to your goal destination. While much is understood about the neural basis of one's current position during navigation, surprisingly little is known about how the human brain guides navigation to goals. Computational accounts argue that specific brain regions support navigational guidance by coding the proximity and direction to the goal, but empirical evidence for such mechanisms is lacking. Here, we scanned subjects with functional magnetic resonance imaging as they navigated to goal destinations in a highly accurate virtual simulation of a real city. Brain activity was then analyzed in combination with metric measures of proximity and direction to goal destinations that were derived from each individual subject's coordinates at every second of navigation. We found that activity in the medial prefrontal cortex was positively correlated, and activity in a right subicular/entorhinal region was negatively correlated with goal proximity. By contrast, activity in bilateral posterior parietal cortex was correlated with egocentric direction to goals. Our results provide empirical evidence for a navigational guidance system in the human brain, and define more precisely the contribution of these three brain regions to human navigation. In addition, these findings may also have wider implications for how the brain monitors and integrates different types of information in the service of goal-directed behavior in general. PMID:17492693

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

    NASA Astrophysics Data System (ADS)

    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.

  7. Distribution of vesicular glutamate transporters in the human brain

    PubMed Central

    Vigneault, Érika; Poirel, Odile; Riad, Mustapha; Prud'homme, Josée; Dumas, Sylvie; Turecki, Gustavo; Fasano, Caroline; Mechawar, Naguib; El Mestikawy, Salah

    2015-01-01

    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. PMID:25798091

  8. A navigational guidance system in the human brain

    PubMed Central

    Spiers, Hugo J.; Maguire, Eleanor A.

    2008-01-01

    Finding your way in large-scale space requires knowing where you currently are and how to get to your goal destination. While much is understood about the neural basis of one’s current position during navigation, surprisingly little is known about how the human brain guides navigation to goals. Computational accounts argue that specific brain regions support navigational guidance by coding the proximity and direction to the goal, but empirical evidence for such mechanisms is lacking. Here, we scanned subjects with functional MRI (fMRI) as they navigated to goal destinations in a highly accurate virtual simulation of a real city. Brain activity was then analysed in combination with metric measures of proximity and direction to goal destinations which were derived from each individual subject’s coordinates at every second of navigation. We found that activity in the medial prefrontal cortex was positively correlated, and activity in a right subicular/entorhinal region was negatively correlated with goal proximity. By contrast, activity in bilateral posterior parietal cortex was correlated with egocentric direction to goals. Our results provide empirical evidence for a navigational guidance system in the human brain, and define more precisely the contribution of these three brain regions to human navigation. In addition, these findings may also have wider implications for how the brain monitors and integrates different types of information in the service of goal-directed behaviour in general. PMID:17492693

  9. The brain and the braincase: a spatial analysis on the midsagittal profile in adult humans.

    PubMed

    Bruner, Emiliano; Amano, Hideki; de la Cuétara, José Manuel; Ogihara, Naomichi

    2015-09-01

    The spatial relationships between brain and braincase represent a major topic in surgery and evolutionary neuroanatomy. In paleoneurology, neurocranial landmarks are often used as references for brain areas. In this study, we analyze the variation and covariation of midsagittal brain and skull coordinates in a sample of adult modern humans in order to demonstrate spatial associations between hard and soft tissues. The correlation between parietal lobe size and parietal bone size is very low, and there is a marked individual variation. The distances between lobes and bones are partially influenced by the dimensions of the parietal lobes. The main pattern of morphological variability among individuals, associated with the size of the precuneus, apparently does not influence the position of the neurocranial sutures. Therefore, variations in precuneal size modify the distance between the paracentral lobule and bregma, and between the parietal lobe and lambda. Hence, the relative position of the cranial and cerebral landmarks can change as a function of the parietal dimensions. The slight correlation and covariation among these elements suggests a limited degree of spatial integration between soft and hard tissues. Therefore, although the brain influences the cranial size and shape during morphogenesis, the specific position of the cerebral components is sensitive to multiple effects and local factors, without a strict correspondence with the bone landmarks. This absence of correspondent change between brain and skull boundaries suggests caution when making inferences about the brain areas from the position of the cranial sutures. The fact that spatial relationships between cranial and brain areas may vary according to brain proportions must be considered in paleoneurology, when brain anatomy is inferred from cranial evidence. PMID:26200138

  10. Morphological structure and variations of lumbar plexus in human fetuses.

    PubMed

    Yasar, Soner; Kaya, Serdar; Temiz, Cağlar; Tehli, Ozkan; Kural, Cahit; Izci, Yusuf

    2014-04-01

    The objective of this study is to study the anatomy of lumbar plexus on human fetuses and to establish its morphometric characteristics and differences compared with adults. Twenty lumbar plexus of 10 human fetal cadavers in different gestational ages and genders were dissected. Lumbar spinal nerves, ganglions, and peripheral nerves were exposed. Normal anatomical structure and variations of lumbar plexus were investigated and morphometric analyses were performed. The diameters of lumbar spinal nerves increased from L1 to L4. The thickest nerve forming the plexus was femoral nerve, the thinnest was ilioinguinal nerve, the longest nerve through posterior abdominal wall was iliohypogastric nerve, and the shortest nerve was femoral nerve. Each plexus had a single furcal nerve and this arose from L4 nerve in all fetuses. No prefix or postfix plexus variation was observed. In two plexuses, L1 nerve was in the form of a single branch. Also, in two plexuses, genitofemoral nerve arose only from L2 nerve. Accessory obturator nerve was observed in four plexuses. According to these findings, the morphological pattern of the lumbar plexus in the fetus was found to be very similar to the lumbar plexus in adults. PMID:22696243

  11. Decoding the visual and subjective contents of the human brain.

    PubMed

    Kamitani, Yukiyasu; Tong, Frank

    2005-05-01

    The potential for human neuroimaging to read out the detailed contents of a person's mental state has yet to be fully explored. We investigated whether the perception of edge orientation, a fundamental visual feature, can be decoded from human brain activity measured with functional magnetic resonance imaging (fMRI). Using statistical algorithms to classify brain states, we found that ensemble fMRI signals in early visual areas could reliably predict on individual trials which of eight stimulus orientations the subject was seeing. Moreover, when subjects had to attend to one of two overlapping orthogonal gratings, feature-based attention strongly biased ensemble activity toward the attended orientation. These results demonstrate that fMRI activity patterns in early visual areas, including primary visual cortex (V1), contain detailed orientation information that can reliably predict subjective perception. Our approach provides a framework for the readout of fine-tuned representations in the human brain and their subjective contents. PMID:15852014

  12. Individual differences in anthropomorphic attributions and human brain structure

    PubMed Central

    Kanai, Ryota; Bahrami, Bahador; Rees, Geraint

    2014-01-01

    Anthropomorphism is the attribution of human characteristics or behaviour to animals, non-living things or natural phenomena. It is pervasive among humans, yet nonetheless exhibits a high degree of inter-individual variability. We hypothesized that brain areas associated with anthropomorphic thinking might be similar to those engaged in the attribution of mental states to other humans, the so-called ‘theory of mind’ or mentalizing network. To test this hypothesis, we related brain structure measured using magnetic resonance imaging in a sample of 83 healthy young adults to a simple, self-report questionnaire that measured the extent to which our participants made anthropomorphic attributions about non-human animals and non-animal stimuli. We found that individual differences in anthropomorphism for non-human animals correlated with the grey matter volume of the left temporoparietal junction, a brain area involved in mentalizing. Our data support previous work indicating a link between areas of the brain involved in attributing mental states to other humans and those involved in anthropomorphism. PMID:23887807

  13. Tracking neuronal fiber pathways in the living human brain

    PubMed Central

    Conturo, Thomas E.; Lori, Nicolas F.; Cull, Thomas S.; Akbudak, Erbil; Snyder, Abraham Z.; Shimony, Joshua S.; McKinstry, Robert C.; Burton, Harold; Raichle, Marcus E.

    1999-01-01

    Functional imaging with positron emission tomography and functional MRI has revolutionized studies of the human brain. Understanding the organization of brain systems, especially those used for cognition, remains limited, however, because no methods currently exist for noninvasive tracking of neuronal connections between functional regions [Crick, F. & Jones, E. (1993) Nature (London) 361, 109–110]. Detailed connectivities have been studied in animals through invasive tracer techniques, but these invasive studies cannot be done in humans, and animal results cannot always be extrapolated to human systems. We have developed noninvasive neuronal fiber tracking for use in living humans, utilizing the unique ability of MRI to characterize water diffusion. We reconstructed fiber trajectories throughout the brain by tracking the direction of fastest diffusion (the fiber direction) from a grid of seed points, and then selected tracks that join anatomically or functionally (functional MRI) defined regions. We demonstrate diffusion tracking of fiber bundles in a variety of white matter classes with examples in the corpus callosum, geniculo-calcarine, and subcortical association pathways. Tracks covered long distances, navigated through divergences and tight curves, and manifested topological separations in the geniculo-calcarine tract consistent with tracer studies in animals and retinotopy studies in humans. Additionally, previously undescribed topologies were revealed in the other pathways. This approach enhances the power of modern imaging by enabling study of fiber connections among anatomically and functionally defined brain regions in individual human subjects. PMID:10468624

  14. Elevated gene expression levels distinguish human from non-human primate brains

    PubMed Central

    Cáceres, Mario; Lachuer, Joel; Zapala, Matthew A.; Redmond, John C.; Kudo, Lili; Geschwind, Daniel H.; Lockhart, David J.; Preuss, Todd M.; Barlow, Carrolee

    2003-01-01

    Little is known about how the human brain differs from that of our closest relatives. To investigate the genetic basis of human specializations in brain organization and cognition, we compared gene expression profiles for the cerebral cortex of humans, chimpanzees, and rhesus macaques by using several independent techniques. We identified 169 genes that exhibited expression differences between human and chimpanzee cortex, and 91 were ascribed to the human lineage by using macaques as an outgroup. Surprisingly, most differences between the brains of humans and non-human primates involved up-regulation, with ≈90% of the genes being more highly expressed in humans. By contrast, in the comparison of human and chimpanzee heart and liver, the numbers of up- and down-regulated genes were nearly identical. Our results indicate that the human brain displays a distinctive pattern of gene expression relative to non-human primates, with higher expression levels for many genes belonging to a wide variety of functional classes. The increased expression of these genes could provide the basis for extensive modifications of cerebral physiology and function in humans and suggests that the human brain is characterized by elevated levels of neuronal activity. PMID:14557539

  15. Telomerase Activity is Downregulated Early During Human Brain Development

    PubMed Central

    Ishaq, Abbas; Hanson, Peter S.; Morris, Christopher M.; Saretzki, Gabriele

    2016-01-01

    Changes in hTERT splice variant expression have been proposed to facilitate the decrease of telomerase activity during fetal development in various human tissues. Here, we analyzed the expression of telomerase RNA (hTR), wild type and α-spliced hTERT in developing human fetal brain (post conception weeks, pcw, 6–19) and in young and old cortices using qPCR and correlated it to telomerase activity measured by TRAP assay. Decrease of telomerase activity occurred early during brain development and correlated strongest to decreased hTR expression. The expression of α-spliced hTERT increased between pcw 10 and 19, while that of wild type hTERT remained unchanged. Lack of expression differences between young and old cortices suggests that most changes seem to occur early during human brain development. Using in vitro differentiation of neural precursor stem cells (NPSCs) derived at pcw 6 we found a decrease in telomerase activity but no major expression changes in telomerase associated genes. Thus, they do not seem to model the mechanisms for the decrease in telomerase activity in fetal brains. Our results suggest that decreased hTR levels, as well as transient increase in α-spliced hTERT, might both contribute to downregulation of telomerase activity during early human brain development between 6 and 17 pcw. PMID:27322326

  16. Expansion of Multipotent Stem Cells from the Adult Human Brain

    PubMed Central

    Murrell, Wayne; Palmero, Emily; Bianco, John; Stangeland, Biljana; Joel, Mrinal; Paulson, Linda; Thiede, Bernd; Grieg, Zanina; Ramsnes, Ingunn; Skjellegrind, Håvard K.; Nygård, Ståle; Brandal, Petter; Sandberg, Cecilie; Vik-Mo, Einar; Palmero, Sheryl; Langmoen, Iver A.

    2013-01-01

    The discovery of stem cells in the adult human brain has revealed new possible scenarios for treatment of the sick or injured brain. Both clinical use of and preclinical research on human adult neural stem cells have, however, been seriously hampered by the fact that it has been impossible to passage these cells more than a very few times and with little expansion of cell numbers. Having explored a number of alternative culturing conditions we here present an efficient method for the establishment and propagation of human brain stem cells from whatever brain tissue samples we have tried. We describe virtually unlimited expansion of an authentic stem cell phenotype. Pluripotency proteins Sox2 and Oct4 are expressed without artificial induction. For the first time multipotency of adult human brain-derived stem cells is demonstrated beyond tissue boundaries. We characterize these cells in detail in vitro including microarray and proteomic approaches. Whilst clarification of these cells’ behavior is ongoing, results so far portend well for the future repair of tissues by transplantation of an adult patient’s own-derived stem cells. PMID:23967194

  17. Telomerase Activity is Downregulated Early During Human Brain Development.

    PubMed

    Ishaq, Abbas; Hanson, Peter S; Morris, Christopher M; Saretzki, Gabriele

    2016-01-01

    Changes in hTERT splice variant expression have been proposed to facilitate the decrease of telomerase activity during fetal development in various human tissues. Here, we analyzed the expression of telomerase RNA (hTR), wild type and α-spliced hTERT in developing human fetal brain (post conception weeks, pcw, 6-19) and in young and old cortices using qPCR and correlated it to telomerase activity measured by TRAP assay. Decrease of telomerase activity occurred early during brain development and correlated strongest to decreased hTR expression. The expression of α-spliced hTERT increased between pcw 10 and 19, while that of wild type hTERT remained unchanged. Lack of expression differences between young and old cortices suggests that most changes seem to occur early during human brain development. Using in vitro differentiation of neural precursor stem cells (NPSCs) derived at pcw 6 we found a decrease in telomerase activity but no major expression changes in telomerase associated genes. Thus, they do not seem to model the mechanisms for the decrease in telomerase activity in fetal brains. Our results suggest that decreased hTR levels, as well as transient increase in α-spliced hTERT, might both contribute to downregulation of telomerase activity during early human brain development between 6 and 17 pcw. PMID:27322326

  18. Glucose transporter of the human brain and blood-brain barrier

    SciTech Connect

    Kalaria, R.N.; Gravina, S.A.; Schmidley, J.W.; Perry, G.; Harik, S.I.

    1988-12-01

    We identified and characterized the glucose transporter in the human cerebral cortex, cerebral microvessels, and choroid plexus by specific D-glucose-displaceable (3H)cytochalasin B binding. The binding was saturable, with a dissociation constant less than 1 microM. Maximal binding capacity was approximately 7 pmol/mg protein in the cerebral cortex, approximately 42 pmol/mg protein in brain microvessels, and approximately 27 pmol/mg protein in the choroid plexus. Several hexoses displaced specific (3H)cytochalasin B binding to microvessels in a rank-order that correlated well with their known ability to cross the blood-brain barrier; the only exception was 2-deoxy-D-glucose, which had much higher affinity for the glucose transporter than the natural substrate, D-glucose. Irreversible photoaffinity labeling of the glucose transporter of microvessels with (3H)cytochalasin B, followed by solubilization and polyacrylamide gel electrophoresis, labeled a protein band with an average molecular weight of approximately 55,000. Monoclonal and polyclonal antibodies specific to the human erythrocyte glucose transporter immunocytochemically stained brain blood vessels and the few trapped erythrocytes in situ, with minimal staining of the neuropil. In the choroid plexus, blood vessels did not stain, but the epithelium reacted positively. We conclude that human brain microvessels are richly endowed with a glucose transport moiety similar in molecular weight and antigenic characteristics to that of human erythrocytes and brain microvessels of other mammalian species.

  19. Measuring dopamine release in the human brain with PET

    SciTech Connect

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

    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.

  20. Morphology of nerve endings in vocal fold of human newborn.

    PubMed

    Gonçalves da Silva Leite, Janaina; Costa Cavalcante, Maria Luzete; Fechine-Jamacaru, Francisco Vagnaldo; de Lima Pompeu, Margarida Maria; Leite, José Alberto Dias; Nascimento Coelho, Dulce Maria; Rabelo de Freitas, Marcos

    2016-10-01

    Sensory receptors are distributed throughout the oral cavity, pharynx, and larynx. Laryngeal sensitivity is crucial for maintaining safe swallowing, thus avoiding silent aspiration. Morphologic description of different receptor types present in larynx vary because of the study of many different species, from mouse to humans. The most commonly sensory structures described in laryngeal mucosa are free nerve endings, taste buds, muscle spindles, glomerular and corpuscular receptors. This study aimed at describing the morphology and the distribution of nerve endings in premature newborn glottic region. Transversal serial frozen sections of the whole vocal folds of three newborns were analyzed using an immuno-histochemical process with a pan-neuronal marker anti-protein gene product 9.5 (PGP 9.5). Imaging was done using a confocal laser microscope. Nerve fiber density in vocal cord was calculated using panoramic images in software Morphometric Analysis System v1.0. Some sensory structures, i.e. glomerular endings and intraepithelial free nerve endings were found in the vocal cord mucosa. Muscle spindles, complex nerve endings (Meissner-like, spherical, rectangular and growing) spiral-wharves nerve structures were identified in larynx intrinsic muscles. Nervous total mean density in vocal cord was similar in the three newborns, although they had different gestational age. The mean nerve fiber density was higher in the posterior region than anterior region of vocal cord. The present results demonstrate the occurrence of different morphotypes of sensory corpuscles and nerve endings premature newborn glottic region and provide information on their sensory systems. PMID:27619029

  1. Staphylococcus massiliensis sp. nov., isolated from a human brain abscess.

    PubMed

    Al Masalma, Mouhamad; Raoult, Didier; Roux, Véronique

    2010-05-01

    Gram-positive, catalase-positive, coagulase-negative, non-motile, non-fermentative and novobiocin-susceptible cocci were isolated from a human brain abscess sample (strain 5402776(T)). This novel strain was analysed by a polyphasic taxonomic approach. The respiratory quinones detected were MK-7 (93 %) and MK-6 (7 %) and the major fatty acids were C(15 : 0) iso (60.5 %), C(17 : 0) iso (8.96 %) C(15 : 0) anteiso (7.93 %) and C(19 : 0) iso (6.78 %). The peptidoglycan type was A3alpha l-Lys-Gly(2-3)-l-Ser-Gly. Based on cellular morphology and biochemical criteria, the new isolate was assigned to the genus Staphylococcus, although it did not correspond to any recognized species. The G+C content of the DNA was 36.6 mol%. Phylogenetic analysis based on 16S rRNA gene sequence comparisons showed that the new isolate was most closely related to Staphylococcus piscifermentans, Staphylococcus condimenti, Staphylococcus carnosus subsp. carnosus, S. carnosus subsp. utilis and Staphylococcus simulans (97.7 %, 97.6 %, 97.6 %, 97.6 % and 96.5 % sequence similarity, respectively). Comparison of tuf, hsp60, rpoB, dnaJ and sodA gene sequences was also performed. In phylogenetic analysis inferred from tuf, dnaJ and rpoB gene sequence comparisons, strain 5402776(T) clustered with Staphylococcus pettenkoferi (93.7 %, 82.5 % and 89 % sequence similarity, respectively) and on phylogenetic analysis inferred from sodA gene sequence comparisons, it clustered with Staphylococcus chromogenes (82.8 %). On the basis of phenotypic and genotypic data, this isolate represents a novel species for which the name Staphylococcus massiliensis sp. nov. is proposed (type strain 5402776(T)=CCUG 55927(T)=CSUR P23(T)). PMID:19666814

  2. Simplified detection system for neuroreceptor studies in the human brain

    SciTech Connect

    Bice, A.N.; Wagner, H.N. Jr.; Frost, J.J.; Natarajan, T.K.; Lee, M.C.; Wong, D.F.; Dannals, R.F.; Ravert, H.T.; Wilson, A.A.; Links, J.M.

    1986-02-01

    A simple, inexpensive dual-detector system has been developed for measurement of positronemitting receptor-binding drugs in the human brain. This high efficiency coincidence counting system requires that only a few hundred microcuries of labeled drug be administered to the subject, thereby allowing for multiple studies without an excessive radiation dose. Measurement of the binding of (11C)carfentanil, a high affinity synthetic opiate, to opiate receptors in the presence and in the absence of a competitive opiate antagonist indicates the potential utility of this system for estimating different degrees of receptor occupation in the human brain.

  3. Optical dosimetry in photodynamic therapy of human uterus and brain

    NASA Astrophysics Data System (ADS)

    Madsen, Steen J.; Svaasand, Lars O.; Hirschberg, Henry; Tadir, Yona; Tromberg, Bruce J.

    1999-06-01

    Optical 'dose' is one of the fundamental parameters required in the design of an efficacious regimen of photodynamic therapy (PDT). The issues involved in delivering a sufficient optical dose to the human uterus and brain during PDT will be discussed. Specifically, measurements of optical properties and fluence rates in excised human uteri are presented. Measured fluence rates are compared to the predictions of a simple diffusion model and the clinical utility of the treatment is discussed. The delivery of light to brain tissue via a surgically implanted balloon applicator will also be considered. The time required to deliver and adequate dose is calculated based on known optical properties and diffusion theory.

  4. Mu opioid receptor binding sites in human brain

    SciTech Connect

    Pilapil, C.; Welner, S.; Magnan, J.; Zamir, N.; Quirion, R.

    1986-01-01

    Our experiments focused on the examination of the distribution of mu opioid receptor binding sites in normal human brain using the highly selective ligand (/sup 3/H)DAGO, in both membrane binding assay and in vitro receptor autoradiography. Mu opioid binding sites are very discretely distributed in human brain with high densities of sites found in the posterior amygdala, caudate, putamen, hypothalamus and certain cortical areas. Moreover the autoradiographic distribution of (/sup 3/H)DAGO binding sites clearly reveals the discrete lamination (layers I and III-IV) of mu sites in cortical areas.

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

    SciTech Connect

    Volkow, N.D.; Fowler, J.S.; Gatley, S. |

    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.

  6. Human brain spots emotion in non humanoid robots

    PubMed Central

    Foucher, Aurélie; Jouvent, Roland; Nadel, Jacqueline

    2011-01-01

    The computation by which our brain elaborates fast responses to emotional expressions is currently an active field of brain studies. Previous studies have focused on stimuli taken from everyday life. Here, we investigated event-related potentials in response to happy vs neutral stimuli of human and non-humanoid robots. At the behavioural level, emotion shortened reaction times similarly for robotic and human stimuli. Early P1 wave was enhanced in response to happy compared to neutral expressions for robotic as well as for human stimuli, suggesting that emotion from robots is encoded as early as human emotion expression. Congruent with their lower faceness properties compared to human stimuli, robots elicited a later and lower N170 component than human stimuli. These findings challenge the claim that robots need to present an anthropomorphic aspect to interact with humans. Taken together, such results suggest that the early brain processing of emotional expressions is not bounded to human-like arrangements embodying emotion. PMID:20194513

  7. Human brain spots emotion in non humanoid robots.

    PubMed

    Dubal, Stéphanie; Foucher, Aurélie; Jouvent, Roland; Nadel, Jacqueline

    2011-01-01

    The computation by which our brain elaborates fast responses to emotional expressions is currently an active field of brain studies. Previous studies have focused on stimuli taken from everyday life. Here, we investigated event-related potentials in response to happy vs neutral stimuli of human and non-humanoid robots. At the behavioural level, emotion shortened reaction times similarly for robotic and human stimuli. Early P1 wave was enhanced in response to happy compared to neutral expressions for robotic as well as for human stimuli, suggesting that emotion from robots is encoded as early as human emotion expression. Congruent with their lower faceness properties compared to human stimuli, robots elicited a later and lower N170 component than human stimuli. These findings challenge the claim that robots need to present an anthropomorphic aspect to interact with humans. Taken together, such results suggest that the early brain processing of emotional expressions is not bounded to human-like arrangements embodying emotion. PMID:20194513

  8. Abnormal Subcortical Brain Morphology in Patients with Knee Osteoarthritis: A Cross-sectional Study

    PubMed Central

    Mao, Cui Ping; Bai, Zhi Lan; Zhang, Xiao Na; Zhang, Qiu Juan; Zhang, Lei

    2016-01-01

    Despite the involvement of subcortical brain structures in the pathogenesis of chronic pain and persistent pain as the defining symptom of knee osteoarthritis (KOA), little attention has been paid to the morphometric measurements of these subcortical nuclei in patients with KOA. The purpose of this study is to explore the potential morphological abnormalities of subcortical brain structures in patients with KOA as compared to the healthy control subjects by using high-resolution MRI. Structural MR data were acquired from 26 patients with KOA and 31 demographically similar healthy individuals. The MR data were analyzed by using FMRIB’s integrated registration and segmentation tool. Both volumetric analysis and surface-based shape analysis were performed to characterize the subcortical morphology. The normalized volumes of bilateral caudate nucleus were significantly smaller in the KOA group than in the control group (P = 0.004). There was also a trend toward smaller volume of the hippocampus in KOA as compared to the control group (P = 0.027). Detailed surface analyses further localized these differences with a greater involvement of the left hemisphere (P < 0.05, corrected) for the caudate nucleus. Hemispheric asymmetry (right larger than left) of the caudate nucleus was found in both KOA and control groups. Besides, no significant correlation was found between the structural data and pain intensities. Our results indicated that patients with KOA had statistically significant smaller normalized volumes of bilateral caudate nucleus and a trend toward smaller volume of the hippocampus as compared to the control subjects. Further investigations are necessary to characterize the role of caudate nucleus in the course of chronicity of pain associated with KOA. PMID:26834629

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

    PubMed

    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. PMID:23256049

  10. Common genetic variants influence human subcortical brain structures.

    PubMed

    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

    2015-04-01

    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 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 volume and intracranial volume. 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 in human brain development, and may help to determine mechanisms of neuropsychiatric dysfunction. PMID:25607358