WorldWideScience

Sample records for model human brain

  1. Computational Intelligence in a Human Brain Model

    Directory of Open Access Journals (Sweden)

    Viorel Gaftea

    2016-06-01

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

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

    Science.gov (United States)

    Han, Shihui; Ma, Yina

    2015-11-01

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

  3. Multilayer modeling and analysis of human brain networks.

    Science.gov (United States)

    De Domenico, Manlio

    2017-05-01

    Understanding how the human brain is structured, and how its architecture is related to function, is of paramount importance for a variety of applications, including but not limited to new ways to prevent, deal with, and cure brain diseases, such as Alzheimer's or Parkinson's, and psychiatric disorders, such as schizophrenia. The recent advances in structural and functional neuroimaging, together with the increasing attitude toward interdisciplinary approaches involving computer science, mathematics, and physics, are fostering interesting results from computational neuroscience that are quite often based on the analysis of complex network representation of the human brain. In recent years, this representation experienced a theoretical and computational revolution that is breaching neuroscience, allowing us to cope with the increasing complexity of the human brain across multiple scales and in multiple dimensions and to model structural and functional connectivity from new perspectives, often combined with each other. In this work, we will review the main achievements obtained from interdisciplinary research based on magnetic resonance imaging and establish de facto, the birth of multilayer network analysis and modeling of the human brain. © The Author 2017. Published by Oxford University Press.

  4. A hierarchical model of the evolution of human brain specializations

    Science.gov (United States)

    Barrett, H. Clark

    2012-01-01

    The study of information-processing adaptations in the brain is controversial, in part because of disputes about the form such adaptations might take. Many psychologists assume that adaptations come in two kinds, specialized and general-purpose. Specialized mechanisms are typically thought of as innate, domain-specific, and isolated from other brain systems, whereas generalized mechanisms are developmentally plastic, domain-general, and interactive. However, if brain mechanisms evolve through processes of descent with modification, they are likely to be heterogeneous, rather than coming in just two kinds. They are likely to be hierarchically organized, with some design features widely shared across brain systems and others specific to particular processes. Also, they are likely to be largely developmentally plastic and interactive with other brain systems, rather than canalized and isolated. This article presents a hierarchical model of brain specialization, reviewing evidence for the model from evolutionary developmental biology, genetics, brain mapping, and comparative studies. Implications for the search for uniquely human traits are discussed, along with ways in which conventional views of modularity in psychology may need to be revised. PMID:22723350

  5. Rotenone exerts developmental neurotoxicity in a human brain spheroid model.

    Science.gov (United States)

    Pamies, David; Block, Katharina; Lau, Pierre; Gribaldo, Laura; Pardo, Carlos A; Barreras, Paula; Smirnova, Lena; Wiersma, Daphne; Zhao, Liang; Harris, Georgina; Hartung, Thomas; Hogberg, Helena T

    2018-02-08

    Growing concern suggests that some chemicals exert (developmental) neurotoxicity (DNT and NT) and are linked to the increase in incidence of autism, attention deficit and hyperactivity disorders. The high cost of routine tests for DNT and NT assessment make it difficult to test the high numbers of existing chemicals. Thus, more cost effective neurodevelopmental models are needed. The use of induced pluripotent stem cells (iPSC) in combination with the emerging human 3D tissue culture platforms, present a novel tool to predict and study human toxicity. By combining these technologies, we generated multicellular brain spheroids (BrainSpheres) from human iPSC. The model has previously shown to be reproducible and recapitulates several neurodevelopmental features. Our results indicate, rotenone's toxic potency varies depending on the differentiation status of the cells, showing higher reactive oxygen species (ROS) and higher mitochondrial dysfunction during early than later differentiation stages. Immuno-fluorescence morphology analysis after rotenone exposure indicated dopaminergic-neuron selective toxicity at non-cytotoxic concentrations (1 μM), while astrocytes and other neuronal cell types were affected at (general) cytotoxic concentrations (25 μM). Omics analysis showed changes in key pathways necessary for brain development, indicating rotenone as a developmental neurotoxicant and show a possible link between previously shown effects on neurite outgrowth and presently observed effects on Ca2+ reabsorption, synaptogenesis and PPAR pathway disruption. In conclusion, our BrainSpheres model has shown to be a reproducible and novel tool to study neurotoxicity and developmental neurotoxicity. Results presented here support the idea that rotenone can potentially be a developmental neurotoxicant. Copyright © 2018. Published by Elsevier Inc.

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

    Science.gov (United States)

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

    2017-06-01

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

  7. A reproducible brain tumour model established from human glioblastoma biopsies

    Directory of Open Access Journals (Sweden)

    Li Xingang

    2009-12-01

    Full Text Available Abstract Background Establishing clinically relevant animal models of glioblastoma multiforme (GBM remains a challenge, and many commonly used cell line-based models do not recapitulate the invasive growth patterns of patient GBMs. Previously, we have reported the formation of highly invasive tumour xenografts in nude rats from human GBMs. However, implementing tumour models based on primary tissue requires that these models can be sufficiently standardised with consistently high take rates. Methods In this work, we collected data on growth kinetics from a material of 29 biopsies xenografted in nude rats, and characterised this model with an emphasis on neuropathological and radiological features. Results The tumour take rate for xenografted GBM biopsies were 96% and remained close to 100% at subsequent passages in vivo, whereas only one of four lower grade tumours engrafted. Average time from transplantation to the onset of symptoms was 125 days ± 11.5 SEM. Histologically, the primary xenografts recapitulated the invasive features of the parent tumours while endothelial cell proliferations and necrosis were mostly absent. After 4-5 in vivo passages, the tumours became more vascular with necrotic areas, but also appeared more circumscribed. MRI typically revealed changes related to tumour growth, several months prior to the onset of symptoms. Conclusions In vivo passaging of patient GBM biopsies produced tumours representative of the patient tumours, with high take rates and a reproducible disease course. The model provides combinations of angiogenic and invasive phenotypes and represents a good alternative to in vitro propagated cell lines for dissecting mechanisms of brain tumour progression.

  8. Local Model of Arteriovenous Malformation of the Human Brain

    International Nuclear Information System (INIS)

    Telegina, Nadezhda; Chupakhin, Aleksandr; Cherevko, Aleksandr

    2013-01-01

    Vascular diseases of the human brain are one of the reasons of deaths and people's incapacitation not only in Russia, but also in the world. The danger of an arteriovenous malformation (AVM) is in premature rupture of pathological vessels of an AVM which may cause haemorrhage. Long-term prognosis without surgical treatment is unfavorable. The reduced impact method of AVM treatment is embolization of a malformation which often results in complete obliteration of an AVM. Pre-surgical mathematical modeling of an arteriovenous malformation can help surgeons with an optimal sequence of the operation. During investigations, the simple mathematical model of arteriovenous malformation is developed and calculated, and stationary and non-stationary processes of its embolization are considered. Various sequences of embolization of a malformation are also considered. Calculations were done with approximate steady flow on the basis of balanced equations derived from conservation laws. Depending on pressure difference, a fistula-type AVM should be embolized at first, and then small racemose AVMs are embolized. Obtained results are in good correspondence with neurosurgical AVM practice.

  9. Non-human Primate Models for Brain Disorders - Towards Genetic Manipulations via Innovative Technology.

    Science.gov (United States)

    Qiu, Zilong; Li, Xiao

    2017-04-01

    Modeling brain disorders has always been one of the key tasks in neurobiological studies. A wide range of organisms including worms, fruit flies, zebrafish, and rodents have been used for modeling brain disorders. However, whether complicated neurological and psychiatric symptoms can be faithfully mimicked in animals is still debatable. In this review, we discuss key findings using non-human primates to address the neural mechanisms underlying stress and anxiety behaviors, as well as technical advances for establishing genetically-engineered non-human primate models of autism spectrum disorders and other disorders. Considering the close evolutionary connections and similarity of brain structures between non-human primates and humans, together with the rapid progress in genome-editing technology, non-human primates will be indispensable for pathophysiological studies and exploring potential therapeutic methods for treating brain disorders.

  10. A Comparative Study of Theoretical Graph Models for Characterizing Structural Networks of Human Brain

    Directory of Open Access Journals (Sweden)

    Xiaojin Li

    2013-01-01

    Full Text Available Previous studies have investigated both structural and functional brain networks via graph-theoretical methods. However, there is an important issue that has not been adequately discussed before: what is the optimal theoretical graph model for describing the structural networks of human brain? In this paper, we perform a comparative study to address this problem. Firstly, large-scale cortical regions of interest (ROIs are localized by recently developed and validated brain reference system named Dense Individualized Common Connectivity-based Cortical Landmarks (DICCCOL to address the limitations in the identification of the brain network ROIs in previous studies. Then, we construct structural brain networks based on diffusion tensor imaging (DTI data. Afterwards, the global and local graph properties of the constructed structural brain networks are measured using the state-of-the-art graph analysis algorithms and tools and are further compared with seven popular theoretical graph models. In addition, we compare the topological properties between two graph models, namely, stickiness-index-based model (STICKY and scale-free gene duplication model (SF-GD, that have higher similarity with the real structural brain networks in terms of global and local graph properties. Our experimental results suggest that among the seven theoretical graph models compared in this study, STICKY and SF-GD models have better performances in characterizing the structural human brain network.

  11. A physical multifield model predicts the development of volume and structure in the human brain

    Science.gov (United States)

    Rooij, Rijk de; Kuhl, Ellen

    2018-03-01

    The prenatal development of the human brain is characterized by a rapid increase in brain volume and a development of a highly folded cortex. At the cellular level, these events are enabled by symmetric and asymmetric cell division in the ventricular regions of the brain followed by an outwards cell migration towards the peripheral regions. The role of mechanics during brain development has been suggested and acknowledged in past decades, but remains insufficiently understood. Here we propose a mechanistic model that couples cell division, cell migration, and brain volume growth to accurately model the developing brain between weeks 10 and 29 of gestation. Our model accurately predicts a 160-fold volume increase from 1.5 cm3 at week 10 to 235 cm3 at week 29 of gestation. In agreement with human brain development, the cortex begins to form around week 22 and accounts for about 30% of the total brain volume at week 29. Our results show that cell division and coupling between cell density and volume growth are essential to accurately model brain volume development, whereas cell migration and diffusion contribute mainly to the development of the cortex. We demonstrate that complex folding patterns, including sinusoidal folds and creases, emerge naturally as the cortex develops, even for low stiffness contrasts between the cortex and subcortex.

  12. Validation of In Vitro Cell-Based Human Blood-Brain Barrier Model Using Clinical Positron Emission Tomography Radioligands To Predict In Vivo Human Brain Penetration

    International Nuclear Information System (INIS)

    Mabondzo, A.; Guyot, A.C.; Bottlaender, M.; Deverre, J.R.; Tsaouin, K.; Balimane, P.V.

    2010-01-01

    We have evaluated a novel in vitro cell-based human blood-brain barrier (BBB) model that could predict in vivo human brain penetration for compounds with different BBB permeabilities using the clinical positron emission tomography (PET) data. Comparison studies were also performed to demonstrate that the in vitro cell-based human BBB model resulted in better predictivity over the traditional permeability model in discovery organizations, Caco-2 cells. We evaluated the in vivo BBB permeability of [ 18 F] and [ 11 C]-compounds in humans by PET imaging. The in vivo plasma-brain exchange parameters used for comparison were determined in humans by PET using a kinetic analysis of the radiotracer binding. For each radiotracer, the parameters were determined by fitting the brain kinetics of the radiotracer using a two-tissue compartment model of the ligand-receptor interaction. Bidirectional transport studies with the same compounds as in in vivo studies were carried out using the in vitro cell-based human BBB model as well as Caco-2 cells. The in vitro cell-based human BBB model has important features of the BBB in vivo and is suitable for discriminating between CNS and non-CNS marketed drugs. A very good correlation (r 2 =0.90; P≤0.001) was demonstrated between in vitro BBB permeability and in vivo permeability coefficient. In contrast, a poor correlation (r 2 = 0.17) was obtained between Caco-2 data and in vivo human brain penetration. This study highlights the potential of this in vitro cell-based human BBB model in drug discovery and shows that it can be an extremely effective screening tool for CNS programs. (authors)

  13. Empirical Network Model of Human Higher Cognitive Brain Functions

    Science.gov (United States)

    1990-03-31

    inference of the cogni- tive psychologists, psychophysiologists, neu- tive processes tairing placa during brief analy- rologists and psychiatrists that so...John and Schwartz 1978) that result from direct communication between cortical distinguish between early exogenous and later en- 0 EVENT-RELATED...Bartlett. F.. Thatcher. R.. Kaye. H.. Valdes. P and Schwartz . E. i 1977a) Neurometmcs: numencal taxonomy identifies different profiles of brain functions

  14. A stable and reproducible human blood-brain barrier model derived from hematopoietic stem cells.

    Directory of Open Access Journals (Sweden)

    Romeo Cecchelli

    Full Text Available The human blood brain barrier (BBB is a selective barrier formed by human brain endothelial cells (hBECs, which is important to ensure adequate neuronal function and protect the central nervous system (CNS from disease. The development of human in vitro BBB models is thus of utmost importance for drug discovery programs related to CNS diseases. Here, we describe a method to generate a human BBB model using cord blood-derived hematopoietic stem cells. The cells were initially differentiated into ECs followed by the induction of BBB properties by co-culture with pericytes. The brain-like endothelial cells (BLECs express tight junctions and transporters typically observed in brain endothelium and maintain expression of most in vivo BBB properties for at least 20 days. The model is very reproducible since it can be generated from stem cells isolated from different donors and in different laboratories, and could be used to predict CNS distribution of compounds in human. Finally, we provide evidence that Wnt/β-catenin signaling pathway mediates in part the BBB inductive properties of pericytes.

  15. Computational modeling of blast wave interaction with a human body and assessment of traumatic brain injury

    Science.gov (United States)

    Tan, X. G.; Przekwas, A. J.; Gupta, R. K.

    2017-11-01

    The modeling of human body biomechanics resulting from blast exposure poses great challenges because of the complex geometry and the substantial material heterogeneity. We developed a detailed human body finite element model representing both the geometry and the materials realistically. The model includes the detailed head (face, skull, brain and spinal cord), the neck, the skeleton, air cavities (lungs) and the tissues. Hence, it can be used to properly model the stress wave propagation in the human body subjected to blast loading. The blast loading on the human was generated from a simulated C4 explosion. We used the highly scalable solvers in the multi-physics code CoBi for both the blast simulation and the human body biomechanics. The meshes generated for these simulations are of good quality so that relatively large time-step sizes can be used without resorting to artificial time scaling treatments. The coupled gas dynamics and biomechanics solutions were validated against the shock tube test data. The human body models were used to conduct parametric simulations to find the biomechanical response and the brain injury mechanism due to blasts impacting the human body. Under the same blast loading condition, we showed the importance of inclusion of the whole body.

  16. A geometric network model of intrinsic grey-matter connectivity of the human brain

    Science.gov (United States)

    Lo, Yi-Ping; O'Dea, Reuben; Crofts, Jonathan J.; Han, Cheol E.; Kaiser, Marcus

    2015-10-01

    Network science provides a general framework for analysing the large-scale brain networks that naturally arise from modern neuroimaging studies, and a key goal in theoretical neuroscience is to understand the extent to which these neural architectures influence the dynamical processes they sustain. To date, brain network modelling has largely been conducted at the macroscale level (i.e. white-matter tracts), despite growing evidence of the role that local grey matter architecture plays in a variety of brain disorders. Here, we present a new model of intrinsic grey matter connectivity of the human connectome. Importantly, the new model incorporates detailed information on cortical geometry to construct ‘shortcuts’ through the thickness of the cortex, thus enabling spatially distant brain regions, as measured along the cortical surface, to communicate. Our study indicates that structures based on human brain surface information differ significantly, both in terms of their topological network characteristics and activity propagation properties, when compared against a variety of alternative geometries and generative algorithms. In particular, this might help explain histological patterns of grey matter connectivity, highlighting that observed connection distances may have arisen to maximise information processing ability, and that such gains are consistent with (and enhanced by) the presence of short-cut connections.

  17. Mathematical modeling of human glioma growth based on brain topological structures: study of two clinical cases.

    Directory of Open Access Journals (Sweden)

    Cecilia Suarez

    Full Text Available Gliomas are the most common primary brain tumors and yet almost incurable due mainly to their great invasion capability. This represents a challenge to present clinical oncology. Here, we introduce a mathematical model aiming to improve tumor spreading capability definition. The model consists in a time dependent reaction-diffusion equation in a three-dimensional spatial domain that distinguishes between different brain topological structures. The model uses a series of digitized images from brain slices covering the whole human brain. The Talairach atlas included in the model describes brain structures at different levels. Also, the inclusion of the Brodmann areas allows prediction of the brain functions affected during tumor evolution and the estimation of correlated symptoms. The model is solved numerically using patient-specific parametrization and finite differences. Simulations consider an initial state with cellular proliferation alone (benign tumor, and an advanced state when infiltration starts (malign tumor. Survival time is estimated on the basis of tumor size and location. The model is used to predict tumor evolution in two clinical cases. In the first case, predictions show that real infiltrative areas are underestimated by current diagnostic imaging. In the second case, tumor spreading predictions were shown to be more accurate than those derived from previous models in the literature. Our results suggest that the inclusion of differential migration in glioma growth models constitutes another step towards a better prediction of tumor infiltration at the moment of surgical or radiosurgical target definition. Also, the addition of physiological/psychological considerations to classical anatomical models will provide a better and integral understanding of the patient disease at the moment of deciding therapeutic options, taking into account not only survival but also life quality.

  18. BrainK for Structural Image Processing: Creating Electrical Models of the Human Head

    Directory of Open Access Journals (Sweden)

    Kai Li

    2016-01-01

    Full Text Available BrainK is a set of automated procedures for characterizing the tissues of the human head from MRI, CT, and photogrammetry images. The tissue segmentation and cortical surface extraction support the primary goal of modeling the propagation of electrical currents through head tissues with a finite difference model (FDM or finite element model (FEM created from the BrainK geometries. The electrical head model is necessary for accurate source localization of dense array electroencephalographic (dEEG measures from head surface electrodes. It is also necessary for accurate targeting of cerebral structures with transcranial current injection from those surface electrodes. BrainK must achieve five major tasks: image segmentation, registration of the MRI, CT, and sensor photogrammetry images, cortical surface reconstruction, dipole tessellation of the cortical surface, and Talairach transformation. We describe the approach to each task, and we compare the accuracies for the key tasks of tissue segmentation and cortical surface extraction in relation to existing research tools (FreeSurfer, FSL, SPM, and BrainVisa. BrainK achieves good accuracy with minimal or no user intervention, it deals well with poor quality MR images and tissue abnormalities, and it provides improved computational efficiency over existing research packages.

  19. Dynamics of chaotic maps for modelling the multifractal spectrum of human brain Diffusion Tensor Images

    International Nuclear Information System (INIS)

    Provata, A.; Katsaloulis, P.; Verganelakis, D.A.

    2012-01-01

    Highlights: ► Calculation of human brain multifractal spectra. ► Calculations are based on Diffusion Tensor MRI Images. ► Spectra are modelled by coupled Ikeda map dynamics. ► Coupled lattice Ikeda maps model well only positive multifractal spectra. ► Appropriately modified coupled lattice Ikeda maps give correct spectra. - Abstract: The multifractal spectra of 3d Diffusion Tensor Images (DTI) obtained by magnetic resonance imaging of the human brain are studied. They are shown to deviate substantially from artificial brain images with the same white matter intensity. All spectra, obtained from 12 healthy subjects, show common characteristics indicating non-trivial moments of the intensity. To model the spectra the dynamics of the chaotic Ikeda map are used. The DTI multifractal spectra for positive q are best approximated by 3d coupled Ikeda maps in the fully developed chaotic regime. The coupling constants are as small as α = 0.01. These results reflect not only the white tissue non-trivial architectural complexity in the human brain, but also demonstrate the presence and importance of coupling between neuron axons. The architectural complexity is also mirrored by the deviations in the negative q-spectra, where the rare events dominate. To obtain a good agreement in the DTI negative q-spectrum of the brain with the Ikeda dynamics, it is enough to slightly modify the most rare events of the coupled Ikeda distributions. The representation of Diffusion Tensor Images with coupled Ikeda maps is not unique: similar conclusions are drawn when other chaotic maps (Tent, Logistic or Henon maps) are employed in the modelling of the neuron axons network.

  20. Data-Driven Extraction of a Nested Model of Human Brain Function.

    Science.gov (United States)

    Bolt, Taylor; Nomi, Jason S; Yeo, B T Thomas; Uddin, Lucina Q

    2017-07-26

    Decades of cognitive neuroscience research have revealed two basic facts regarding task-driven brain activation patterns. First, distinct patterns of activation occur in response to different task demands. Second, a superordinate, dichotomous pattern of activation/deactivation, is common across a variety of task demands. We explore the possibility that a hierarchical model incorporates these two observed brain activation phenomena into a unifying framework. We apply a latent variable approach, exploratory bifactor analysis, to a large set of human (both sexes) brain activation maps ( n = 108) encompassing cognition, perception, action, and emotion behavioral domains, to determine the potential existence of a nested structure of factors that underlie a variety of commonly observed activation patterns. We find that a general factor, associated with a superordinate brain activation/deactivation pattern, explained the majority of the variance (52.37%) in brain activation patterns. The bifactor analysis also revealed several subfactors that explained an additional 31.02% of variance in brain activation patterns, associated with different manifestations of the superordinate brain activation/deactivation pattern, each emphasizing different contexts in which the task demands occurred. Importantly, this nested factor structure provided better overall fit to the data compared with a non-nested factor structure model. These results point to a domain-general psychological process, representing a "focused awareness" process or "attentional episode" that is variously manifested according to the sensory modality of the stimulus and degree of cognitive processing. This novel model provides the basis for constructing a biologically informed, data-driven taxonomy of psychological processes. SIGNIFICANCE STATEMENT A crucial step in identifying how the brain supports various psychological processes is a well-defined categorization or taxonomy of psychological processes and their

  1. Generative models of rich clubs in Hebbian neuronal networks and large-scale human brain networks.

    Science.gov (United States)

    Vértes, Petra E; Alexander-Bloch, Aaron; Bullmore, Edward T

    2014-10-05

    Rich clubs arise when nodes that are 'rich' in connections also form an elite, densely connected 'club'. In brain networks, rich clubs incur high physical connection costs but also appear to be especially valuable to brain function. However, little is known about the selection pressures that drive their formation. Here, we take two complementary approaches to this question: firstly we show, using generative modelling, that the emergence of rich clubs in large-scale human brain networks can be driven by an economic trade-off between connection costs and a second, competing topological term. Secondly we show, using simulated neural networks, that Hebbian learning rules also drive the emergence of rich clubs at the microscopic level, and that the prominence of these features increases with learning time. These results suggest that Hebbian learning may provide a neuronal mechanism for the selection of complex features such as rich clubs. The neural networks that we investigate are explicitly Hebbian, and we argue that the topological term in our model of large-scale brain connectivity may represent an analogous connection rule. This putative link between learning and rich clubs is also consistent with predictions that integrative aspects of brain network organization are especially important for adaptive behaviour. © 2014 The Author(s) Published by the Royal Society. All rights reserved.

  2. A Generic Multi-Compartmental CNS Distribution Model Structure for 9 Drugs Allows Prediction of Human Brain Target Site Concentrations

    NARCIS (Netherlands)

    Yamamoto, Yumi; Valitalo, Pyry A.; van den Berg, Dirk-Jan; Hartman, Robin; van den Brink, Willem; Wong, Yin Cheong; Huntjens, Dymphy R.; Proost, Johannes H.; Vermeulen, An; Krauwinkel, Walter; Bakshi, Suruchi; Aranzana-Climent, Vincent; Marchand, Sandrine; Dahyot-Fizelier, Claire; Couet, William; Danhof, Meindert; van Hasselt, Johan G. C.; de lange, Elizabeth C. M.

    Purpose Predicting target site drug concentration in the brain is of key importance for the successful development of drugs acting on the central nervous system. We propose a generic mathematical model to describe the pharmacokinetics in brain compartments, and apply this model to predict human

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

    Science.gov (United States)

    2018-01-05

    theory -of- mind bilateral game with two types of computerized agents: with or without humanlike cues. At the second experiment, human subjects played...Electrophysiological activities in brain regions belonging to the theory -of- mind network correlated with perceived capability, especially when a machine...recorded fMRI or event-related potentials while subjects are playing two cognitive games. At the first experiment, human subjects played a theory -of- mind

  4. Using human brain imaging studies as a guide towards animal models of schizophrenia

    Science.gov (United States)

    BOLKAN, Scott S.; DE CARVALHO, Fernanda D.; KELLENDONK, Christoph

    2015-01-01

    Schizophrenia is a heterogeneous and poorly understood mental disorder that is presently defined solely by its behavioral symptoms. Advances in genetic, epidemiological and brain imaging techniques in the past half century, however, have significantly advanced our understanding of the underlying biology of the disorder. In spite of these advances clinical research remains limited in its power to establish the causal relationships that link etiology with pathophysiology and symptoms. In this context, animal models provide an important tool for causally testing hypotheses about biological processes postulated to be disrupted in the disorder. While animal models can exploit a variety of entry points towards the study of schizophrenia, here we describe an approach that seeks to closely approximate functional alterations observed with brain imaging techniques in patients. By modeling these intermediate pathophysiological alterations in animals, this approach offers an opportunity to (1) tightly link a single functional brain abnormality with its behavioral consequences, and (2) to determine whether a single pathophysiology can causally produce alterations in other brain areas that have been described in patients. In this review we first summarize a selection of well-replicated biological abnormalities described in the schizophrenia literature. We then provide examples of animal models that were studied in the context of patient imaging findings describing enhanced striatal dopamine D2 receptor function, alterations in thalamo-prefrontal circuit function, and metabolic hyperfunction of the hippocampus. Lastly, we discuss the implications of findings from these animal models for our present understanding of schizophrenia, and consider key unanswered questions for future research in animal models and human patients. PMID:26037801

  5. Brain Organization into Resting State Networks Emerges at Criticality on a Model of the Human Connectome

    Science.gov (United States)

    Haimovici, Ariel; Tagliazucchi, Enzo; Balenzuela, Pablo; Chialvo, Dante R.

    2013-04-01

    The relation between large-scale brain structure and function is an outstanding open problem in neuroscience. We approach this problem by studying the dynamical regime under which realistic spatiotemporal patterns of brain activity emerge from the empirically derived network of human brain neuroanatomical connections. The results show that critical dynamics unfolding on the structural connectivity of the human brain allow the recovery of many key experimental findings obtained from functional magnetic resonance imaging, such as divergence of the correlation length, the anomalous scaling of correlation fluctuations, and the emergence of large-scale resting state networks.

  6. Levels of detail analysis of microwave scattering from human head models for brain stroke detection

    Directory of Open Access Journals (Sweden)

    Awais Munawar Qureshi

    2017-11-01

    Full Text Available In this paper, we have presented a microwave scattering analysis from multiple human head models. This study incorporates different levels of detail in the human head models and its effect on microwave scattering phenomenon. Two levels of detail are taken into account; (i Simplified ellipse shaped head model (ii Anatomically realistic head model, implemented using 2-D geometry. In addition, heterogenic and frequency-dispersive behavior of the brain tissues has also been incorporated in our head models. It is identified during this study that the microwave scattering phenomenon changes significantly once the complexity of head model is increased by incorporating more details using magnetic resonance imaging database. It is also found out that the microwave scattering results match in both types of head model (i.e., geometrically simple and anatomically realistic, once the measurements are made in the structurally simplified regions. However, the results diverge considerably in the complex areas of brain due to the arbitrary shape interface of tissue layers in the anatomically realistic head model. After incorporating various levels of detail, the solution of subject microwave scattering problem and the measurement of transmitted and backscattered signals were obtained using finite element method. Mesh convergence analysis was also performed to achieve error free results with a minimum number of mesh elements and a lesser degree of freedom in the fast computational time. The results were promising and the E-Field values converged for both simple and complex geometrical models. However, the E-Field difference between both types of head model at the same reference point differentiated a lot in terms of magnitude. At complex location, a high difference value of 0.04236 V/m was measured compared to the simple location, where it turned out to be 0.00197 V/m. This study also contributes to provide a comparison analysis between the direct and iterative

  7. A multi-channel magnetic induction tomography measurement system for human brain model imaging

    International Nuclear Information System (INIS)

    Xu, Zheng; Luo, Haijun; He, Wei; He, Chuanhong; Song, Xiaodong; Zahng, Zhanglong

    2009-01-01

    This paper proposes a multi-channel magnetic induction tomography measurement system for biological conductivity imaging in a human brain model. A hemispherical glass bowl filled with a salt solution is used as the human brain model; meanwhile, agar blocks of different conductivity are placed in the solution to simulate the intracerebral hemorrhage. The excitation and detection coils are fixed co-axially, and the axial gradiometer is used as the detection coil in order to cancel the primary field. On the outer surface of the glass bowl, 15 sensor units are arrayed in two circles as measurement parts, and a single sensor unit for canceling the phase drift is placed beside the glass bowl. The phase sensitivity of our system is 0.204°/S m −1 with the excitation frequency of 120 kHz and the phase noise is in the range of −0.03° to +0.05°. Only the coaxial detection coil is available for each excitation coil; therefore, 15 phase data are collected in each measurement turn. Finally, the two-dimensional images of conductivity distribution are obtained using an interpolation algorithm. The frequency-varying experiment indicates that the imaging quality becomes better as the excitation frequency is increased

  8. A retinoic acid-enhanced, multicellular human blood-brain barrier model derived from stem cell sources

    Science.gov (United States)

    Lippmann, Ethan S.; Al-Ahmad, Abraham; Azarin, Samira M.; Palecek, Sean P.; Shusta, Eric V.

    2014-02-01

    Blood-brain barrier (BBB) models are often used to investigate BBB function and screen brain-penetrating therapeutics, but it has been difficult to construct a human model that possesses an optimal BBB phenotype and is readily scalable. To address this challenge, we developed a human in vitro BBB model comprising brain microvascular endothelial cells (BMECs), pericytes, astrocytes and neurons derived from renewable cell sources. First, retinoic acid (RA) was used to substantially enhance BBB phenotypes in human pluripotent stem cell (hPSC)-derived BMECs, particularly through adherens junction, tight junction, and multidrug resistance protein regulation. RA-treated hPSC-derived BMECs were subsequently co-cultured with primary human brain pericytes and human astrocytes and neurons derived from human neural progenitor cells (NPCs) to yield a fully human BBB model that possessed significant tightness as measured by transendothelial electrical resistance (~5,000 Ωxcm2). Overall, this scalable human BBB model may enable a wide range of neuroscience studies.

  9. Task decomposition: a framework for comparing diverse training models in human brain plasticity studies

    Directory of Open Access Journals (Sweden)

    Emily B. J. Coffey

    2013-10-01

    Full Text Available Training studies, in which the structural or functional neurophysiology is compared before and after expertise is acquired, are increasingly being used as models for understanding the human brain’s potential for reorganization. It is proving difficult to use these results to answer basic and important questions like how task training leads to both specific and general changes in behaviour and how these changes correspond with modifications in the brain. The main culprit is the diversity of paradigms used as complex task models. An assortment of activities ranging from juggling to deciphering Morse code has been reported. Even when working in the same general domain, few researchers use similar training models. New ways to meaningfully compare complex tasks are needed. We propose a method for characterizing and deconstructing the task requirements of complex training paradigms, which is suitable for application to both structural and functional neuroimaging studies. We believe this approach will aid brain plasticity research by making it easier to compare training paradigms, identify ‘missing puzzle pieces’, and encourage researchers to design training protocols to bridge these gaps.

  10. New Perspectives on the Brain Lesion Approach - Implications for Theoretical Models of Human Memory.

    NARCIS (Netherlands)

    Irish, Muireann; van Kesteren, M.T.R.

    2017-01-01

    Human lesion studies represent the cornerstone of modern day neuropsychology and provide an important adjunct to functional neuroimaging methods. The study of human lesion groups with damage to distinct regions of the brain permits the identification of underlying mechanisms and structures not only

  11. Allostasis and the Human Brain: Integrating Models of Stress from the Social and Life Sciences

    Science.gov (United States)

    Ganzel, Barbara L.; Morris, Pamela A.; Wethington, Elaine

    2010-01-01

    We draw on the theory of allostasis to develop an integrative model of the current stress process that highlights the brain as a dynamically adapting interface between the changing environment and the biological self. We review evidence that the core emotional regions of the brain constitute the primary mediator of the well-established association…

  12. New Perspectives on the Brain Lesion Approach - Implications for Theoretical Models of Human Memory.

    Science.gov (United States)

    Irish, Muireann; van Kesteren, Marlieke T R

    2018-03-15

    Human lesion studies represent the cornerstone of modern day neuropsychology and provide an important adjunct to functional neuroimaging methods. The study of human lesion groups with damage to distinct regions of the brain permits the identification of underlying mechanisms and structures not only associated with, but essential for, complex cognitive processes. Here, we consider a recent review by McCormick et al., 2018 in which the power of the lesion model approach is elegantly presented with respect to a host of sophisticated cognitive endeavors, including autobiographical memory, future thinking, spatial navigation, and decision-making. By comparing profiles of loss and sparing in hippocampal (HC) and ventromedial prefrontal cortex (vmPFC) lesion groups, the authors provide new insights into the underlying neuroarchitecture of these diverse cognitive functions. Building on this framework, we consider how vmPFC and HC degeneration, in the context of large-scale network dysfunction in dementia, impacts discrete facets of memory and social cognition. Notably, we find remarkable concordance between the available evidence in dementia and that of the HC and vmPFC lesion literature. We further assess the role of the prefrontal cortex in modulating aspects of spatial navigation and discuss the role of schema-related processing in the service of memory more broadly. Far from being obsolete, we contend that human lesion work occupies a crucial position in cognitive neuroscience and offers an array of exciting areas for future study within this field. Copyright © 2017 IBRO. Published by Elsevier Ltd. All rights reserved.

  13. Oxidative Stress and Protein Quality Control Systems in the Aged Canine Brain as a Model for Human Neurodegenerative Disorders

    Directory of Open Access Journals (Sweden)

    Mariarita Romanucci

    2015-01-01

    Full Text Available Aged dogs are considered the most suitable spontaneous animal model for studying normal aging and neurodegenerative diseases. Elderly canines naturally develop cognitive dysfunction and neuropathological hallmarks similar to those seen in humans, especially Alzheimer’s disease-like pathology. Pet dogs also share similar living conditions and diets to humans. Oxidative damage accumulates in the canine brain during aging, making dogs a valid model for translational antioxidant treatment/prevention studies. Evidence suggests the presence of detective protein quality control systems, involving ubiquitin-proteasome system (UPS and Heat Shock Proteins (HSPs, in the aged canine brain. Further studies on the canine model are needed to clarify the role of age-related changes in UPS activity and HSP expression in neurodegeneration in order to design novel treatment strategies, such as HSP-based therapies, aimed at improving chaperone defences against proteotoxic stress affecting brain during aging.

  14. Oxidative Stress and Protein Quality Control Systems in the Aged Canine Brain as a Model for Human Neurodegenerative Disorders.

    Science.gov (United States)

    Romanucci, Mariarita; Della Salda, Leonardo

    2015-01-01

    Aged dogs are considered the most suitable spontaneous animal model for studying normal aging and neurodegenerative diseases. Elderly canines naturally develop cognitive dysfunction and neuropathological hallmarks similar to those seen in humans, especially Alzheimer's disease-like pathology. Pet dogs also share similar living conditions and diets to humans. Oxidative damage accumulates in the canine brain during aging, making dogs a valid model for translational antioxidant treatment/prevention studies. Evidence suggests the presence of detective protein quality control systems, involving ubiquitin-proteasome system (UPS) and Heat Shock Proteins (HSPs), in the aged canine brain. Further studies on the canine model are needed to clarify the role of age-related changes in UPS activity and HSP expression in neurodegeneration in order to design novel treatment strategies, such as HSP-based therapies, aimed at improving chaperone defences against proteotoxic stress affecting brain during aging.

  15. Initial Attempts of Development and Characterization of an In Vitro Blood Brain Barrier Model Derived from Human Pluripotent Stem Cells

    DEFF Research Database (Denmark)

    Goldeman, Charlotte; Saaby, Lasse; Hall, Vanessa Jane

    The human blood brain barrier has yet to be successfully replicated as an in vitro model. One of the more promising approaches has been to develop an in vitro model derived from human pluripotent stem cells. However, as promising as this model may be, a successful replication of the differentiation...... method on different kinds of pluripotent stem cell lines have yet to be accomplished. We try to approach the promising method as described by Stebbins et al. (2015) to differentiate human pluripotent stem cells into brain like endothelial cells (BECs). Five different human pluripotent stem cell lines...... were screened for the possibility to differentiate into BECs. Tüb1159, Tüb16423, Bioni010-C, WTSli024-A and WTSli002-A stem cell lines were initially seeded on Matrigel cultured with mTESR1 media to confluence, then seeded on Matrigel as a single cell suspension. After two-three days of culture we...

  16. Differential effects of vascular endothelial growth factor A isoforms in a mouse brain metastasis model of human melanoma.

    NARCIS (Netherlands)

    Kusters, B.; Waal, R.M.W. de; Wesseling, P.; Verrijp, K.; Maass, C.N.; Heerschap, A.; Barentsz, J.O.; Sweep, C.G.J.; Ruiter, D.J.; Leenders, W.P.J.

    2003-01-01

    We reported previously that vascular endothelial growth factor isoform A (VEGF-A) expression by Mel57 human melanoma cells led to tumor progression in a murine brain metastasis model in an angiogenesis-independent fashion by dilation of co-opted, pre-existing vessels and concomitant enhanced blood

  17. Bridging animal and human models of exercise-induced brain plasticity

    Science.gov (United States)

    Voss, Michelle W.; Vivar, Carmen; Kramer, Arthur F.; van Praag, Henriette

    2015-01-01

    Significant progress has been made in understanding the neurobiological mechanisms through which exercise protects and restores the brain. In this feature review, we integrate animal and human research, examining physical activity effects across multiple levels of description (neurons up to inter-regional pathways). We evaluate the influence of exercise on hippocampal structure and function, addressing common themes such as spatial memory and pattern separation, brain structure and plasticity, neurotrophic factors, and vasculature. Areas of research focused more within species, such as hippocampal neurogenesis in rodents, also provide crucial insight into the protective role of physical activity. Overall, converging evidence suggests exercise benefits brain function and cognition across the mammalian lifespan, which may translate into reduced risk for Alzheimer’s disease (AD) in humans. PMID:24029446

  18. Is this a brain which I see before me? Modeling human neural development with pluripotent stem cells.

    Science.gov (United States)

    Suzuki, Ikuo K; Vanderhaeghen, Pierre

    2015-09-15

    The human brain is arguably the most complex structure among living organisms. However, the specific mechanisms leading to this complexity remain incompletely understood, primarily because of the poor experimental accessibility of the human embryonic brain. Over recent years, technologies based on pluripotent stem cells (PSCs) have been developed to generate neural cells of various types. While the translational potential of PSC technologies for disease modeling and/or cell replacement therapies is usually put forward as a rationale for their utility, they are also opening novel windows for direct observation and experimentation of the basic mechanisms of human brain development. PSC-based studies have revealed that a number of cardinal features of neural ontogenesis are remarkably conserved in human models, which can be studied in a reductionist fashion. They have also revealed species-specific features, which constitute attractive lines of investigation to elucidate the mechanisms underlying the development of the human brain, and its link with evolution. © 2015. Published by The Company of Biologists Ltd.

  19. Normative human brain volume growth.

    Science.gov (United States)

    Peterson, Mallory; Warf, Benjamin C; Schiff, Steven J

    2018-03-02

    OBJECTIVE While there is a long history of interest in measuring brain growth, as of yet there is no definitive model for normative human brain volume growth. The goal of this study was to analyze a variety of candidate models for such growth and select the model that provides the most statistically applicable fit. The authors sought to optimize clinically applicable growth charts that would facilitate improved treatment and predictive management for conditions such as hydrocephalus. METHODS The Weibull, two-term power law, West ontogenic, and Gompertz models were chosen as potential models. Normative brain volume data were compiled from the NIH MRI repository, and the data were fit using a nonlinear least squares regression algorithm. Appropriate statistical measures were analyzed for each model, and the best model was characterized with prediction bound curves to provide percentile estimates for clinical use. RESULTS Each model curve fit and the corresponding statistics were presented and analyzed. The Weibull fit had the best statistical results for both males and females, while the two-term power law generated the worst scores. The statistical measures and goodness of fit parameters for each model were provided to assure reproducibility. CONCLUSIONS The authors identified the Weibull model as the most effective growth curve fit for both males and females. Clinically usable growth charts were developed and provided to facilitate further clinical study of brain volume growth in conditions such as hydrocephalus. The authors note that the homogenous population from which the normative MRI data were compiled limits the study. Gaining a better understanding of the dynamics that underlie childhood brain growth would yield more predictive growth curves and improved neurosurgical management of hydrocephalus.

  20. 3D active shape models of human brain structures: application to patient-specific mesh generation

    Science.gov (United States)

    Ravikumar, Nishant; Castro-Mateos, Isaac; Pozo, Jose M.; Frangi, Alejandro F.; Taylor, Zeike A.

    2015-03-01

    The use of biomechanics-based numerical simulations has attracted growing interest in recent years for computer-aided diagnosis and treatment planning. With this in mind, a method for automatic mesh generation of brain structures of interest, using statistical models of shape (SSM) and appearance (SAM), for personalised computational modelling is presented. SSMs are constructed as point distribution models (PDMs) while SAMs are trained using intensity profiles sampled from a training set of T1-weighted magnetic resonance images. The brain structures of interest are, the cortical surface (cerebrum, cerebellum & brainstem), lateral ventricles and falx-cerebri membrane. Two methods for establishing correspondences across the training set of shapes are investigated and compared (based on SSM quality): the Coherent Point Drift (CPD) point-set registration method and B-spline mesh-to-mesh registration method. The MNI-305 (Montreal Neurological Institute) average brain atlas is used to generate the template mesh, which is deformed and registered to each training case, to establish correspondence over the training set of shapes. 18 healthy patients' T1-weightedMRimages form the training set used to generate the SSM and SAM. Both model-training and model-fitting are performed over multiple brain structures simultaneously. Compactness and generalisation errors of the BSpline-SSM and CPD-SSM are evaluated and used to quantitatively compare the SSMs. Leave-one-out cross validation is used to evaluate SSM quality in terms of these measures. The mesh-based SSM is found to generalise better and is more compact, relative to the CPD-based SSM. Quality of the best-fit model instance from the trained SSMs, to test cases are evaluated using the Hausdorff distance (HD) and mean absolute surface distance (MASD) metrics.

  1. Kinetic modeling of 11C-SB207145 binding to 5-HT4 receptors in the human brain in vivo

    DEFF Research Database (Denmark)

    Marner, Lisbeth; Gillings, Nic; Comley, Robert A

    2009-01-01

    The serotonin 4 receptor (5-HT(4) receptor) is known to be involved in learning and memory. We evaluated for the first time the quantification of a novel 5-HT(4) receptor radioligand, (11)C-SB207145, for in vivo brain imaging with PET in humans. METHODS: For evaluation of reproducibility, 6...... region devoid of specific binding, and that nonspecific binding was constant across brain regions. CONCLUSION: In vivo imaging of cerebral 5-HT(4) receptors can be determined reliably using (11)C-207145 PET with arterial input in humans. SRTM showed high reproducibility and reliability but bias....... Regions of interest were delineated automatically on the individual's MR images coregistered to the PET images, and regional time-activity curves were extracted. Quantitative tracer kinetic modeling was investigated with 1- and 2-tissue-compartment models using plasma input functions and the simplified...

  2. Human brain tumors

    International Nuclear Information System (INIS)

    Heindel, W.; Luyten, P.R.; Herholz, K.; Marien, J.H.; Kugel, H.; Bunke, J.; Heiss, W.D.; Hollander, J.A. den.

    1990-01-01

    It has been postulated that malignant tumors show increased anaerobic glycolysis. Areas of increased glycolysis could be identified by detection of increased glucose uptake and lactate production. The purpose of this paper is to investigate whether the most active parts in human brain tumors can be localized by correlating findings of proton (H-1) spectroscopic imaging and fluorodeoxyglucose (FDG) positron emission tomography (PET). Localized H-1 MR spectroscopy was performed with a clinical 1.5-T whole-body MR system. In 15 patients with CH-1 gliomas, the spatial distribution of choline-containing compounds, creatine, N-acetyl aspartate (NAA), and lactate was displayed as spectroscopic images. Those metabolite maps were correlated with conventional MR images and, in five cases, with corresponding PET sections

  3. An introduction to human brain anatomy

    NARCIS (Netherlands)

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

    2015-01-01

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

  4. Gaussian mixture models and semantic gating improve reconstructions from human brain activity

    Directory of Open Access Journals (Sweden)

    Sanne eSchoenmakers

    2015-01-01

    Full Text Available Better acquisition protocols and analysis techniques are making it possible to use fMRI to obtain highly detailed visualizations of brain processes. In particular we focus on the reconstruction of natural images from BOLD responses in visual cortex. We expand our linear Gaussian framework for percept decoding with Gaussian mixture models to better represent the prior distribution of natural images. Reconstruction of such images then boils down to probabilistic inference in a hybrid Bayesian network. In our set-up, different mixture components correspond to different character categories. Our framework can automatically infer higher-order semantic categories from lower-level brain areas. Furthermore the framework can gate semantic information from higher-order brain areas to enforce the correct category during reconstruction. When categorical information is not available, we show that automatically learned clusters in the data give a similar improvement in reconstruction. The hybrid Bayesian network leads to highly accurate reconstructions in both supervised and unsupervised settings.

  5. Pathology of the Aging Brain in Domestic and Laboratory Animals, and Animal Models of Human Neurodegenerative Diseases.

    Science.gov (United States)

    Youssef, S A; Capucchio, M T; Rofina, J E; Chambers, J K; Uchida, K; Nakayama, H; Head, E

    2016-03-01

    According to the WHO, the proportion of people over 60 years is increasing and expected to reach 22% of total world's population in 2050. In parallel, recent animal demographic studies have shown that the life expectancy of pet dogs and cats is increasing. Brain aging is associated not only with molecular and morphological changes but also leads to different degrees of behavioral and cognitive dysfunction. Common age-related brain lesions in humans include brain atrophy, neuronal loss, amyloid plaques, cerebrovascular amyloid angiopathy, vascular mineralization, neurofibrillary tangles, meningeal osseous metaplasia, and accumulation of lipofuscin. In aging humans, the most common neurodegenerative disorder is Alzheimer's disease (AD), which progressively impairs cognition, behavior, and quality of life. Pathologic changes comparable to the lesions of AD are described in several other animal species, although their clinical significance and effect on cognitive function are poorly documented. This review describes the commonly reported age-associated neurologic lesions in domestic and laboratory animals and the relationship of these lesions to cognitive dysfunction. Also described are the comparative interspecies similarities and differences to AD and other human neurodegenerative diseases including Parkinson's disease and progressive supranuclear palsy, and the spontaneous and transgenic animal models of these diseases. © The Author(s) 2016.

  6. Global developmental gene expression and pathway analysis of normal brain development and mouse models of human neuronal migration defects.

    Directory of Open Access Journals (Sweden)

    Tiziano Pramparo

    2011-03-01

    Full Text Available Heterozygous LIS1 mutations are the most common cause of human lissencephaly, a human neuronal migration defect, and DCX mutations are the most common cause of X-linked lissencephaly. LIS1 is part of a protein complex including NDEL1 and 14-3-3ε that regulates dynein motor function and microtubule dynamics, while DCX stabilizes microtubules and cooperates with LIS1 during neuronal migration and neurogenesis. Targeted gene mutations of Lis1, Dcx, Ywhae (coding for 14-3-3ε, and Ndel1 lead to neuronal migration defects in mouse and provide models of human lissencephaly, as well as aid the study of related neuro-developmental diseases. Here we investigated the developing brain of these four mutants and wild-type mice using expression microarrays, bioinformatic analyses, and in vivo/in vitro experiments to address whether mutations in different members of the LIS1 neuronal migration complex lead to similar and/or distinct global gene expression alterations. Consistent with the overall successful development of the mutant brains, unsupervised clustering and co-expression analysis suggested that cell cycle and synaptogenesis genes are similarly expressed and co-regulated in WT and mutant brains in a time-dependent fashion. By contrast, focused co-expression analysis in the Lis1 and Ndel1 mutants uncovered substantial differences in the correlation among pathways. Differential expression analysis revealed that cell cycle, cell adhesion, and cytoskeleton organization pathways are commonly altered in all mutants, while synaptogenesis, cell morphology, and inflammation/immune response are specifically altered in one or more mutants. We found several commonly dysregulated genes located within pathogenic deletion/duplication regions, which represent novel candidates of human mental retardation and neurocognitive disabilities. Our analysis suggests that gene expression and pathway analysis in mouse models of a similar disorder or within a common pathway can

  7. Global developmental gene expression and pathway analysis of normal brain development and mouse models of human neuronal migration defects.

    Science.gov (United States)

    Pramparo, Tiziano; Libiger, Ondrej; Jain, Sonia; Li, Hong; Youn, Yong Ha; Hirotsune, Shinji; Schork, Nicholas J; Wynshaw-Boris, Anthony

    2011-03-01

    Heterozygous LIS1 mutations are the most common cause of human lissencephaly, a human neuronal migration defect, and DCX mutations are the most common cause of X-linked lissencephaly. LIS1 is part of a protein complex including NDEL1 and 14-3-3ε that regulates dynein motor function and microtubule dynamics, while DCX stabilizes microtubules and cooperates with LIS1 during neuronal migration and neurogenesis. Targeted gene mutations of Lis1, Dcx, Ywhae (coding for 14-3-3ε), and Ndel1 lead to neuronal migration defects in mouse and provide models of human lissencephaly, as well as aid the study of related neuro-developmental diseases. Here we investigated the developing brain of these four mutants and wild-type mice using expression microarrays, bioinformatic analyses, and in vivo/in vitro experiments to address whether mutations in different members of the LIS1 neuronal migration complex lead to similar and/or distinct global gene expression alterations. Consistent with the overall successful development of the mutant brains, unsupervised clustering and co-expression analysis suggested that cell cycle and synaptogenesis genes are similarly expressed and co-regulated in WT and mutant brains in a time-dependent fashion. By contrast, focused co-expression analysis in the Lis1 and Ndel1 mutants uncovered substantial differences in the correlation among pathways. Differential expression analysis revealed that cell cycle, cell adhesion, and cytoskeleton organization pathways are commonly altered in all mutants, while synaptogenesis, cell morphology, and inflammation/immune response are specifically altered in one or more mutants. We found several commonly dysregulated genes located within pathogenic deletion/duplication regions, which represent novel candidates of human mental retardation and neurocognitive disabilities. Our analysis suggests that gene expression and pathway analysis in mouse models of a similar disorder or within a common pathway can be used to define

  8. A Multi-Route Model of Nicotine-Cotinine Pharmacokinetics, Pharmacodynamics and Brain Nicotinic Acetylcholine Receptor Binding in Humans

    Energy Technology Data Exchange (ETDEWEB)

    Teeguarden, Justin G.; Housand, Conrad; Smith, Jordan N.; Hinderliter, Paul M.; Gunawan, Rudy; Timchalk, Charles

    2013-02-01

    The pharmacokinetics of nicotine, the pharmacologically active alkaloid in tobacco responsible for addiction, are well characterized in humans. We developed a physiologically based pharmacokinetic/pharmacodynamic model of nicotine pharmacokinetics, brain dosimetry and brain nicotinic acetylcholine receptor (nAChRs) occupancy. A Bayesian framework was applied to optimize model parameters against multiple human data sets. The resulting model was consistent with both calibration and test data sets, but in general underestimated variability. A pharmacodynamic model relating nicotine levels to increases in heart rate as a proxy for the pharmacological effects of nicotine accurately described the nicotine related changes in heart rate and the development and decay of tolerance to nicotine. The PBPK model was utilized to quantitatively capture the combined impact of variation in physiological and metabolic parameters, nicotine availability and smoking compensation on the change in number of cigarettes smoked and toxicant exposure in a population of 10,000 people presented with a reduced toxicant (50%), reduced nicotine (50%) cigarette Across the population, toxicant exposure is reduced in some but not all smokers. Reductions are not in proportion to reductions in toxicant yields, largely due to partial compensation in response to reduced nicotine yields. This framework can be used as a key element of a dosimetry-driven risk assessment strategy for cigarette smoke constituents.

  9. A network of networks model to study phase synchronization using structural connection matrix of human brain

    Science.gov (United States)

    Ferrari, F. A. S.; Viana, R. L.; Reis, A. S.; Iarosz, K. C.; Caldas, I. L.; Batista, A. M.

    2018-04-01

    The cerebral cortex plays a key role in complex cortical functions. It can be divided into areas according to their function (motor, sensory and association areas). In this paper, the cerebral cortex is described as a network of networks (cortex network), we consider that each cortical area is composed of a network with small-world property (cortical network). The neurons are assumed to have bursting properties with the dynamics described by the Rulkov model. We study the phase synchronization of the cortex network and the cortical networks. In our simulations, we verify that synchronization in cortex network is not homogeneous. Besides, we focus on the suppression of neural phase synchronization. Synchronization can be related to undesired and pathological abnormal rhythms in the brain. For this reason, we consider the delayed feedback control to suppress the synchronization. We show that delayed feedback control is efficient to suppress synchronous behavior in our network model when an appropriate signal intensity and time delay are defined.

  10. A combination of experimental measurement, constitutive damage model, and diffusion tensor imaging to characterize the mechanical properties of the human brain.

    Science.gov (United States)

    Karimi, Alireza; Rahmati, Seyed Mohammadali; Razaghi, Reza

    2017-09-01

    Understanding the mechanical properties of the human brain is deemed important as it may subject to various types of complex loadings during the Traumatic Brain Injury (TBI). Although many studies so far have been conducted to quantify the mechanical properties of the brain, there is a paucity of knowledge on the mechanical properties of the human brain tissue and the damage of its axon fibers under the various types of complex loadings during the Traumatic Brain Injury (TBI). Although many studies so far have been conducted to quantify the mechanical properties of the brain, there is a paucity of knowledge on the mechanical properties of the human brain tissue and the damage of its axon fibers under the frontal lobe of the human brain. The constrained nonlinear minimization method was employed to identify the brain coefficients according to the axial and transversal compressive data. The pseudo-elastic damage model data was also well compared with that of the experimental data and it not only up to the primary loading but also the discontinuous softening could well address the mechanical behavior of the brain tissue.

  11. Brain response to primary blast wave using validated finite element models of human head and advanced combat helmet

    Directory of Open Access Journals (Sweden)

    Liying eZhang

    2013-08-01

    Full Text Available Blast-induced traumatic brain injury has emerged as a signature injury in combat casualty care. Present combat helmets are designed primarily to protect against ballistic and blunt impacts, but the current issue with helmets is protection concerning blasts. In order to delineate the blast wave attenuating capability of the Advanced Combat Helmet (ACH, a finite element (FE study was undertaken to evaluate the head response against blast loadings with and without helmet using a partially validated FE model of the human head and ACH. Four levels of overpressures (0.27-0.66 MPa from the Bowen’s lung iso-damage threshold curves were used to simulate blast insults. Effectiveness of the helmet with respect to head orientation was also investigated. The resulting biomechanical responses of the brain to blast threats were compared for human head with and without the helmet. For all Bowen’s cases, the peak intracranial pressures (ICP in the head ranged from 0.68-1.8 MPa in the coup cortical region. ACH was found to mitigate ICP in the head by 10-35%. Helmeted head resulted in 30% lower average peak brain strains and product of strain and strain rate. Among three blast loading directions with ACH, highest reduction in peak ICP (44% was due to backward blasts whereas the lowest reduction in peak ICP and brain strains was due to forward blast (27%. The biomechanical responses of a human head to primary blast insult exhibited directional sensitivity owing to the different geometry contours and coverage of the helmet construction and asymmetric anatomy of the head. Thus, direction-specific tolerances are needed in helmet design in order to offer omni-directional protection for the human head. The blasts of varying peak overpressures and durations that are believed to produce the same level of lung injury produce different levels of mechanical responses in the brain, and hence "iso-damage" curves for brain injury are likely different than the Bowen curves

  12. Modeling Structural Brain Connectivity

    DEFF Research Database (Denmark)

    Ambrosen, Karen Marie Sandø

    The human brain consists of a gigantic complex network of interconnected neurons. Together all these connections determine who we are, how we react and how we interpret the world. Knowledge about how the brain is connected can further our understanding of the brain’s structural organization, help...... improve diagnosis, and potentially allow better treatment of a wide range of neurological disorders. Tractography based on diffusion magnetic resonance imaging is a unique tool to estimate this “structural connectivity” of the brain non-invasively and in vivo. During the last decade, brain connectivity...... has increasingly been analyzed using graph theoretic measures adopted from network science and this characterization of the brain’s structural connectivity has been shown to be useful for the classification of populations, such as healthy and diseased subjects. The structural connectivity of the brain...

  13. Three-compartment modeling of C-11 N-Methyl spiperone kinetics in the human brain

    International Nuclear Information System (INIS)

    Brooks, R.A.; Wong, D.F.; Di Chiro, G.; Wayner, R.T.; Douglass, K.H.; Frost, J.J.; Larson, S.M.; Wagner, H.N. Jr.

    1984-01-01

    N-Methyl spiperone, as well as spiperone, has been used to study the dopamine receptor system in the brain. The authors have applied a 3-compartment model consisting of vascular, extravascular unbound, and receptor-bound activity to two normal volunteers and one patient with Parkinson's disease. The model differs from that proposed by another study, in that, as in the Sokoloff model for deoxyglucose, there is no explicit term for blood flow. Furthermore, the authors used a 3-compartment model for the cerebellum as well as the caudate/putamen. Serial scans were obtained by PET for up to 2 hrs after injection of the tracer. Time-activity curves were generated over the caudate, putamen and cerebellum. The results indicate a close fit of the observed data to the 3-compatment model. In the model, K1 represents the rate constant of delivery of the tracer in the tissue from the vascular compartment. K2 is the reverse rate constant. K1 was approximately equal to K2 for the cerebellum. In the basal ganglia, K2 was less than K1 due to nonspecific binding in compartment 2. K3 represents the rate constant of binding of the tracer to the receptor binding sites in the cerebral cortex and basal ganglia and to nonspecific binding sites in the cerebellum which contains essentially no dopamine receptors. K4 represents the rate constant for dissociation of the tracer from the receptors. For N-methyl spiperone K4 is very low in the caudate/putamen. The 3-compartment model seemed to fit the data better than the 2-compartment model for both the caudate/putamen and cerebellar activity

  14. Brain Network Modelling

    DEFF Research Database (Denmark)

    Andersen, Kasper Winther

    Three main topics are presented in this thesis. The first and largest topic concerns network modelling of functional Magnetic Resonance Imaging (fMRI) and Diffusion Weighted Imaging (DWI). In particular nonparametric Bayesian methods are used to model brain networks derived from resting state f...... for their ability to reproduce node clustering and predict unseen data. Comparing the models on whole brain networks, BCD and IRM showed better reproducibility and predictability than IDM, suggesting that resting state networks exhibit community structure. This also points to the importance of using models, which...... allow for complex interactions between all pairs of clusters. In addition, it is demonstrated how the IRM can be used for segmenting brain structures into functionally coherent clusters. A new nonparametric Bayesian network model is presented. The model builds upon the IRM and can be used to infer...

  15. Human brain mapping: Experimental and computational approaches

    Energy Technology Data Exchange (ETDEWEB)

    Wood, C.C.; George, J.S.; Schmidt, D.M.; Aine, C.J. [Los Alamos National Lab., NM (US); Sanders, J. [Albuquerque VA Medical Center, NM (US); Belliveau, J. [Massachusetts General Hospital, Boston, MA (US)

    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.

  16. Glucose metabolism via the pentose phosphate pathway, glycolysis and Krebs cycle in an orthotopic mouse model of human brain tumors.

    Science.gov (United States)

    Marin-Valencia, Isaac; Cho, Steve K; Rakheja, Dinesh; Hatanpaa, Kimmo J; Kapur, Payal; Mashimo, Tomoyuki; Jindal, Ashish; Vemireddy, Vamsidhara; Good, Levi B; Raisanen, Jack; Sun, Xiankai; Mickey, Bruce; Choi, Changho; Takahashi, Masaya; Togao, Osamu; Pascual, Juan M; Deberardinis, Ralph J; Maher, Elizabeth A; Malloy, Craig R; Bachoo, Robert M

    2012-10-01

    It has been hypothesized that increased flux through the pentose phosphate pathway (PPP) is required to support the metabolic demands of rapid malignant cell growth. Using orthotopic mouse models of human glioblastoma (GBM) and renal cell carcinoma metastatic to brain, we estimated the activity of the PPP relative to glycolysis by infusing [1,2-(13) C(2) ]glucose. The [3-(13) C]lactate/[2,3-(13) C(2) ]lactate ratio was similar for both the GBM and brain metastasis and their respective surrounding brains (GBM, 0.197 ± 0.011 and 0.195 ± 0.033, respectively (p = 1); metastasis: 0.126 and 0.119 ± 0.033, respectively). This suggests that the rate of glycolysis is significantly greater than the PPP flux in these tumors, and that the PPP flux into the lactate pool is similar in both tumors. Remarkably, (13) C-(13) C coupling was observed in molecules derived from Krebs cycle intermediates in both tumor types, denoting glucose oxidation. In the renal cell carcinoma, in contrast with GBM, (13) C multiplets of γ-aminobutyric acid (GABA) differed from its precursor glutamate, suggesting that GABA did not derive from a common glutamate precursor pool. In addition, the orthotopic renal tumor, the patient's primary renal mass and brain metastasis were all strongly immunopositive for the 67-kDa isoform of glutamate decarboxylase, as were 84% of tumors on a renal cell carcinoma tissue microarray of the same histology, suggesting that GABA synthesis is cell autonomous in at least a subset of renal cell carcinomas. Taken together, these data demonstrate that (13) C-labeled glucose can be used in orthotopic mouse models to study tumor metabolism in vivo and to ascertain new metabolic targets for cancer diagnosis and therapy. Copyright © 2012 John Wiley & Sons, Ltd.

  17. Model-free functional MRI analysis for detecting low-frequency functional connectivity in the human brain

    Science.gov (United States)

    Wismueller, Axel; Lange, Oliver; Auer, Dorothee; Leinsinger, Gerda

    2010-03-01

    Slowly varying temporally correlated activity fluctuations between functionally related brain areas have been identified by functional magnetic resonance imaging (fMRI) research in recent years. These low-frequency oscillations of less than 0.08 Hz appear to play a major role in various dynamic functional brain networks, such as the so-called 'default mode' network. They also have been observed as a property of symmetric cortices, and they are known to be present in the motor cortex among others. These low-frequency data are difficult to detect and quantify in fMRI. Traditionally, user-based regions of interests (ROI) or 'seed clusters' have been the primary analysis method. In this paper, we propose unsupervised clustering algorithms based on various distance measures to detect functional connectivity in resting state fMRI. The achieved results are evaluated quantitatively for different distance measures. The Euclidian metric implemented by standard unsupervised clustering approaches is compared with a non-metric topographic mapping of proximities based on the the mutual prediction error between pixel-specific signal dynamics time-series. It is shown that functional connectivity in the motor cortex of the human brain can be detected based on such model-free analysis methods for resting state fMRI.

  18. Development of Realistic Head Models for Electromagnetic Source Imaging of the Human Brain

    National Research Council Canada - National Science Library

    Akalin, Z

    2001-01-01

    ... images is performed Then triangular, quadratic meshes are formed for the interfaces of the tissues, Thus, realistic meshes, representing scalp, skull, CSF, brain and eye tissues, are formed, At least...

  19. Why did humans develop a large brain?

    OpenAIRE

    Muscat Baron, Yves

    2012-01-01

    "Of all animals, man has the largest brain in proportion to his size"- Aristotle. Dr Yves Muscat Baron shares his theory on how humans evolved large brains. The theory outlines how gravity could have helped humans develop a large brain- the author has named the theory 'The Gravitational Vascular Theory'. http://www.um.edu.mt/think/why-did-humans-develop-a-large-brain/

  20. Phosphatidylserine and the human brain.

    Science.gov (United States)

    Glade, Michael J; Smith, Kyl

    2015-06-01

    The aim of this study was to assess the roles and importance of phosphatidylserine (PS), an endogenous phospholipid and dietary nutrient, in human brain biochemistry, physiology, and function. A scientific literature search was conducted on MEDLINE for relevant articles regarding PS and the human brain published before June 2014. Additional publications were identified from references provided in original papers; 127 articles were selected for inclusion in this review. A large body of scientific evidence describes the interactions among PS, cognitive activity, cognitive aging, and retention of cognitive functioning ability. Phosphatidylserine is required for healthy nerve cell membranes and myelin. Aging of the human brain is associated with biochemical alterations and structural deterioration that impair neurotransmission. Exogenous PS (300-800 mg/d) is absorbed efficiently in humans, crosses the blood-brain barrier, and safely slows, halts, or reverses biochemical alterations and structural deterioration in nerve cells. It supports human cognitive functions, including the formation of short-term memory, the consolidation of long-term memory, the ability to create new memories, the ability to retrieve memories, the ability to learn and recall information, the ability to focus attention and concentrate, the ability to reason and solve problems, language skills, and the ability to communicate. It also supports locomotor functions, especially rapid reactions and reflexes. Copyright © 2015 Elsevier Inc. All rights reserved.

  1. Revisiting Glycogen Content in the Human Brain.

    Science.gov (United States)

    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.

  2. Modeling Pediatric Brain Trauma: Piglet Model of Controlled Cortical Impact.

    Science.gov (United States)

    Pareja, Jennifer C Munoz; Keeley, Kristen; Duhaime, Ann-Christine; Dodge, Carter P

    2016-01-01

    The brain has different responses to traumatic injury as a function of its developmental stage. As a model of injury to the immature brain, the piglet shares numerous similarities in regards to morphology and neurodevelopmental sequence compared to humans. This chapter describes a piglet scaled focal contusion model of traumatic brain injury that accounts for the changes in mass and morphology of the brain as it matures, facilitating the study of age-dependent differences in response to a comparable mechanical trauma.

  3. Diffusion MRI microstructure models with in vivo human brain Connectome data: results from a multi-group comparison.

    Science.gov (United States)

    Ferizi, Uran; Scherrer, Benoit; Schneider, Torben; Alipoor, Mohammad; Eufracio, Odin; Fick, Rutger H J; Deriche, Rachid; Nilsson, Markus; Loya-Olivas, Ana K; Rivera, Mariano; Poot, Dirk H J; Ramirez-Manzanares, Alonso; Marroquin, Jose L; Rokem, Ariel; Pötter, Christian; Dougherty, Robert F; Sakaie, Ken; Wheeler-Kingshott, Claudia; Warfield, Simon K; Witzel, Thomas; Wald, Lawrence L; Raya, José G; Alexander, Daniel C

    2017-09-01

    A large number of mathematical models have been proposed to describe the measured signal in diffusion-weighted (DW) magnetic resonance imaging (MRI). However, model comparison to date focuses only on specific subclasses, e.g. compartment models or signal models, and little or no information is available in the literature on how performance varies among the different types of models. To address this deficiency, we organized the 'White Matter Modeling Challenge' during the International Symposium on Biomedical Imaging (ISBI) 2015 conference. This competition aimed to compare a range of different kinds of models in their ability to explain a large range of measurable in vivo DW human brain data. Specifically, we assessed the ability of models to predict the DW signal accurately for new diffusion gradients and b values. We did not evaluate the accuracy of estimated model parameters, as a ground truth is hard to obtain. We used the Connectome scanner at the Massachusetts General Hospital, using gradient strengths of up to 300 mT/m and a broad set of diffusion times. We focused on assessing the DW signal prediction in two regions: the genu in the corpus callosum, where the fibres are relatively straight and parallel, and the fornix, where the configuration of fibres is more complex. The challenge participants had access to three-quarters of the dataset and their models were ranked on their ability to predict the remaining unseen quarter of the data. The challenge provided a unique opportunity for a quantitative comparison of diverse methods from multiple groups worldwide. The comparison of the challenge entries reveals interesting trends that could potentially influence the next generation of diffusion-based quantitative MRI techniques. The first is that signal models do not necessarily outperform tissue models; in fact, of those tested, tissue models rank highest on average. The second is that assuming a non-Gaussian (rather than purely Gaussian) noise model provides

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

    Science.gov (United States)

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

    2016-07-03

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

  5. Fetal brain development in chimpanzees versus humans.

    OpenAIRE

    Sakai, Tomoko; Hirata, Satoshi; Fuwa, Kohki; Sugama, Keiko; Kusunoki, Kiyo; Makishima, Haruyuki; Eguchi, Tatsuya; Yamada, Shigehito; Ogihara, Naomichi; Takeshita, Hideko

    2012-01-01

    It is argued that the extraordinary brain enlargement observed in humans is due to not only the human-specific pattern of postnatal brain development, but also to that of prenatal brain development [1, 2]. However, the prenatal trajectory of brain development has not been explored in chimpanzees (Pan troglodytes), even though they are our closest living relatives. To address this lack of information, we tracked fetal development of the chimpanzee brain from approximately 14 to 34 weeks of ges...

  6. Inflammation Following Traumatic Brain Injury in Humans: Insights from Data-Driven and Mechanistic Models into Survival and Death

    Directory of Open Access Journals (Sweden)

    Andrew Abboud

    2016-09-01

    Full Text Available Inflammation induced by traumatic brain injury (TBI is a complex mediator of morbidity and mortality. We have previously demonstrated the utility of both data-driven and mechanistic models in settings of traumatic injury. We hypothesized that differential dynamic inflammation programs characterize TBI survivors vs. non-survivors, and sought to leverage computational modeling to derive novel insights into this life/death bifurcation. Thirteen inflammatory cytokines and chemokines were determined using Luminex™ in serial cerebrospinal fluid (CSF samples from 31 TBI patients over 5 days. In this cohort, 5 were non-survivors (Glasgow Outcome Scale [GOS] score = 1 and 26 were survivors (GOS > 1. A Pearson correlation analysis of initial injury (Glasgow Coma Scale [GCS] vs. GOS suggested that survivors and non-survivors had distinct clinical response trajectories to injury. Statistically significant differences in interleukin (IL-4, IL-5, IL-6, IL-8, IL-13, and tumor necrosis factor-α (TNF-α were observed between TBI survivors vs. non-survivors over 5 days. Principal Component Analysis and Dynamic Bayesian Network inference suggested differential roles of chemokines, TNF-α, IL-6, and IL-10, based upon which an ordinary differential equation model of TBI was generated. This model was calibrated separately to the time course data of TBI survivors vs. non-survivors as a function of initial GCS. Analysis of parameter values in ensembles of simulations from these models suggested differences in microglial and damage responses in TBI survivors vs. non-survivors. These studies suggest the utility of combined data-driven and mechanistic models in the context of human TBI.

  7. Brain connections of words, perceptions and actions: A neurobiological model of spatio-temporal semantic activation in the human cortex.

    Science.gov (United States)

    Tomasello, Rosario; Garagnani, Max; Wennekers, Thomas; Pulvermüller, Friedemann

    2017-04-01

    Neuroimaging and patient studies show that different areas of cortex respectively specialize for general and selective, or category-specific, semantic processing. Why are there both semantic hubs and category-specificity, and how come that they emerge in different cortical regions? Can the activation time-course of these areas be predicted and explained by brain-like network models? In this present work, we extend a neurocomputational model of human cortical function to simulate the time-course of cortical processes of understanding meaningful concrete words. The model implements frontal and temporal cortical areas for language, perception, and action along with their connectivity. It uses Hebbian learning to semantically ground words in aspects of their referential object- and action-related meaning. Compared with earlier proposals, the present model incorporates additional neuroanatomical links supported by connectivity studies and downscaled synaptic weights in order to control for functional between-area differences purely due to the number of in- or output links of an area. We show that learning of semantic relationships between words and the objects and actions these symbols are used to speak about, leads to the formation of distributed circuits, which all include neuronal material in connector hub areas bridging between sensory and motor cortical systems. Therefore, these connector hub areas acquire a role as semantic hubs. By differentially reaching into motor or visual areas, the cortical distributions of the emergent 'semantic circuits' reflect aspects of the represented symbols' meaning, thus explaining category-specificity. The improved connectivity structure of our model entails a degree of category-specificity even in the 'semantic hubs' of the model. The relative time-course of activation of these areas is typically fast and near-simultaneous, with semantic hubs central to the network structure activating before modality-preferential areas carrying

  8. A neonatal piglet model for investigating brain and cognitive development in small for gestational age human infants.

    Directory of Open Access Journals (Sweden)

    Emily C Radlowski

    Full Text Available The piglet was investigated as a potential model for studying brain and cognitive deficits associated with being born small for gestational age (SGA. Naturally farrowed SGA (0.7-1.0 kg BW and average for gestational age (AGA, 1.3-1.6 kg BW piglets were obtained on postnatal day (PD 2, placed in individual cages, and provided a nutritionally adequate milk replacer diet (285 ml/kg/d. Beginning at PD14, performance in a spatial T-maze task was assessed. At PD28, piglets were anesthetized for magnetic resonance (MR imaging to assess brain structure (voxel-based morphometry, connectivity (diffusion-tensor imaging and metabolites in the hippocampus and corpus callosum (proton MR spectroscopy. Piglets born SGA showed compensatory growth such that BW of SGA and AGA piglets was similar (P>0.05, by PD15. Birth weight affected maze performance, with SGA piglets taking longer to reach criterion than AGA piglets (p<0.01. Total brain volume of SGA and AGA piglets was similar (P<0.05, but overall, SGA piglets had less gray matter than AGA piglets (p<0.01 and tended to have a smaller internal capsule (p = 0.07. Group comparisons between SGA and AGA piglets defined 9 areas (≥ 20 clusters where SGA piglets had less white matter (p<0.01; 2 areas where SGA piglets had more white matter (p<0.01; and 3 areas where SGA piglets had more gray matter (p<0.01. The impact of being born SGA on white matter was supported by a lower (p<0.04 fractional anisotropy value for SGA piglets, suggesting reduced white matter development and connectivity. None of the metabolites measured were different between groups. Collectively, the results show that SGA piglets have spatial learning deficits and abnormal development of white matter. As learning deficits and abnormalities in white matter are common in SGA human infants, the piglet is a tractable translational model that can be used to investigate SGA-associated cognitive deficits and potential interventions.

  9. Connectome imaging for mapping human brain pathways.

    Science.gov (United States)

    Shi, Y; Toga, A W

    2017-09-01

    With the fast advance of connectome imaging techniques, we have the opportunity of mapping the human brain pathways in vivo at unprecedented resolution. In this article we review the current developments of diffusion magnetic resonance imaging (MRI) for the reconstruction of anatomical pathways in connectome studies. We first introduce the background of diffusion MRI with an emphasis on the technical advances and challenges in state-of-the-art multi-shell acquisition schemes used in the Human Connectome Project. Characterization of the microstructural environment in the human brain is discussed from the tensor model to the general fiber orientation distribution (FOD) models that can resolve crossing fibers in each voxel of the image. Using FOD-based tractography, we describe novel methods for fiber bundle reconstruction and graph-based connectivity analysis. Building upon these novel developments, there have already been successful applications of connectome imaging techniques in reconstructing challenging brain pathways. Examples including retinofugal and brainstem pathways will be reviewed. Finally, we discuss future directions in connectome imaging and its interaction with other aspects of brain imaging research.

  10. Development of Realistic Head Models for Electromagnetic Source Imaging of the Human Brain

    National Research Council Canada - National Science Library

    Akalin, Z

    2001-01-01

    In this work, a methodology is developed to solve the forward problem of electromagnetic source imaging using realistic head models, For this purpose, first segmentation of the 3 dimensional MR head...

  11. Broadband criticality of human brain network synchronization.

    Science.gov (United States)

    Kitzbichler, Manfred G; Smith, Marie L; Christensen, Søren R; Bullmore, Ed

    2009-03-01

    Self-organized criticality is an attractive model for human brain dynamics, but there has been little direct evidence for its existence in large-scale systems measured by neuroimaging. In general, critical systems are associated with fractal or power law scaling, long-range correlations in space and time, and rapid reconfiguration in response to external inputs. Here, we consider two measures of phase synchronization: the phase-lock interval, or duration of coupling between a pair of (neurophysiological) processes, and the lability of global synchronization of a (brain functional) network. Using computational simulations of two mechanistically distinct systems displaying complex dynamics, the Ising model and the Kuramoto model, we show that both synchronization metrics have power law probability distributions specifically when these systems are in a critical state. We then demonstrate power law scaling of both pairwise and global synchronization metrics in functional MRI and magnetoencephalographic data recorded from normal volunteers under resting conditions. These results strongly suggest that human brain functional systems exist in an endogenous state of dynamical criticality, characterized by a greater than random probability of both prolonged periods of phase-locking and occurrence of large rapid changes in the state of global synchronization, analogous to the neuronal "avalanches" previously described in cellular systems. Moreover, evidence for critical dynamics was identified consistently in neurophysiological systems operating at frequency intervals ranging from 0.05-0.11 to 62.5-125 Hz, confirming that criticality is a property of human brain functional network organization at all frequency intervals in the brain's physiological bandwidth.

  12. Native Mutant Huntingtin in Human Brain

    Science.gov (United States)

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

    2012-01-01

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

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

    Directory of Open Access Journals (Sweden)

    Chongyuan Luo

    2016-12-01

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

  14. What the human eye tells the brain: a new approach toward a hardware-based modeling of mental functions

    Science.gov (United States)

    Lauinger, N.

    2007-09-01

    A better understanding of intelligent information processing in human vision can be reached through a closer look at the macro- and micro-hardware available in the hierarchy of cortical processors along the main visual pathway connecting the retina, the CGL (corpus geniculatum laterale) and area V1 (cortical visual area 17). The building of the eye is driven by the brain and the engineering of the main visual pathway back to V1 seems to be driven by the eyes. The human eye offers to the brain much more intelligent information about the outer visible world than a camera producing flat 2D images on a CCD. Intelligent processing of visual information in human vision - a strong cooperation between eyes and brain - relays on axes related symmetry operations relevant for navigation in 4D spectral space-times, on a hierarchy of dynamically balanced equilibrium states, on diffractive-optical transformation of the Visible into RGB space, on range mapping based on RGB data (monocular and binocular 3D vision), on illuminant-adaptive optical correlations of local onto global RGB data (color constancy performances) and on invariant fourier-optical log-polar processing of image data (generic object classification; identification of objects). These performances are more compatible with optical processing of modern diffractive-optical sensors and interference-optical correlators than with cameras. The R+D project NAMIROS (Nano- and Micro-3D gratings for Optical Sensors) [8], coordinated by an interdisciplinary team of specialists at Corrsys 3D Sensors AG, describes the roadmap towards a technical realization of outstanding high-tech performances corresponding to human eye-brain co-processing.

  15. Coexpression networks identify brain region-specific enhancer RNAs in the human brain.

    Science.gov (United States)

    Yao, Pu; Lin, Peijie; Gokoolparsadh, Akira; Assareh, Amelia; Thang, Mike W C; Voineagu, Irina

    2015-08-01

    Despite major progress in identifying enhancer regions on a genome-wide scale, the majority of available data are limited to model organisms and human transformed cell lines. We have identified a robust set of enhancer RNAs (eRNAs) expressed in the human brain and constructed networks assessing eRNA-gene coexpression interactions across human fetal brain and multiple adult brain regions. Our data identify brain region-specific eRNAs and show that enhancer regions expressing eRNAs are enriched for genetic variants associated with autism spectrum disorders.

  16. Brain mechanisms underlying human communication

    Directory of Open Access Journals (Sweden)

    Matthijs L Noordzij

    2009-07-01

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

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

    Science.gov (United States)

    Koscik, Timothy R.; Tranel, Daniel

    2013-01-01

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

  18. REVISITING GLYCOGEN CONTENT IN THE HUMAN BRAIN

    OpenAIRE

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

    2015-01-01

    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 13C magnetic resonance spectroscopy (MRS) in conjunction with [1-13C]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, compl...

  19. Translational potential of human brain organoids.

    Science.gov (United States)

    Sun, Alfred X; Ng, Huck-Hui; Tan, Eng-King

    2018-02-01

    The recent technology of 3D cultures of cellular aggregates derived from human stem cells have led to the emergence of tissue-like structures of various organs including the brain. Brain organoids bear molecular and structural resemblance with developing human brains, and have been demonstrated to recapitulate several physiological and pathological functions of the brain. Here we provide an overview of the development of brain organoids for the clinical community, focusing on the current status of the field with an critical evaluation of its translational value.

  20. Use of anisotropic modelling in electrical impedance tomography: description of method and preliminary assessment of utility in imaging brain function in the adult human head.

    Science.gov (United States)

    Abascal, Juan-Felipe P J; Arridge, Simon R; Atkinson, David; Horesh, Raya; Fabrizi, Lorenzo; De Lucia, Marzia; Horesh, Lior; Bayford, Richard H; Holder, David S

    2008-11-01

    Electrical Impedance Tomography (EIT) is an imaging method which enables a volume conductivity map of a subject to be produced from multiple impedance measurements. It has the potential to become a portable non-invasive imaging technique of particular use in imaging brain function. Accurate numerical forward models may be used to improve image reconstruction but, until now, have employed an assumption of isotropic tissue conductivity. This may be expected to introduce inaccuracy, as body tissues, especially those such as white matter and the skull in head imaging, are highly anisotropic. The purpose of this study was, for the first time, to develop a method for incorporating anisotropy in a forward numerical model for EIT of the head and assess the resulting improvement in image quality in the case of linear reconstruction of one example of the human head. A realistic Finite Element Model (FEM) of an adult human head with segments for the scalp, skull, CSF, and brain was produced from a structural MRI. Anisotropy of the brain was estimated from a diffusion tensor-MRI of the same subject and anisotropy of the skull was approximated from the structural information. A method for incorporation of anisotropy in the forward model and its use in image reconstruction was produced. The improvement in reconstructed image quality was assessed in computer simulation by producing forward data, and then linear reconstruction using a sensitivity matrix approach. The mean boundary data difference between anisotropic and isotropic forward models for a reference conductivity was 50%. Use of the correct anisotropic FEM in image reconstruction, as opposed to an isotropic one, corrected an error of 24 mm in imaging a 10% conductivity decrease located in the hippocampus, improved localisation for conductivity changes deep in the brain and due to epilepsy by 4-17 mm, and, overall, led to a substantial improvement on image quality. This suggests that incorporation of anisotropy in

  1. Platelets alter gene expression profile in human brain endothelial cells in an in vitro model of cerebral malaria.

    Directory of Open Access Journals (Sweden)

    Mathieu Barbier

    Full Text Available Platelet adhesion to the brain microvasculature has been associated with cerebral malaria (CM in humans, suggesting that platelets play a role in the pathogenesis of this syndrome. In vitro co-cultures have shown that platelets can act as a bridge between Plasmodium falciparum-infected red blood cells (pRBC and human brain microvascular endothelial cells (HBEC and potentiate HBEC apoptosis. Using cDNA microarray technology, we analyzed transcriptional changes of HBEC in response to platelets in the presence or the absence of tumor necrosis factor (TNF and pRBC, which have been reported to alter gene expression in endothelial cells. Using a rigorous statistical approach with multiple test corrections, we showed a significant effect of platelets on gene expression in HBEC. We also detected a strong effect of TNF, whereas there was no transcriptional change induced specifically by pRBC. Nevertheless, a global ANOVA and a two-way ANOVA suggested that pRBC acted in interaction with platelets and TNF to alter gene expression in HBEC. The expression of selected genes was validated by RT-qPCR. The analysis of gene functional annotation indicated that platelets induce the expression of genes involved in inflammation and apoptosis, such as genes involved in chemokine-, TREM1-, cytokine-, IL10-, TGFβ-, death-receptor-, and apoptosis-signaling. Overall, our results support the hypothesis that platelets play a pathogenic role in CM.

  2. Tissue cultures from adult human postmortem subcortical brain areas

    NARCIS (Netherlands)

    Verwer, R. W. H.; Dubelaar, E. J. G.; Hermens, W. T. J. M. C.; Swaab, D. F.

    2002-01-01

    Animal models used to study human aging and neurodegeneration do not display all symptoms of these processes as they are found in humans. Recently, we have shown that many cells in neocortical slices from adult human postmortem brain may survive for extensive periods in vitro. Such cultures may

  3. Physical biology of human brain development

    Directory of Open Access Journals (Sweden)

    Silvia eBudday

    2015-07-01

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

  4. Opening the Blood-Brain Barrier with MR Imaging-guided Focused Ultrasound: Preclinical Testing on a Trans-Human Skull Porcine Model.

    Science.gov (United States)

    Huang, Yuexi; Alkins, Ryan; Schwartz, Michael L; Hynynen, Kullervo

    2017-01-01

    Purpose To develop and test a protocol in preparation for a clinical trial on opening the blood-brain barrier (BBB) with magnetic resonance (MR) imaging-guided focused ultrasound for the delivery of chemotherapy drugs to brain tumors. Materials and Methods The procedures were approved by the institutional animal care committee. A trans-human skull porcine model was designed for the preclinical testing. Wide craniotomies were applied in 11 pigs (weight, approximately 15 kg). A partial human skull was positioned over the animal's brain. A modified clinical MR imaging-guided focused ultrasound brain system was used with a 3.0-T MR unit. The ultrasound beam was steered during sonications over a 3 × 3 grid at 3-mm spacing. Acoustic power levels of 3-20 W were tested. Bolus injections of microbubbles at 4 μL/kg were tested for each sonication. Levels of BBB opening, hemorrhage, and cavitation signal were measured with MR imaging, histologic examination, and cavitation receivers, respectively. A cavitation safety algorithm was developed on the basis of logistic regression of the measurements and tested to minimize the risk of hemorrhage. Results BBB openings of approximately 1 cm 3 in volume were visualized with gadolinium-enhanced MR imaging after sonication at an acoustic power of approximately 5 W. Gross examination of histologic specimens helped confirm Evans blue (bound to macromolecule albumin) extravasation, and hematoxylin-eosin staining helped detect only scattered extravasation of red blood cells. In cases where cavitation signals were higher than thresholds, sonications were terminated immediately without causing hemorrhage. Conclusion With a trans-human skull porcine model, this study demonstrated BBB opening with a 230-kHz system in preparation for a clinical trial. © RSNA, 2016 Online supplemental material is available for this article.

  5. Male microchimerism in the human female brain.

    Science.gov (United States)

    Chan, William F N; Gurnot, Cécile; Montine, Thomas J; Sonnen, Joshua A; Guthrie, Katherine A; Nelson, J Lee

    2012-01-01

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

  6. Astrocyte calcium signal and gliotransmission in human brain tissue.

    Science.gov (United States)

    Navarrete, Marta; Perea, Gertrudis; Maglio, Laura; Pastor, Jesús; García de Sola, Rafael; Araque, Alfonso

    2013-05-01

    Brain function is recognized to rely on neuronal activity and signaling processes between neurons, whereas astrocytes are generally considered to play supportive roles for proper neuronal function. However, accumulating evidence indicates that astrocytes sense and control neuronal and synaptic activity, indicating that neuron and astrocytes reciprocally communicate. While this evidence has been obtained in experimental animal models, whether this bidirectional signaling between astrocytes and neurons occurs in human brain remains unknown. We have investigated the existence of astrocyte-neuron communication in human brain tissue, using electrophysiological and Ca(2+) imaging techniques in slices of the cortex and hippocampus obtained from biopsies from epileptic patients. Cortical and hippocampal human astrocytes displayed spontaneous Ca(2+) elevations that were independent of neuronal activity. Local application of transmitter receptor agonists or nerve electrical stimulation transiently elevated Ca(2+) in astrocytes, indicating that human astrocytes detect synaptic activity and respond to synaptically released neurotransmitters, suggesting the existence of neuron-to-astrocyte communication in human brain tissue. Electrophysiological recordings in neurons revealed the presence of slow inward currents (SICs) mediated by NMDA receptor activation. The frequency of SICs increased after local application of ATP that elevated astrocyte Ca(2+). Therefore, human astrocytes are able to release the gliotransmitter glutamate, which affect neuronal excitability through activation of NMDA receptors in neurons. These results reveal the existence of reciprocal signaling between neurons and astrocytes in human brain tissue, indicating that astrocytes are relevant in human neurophysiology and are involved in human brain function.

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

    Science.gov (United States)

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

    2017-05-04

    In vitro models of the developing brain such as three-dimensional brain organoids offer an unprecedented opportunity to study aspects of human brain development and disease. However, the cells generated within organoids and the extent to which they recapitulate the regional complexity, cellular diversity and circuit functionality of the brain remain undefined. Here we analyse gene expression in over 80,000 individual cells isolated from 31 human brain organoids. We find that organoids can generate a broad diversity of cells, which are related to endogenous classes, including cells from the cerebral cortex and the retina. Organoids could be developed over extended periods (more than 9 months), allowing for the establishment of relatively mature features, including the formation of dendritic spines and spontaneously active neuronal networks. Finally, neuronal activity within organoids could be controlled using light stimulation of photosensitive cells, which may offer a way to probe the functionality of human neuronal circuits using physiological sensory stimuli.

  8. Consumption of seaweeds and the human brain

    DEFF Research Database (Denmark)

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

    2017-01-01

    Much of the content of the human head is brain matter. This functions as the epicenter of human physical existence, including a sense of well-being and the manifestation of human consciousness. The human brain is a precious and complex organ which increases from 350 to 400 g in infants to 1......, the influences of environment, or in relation to genetic predisposition. The science of seaweeds, and particularly their broad range of applications, is gathering momentum as studies repeatedly underscore the natural health and nutritional benefits of dietary macroalgae. This article reviews research...... highlighting the potential impacts of the consumption of a variety of seaweeds on human brain health and includes theories in relation to the benefits to early Homo sapiens. The emphasis is on a varied diet including macroalgae and the gut/microbe/brain axis, the importance of polyunsaturated fatty acids...

  9. West Nile virus-induced cell adhesion molecules on human brain microvascular endothelial cells regulate leukocyte adhesion and modulate permeability of the in vitro blood-brain barrier model.

    Directory of Open Access Journals (Sweden)

    Kelsey Roe

    Full Text Available Characterizing the mechanisms by which West Nile virus (WNV causes blood-brain barrier (BBB disruption, leukocyte infiltration into the brain and neuroinflammation is important to understand the pathogenesis of WNV encephalitis. Here, we examined the role of endothelial cell adhesion molecules (CAMs in mediating the adhesion and transendothelial migration of leukocytes across human brain microvascular endothelial cells (HBMVE. Infection with WNV (NY99 strain significantly induced ICAM-1, VCAM-1, and E-selectin in human endothelial cells and infected mice brain, although the levels of their ligands on leukocytes (VLA-4, LFA-1and MAC-1 did not alter. The permeability of the in vitro BBB model increased dramatically following the transmigration of monocytes and lymphocytes across the models infected with WNV, which was reversed in the presence of a cocktail of blocking antibodies against ICAM-1, VCAM-1, and E-selectin. Further, WNV infection of HBMVE significantly increased leukocyte adhesion to the HBMVE monolayer and transmigration across the infected BBB model. The blockade of these CAMs reduced the adhesion and transmigration of leukocytes across the infected BBB model. Further, comparison of infection with highly neuroinvasive NY99 and non-lethal (Eg101 strain of WNV demonstrated similar level of virus replication and fold-increase of CAMs in HBMVE cells suggesting that the non-neuropathogenic response of Eg101 is not because of its inability to infect HBMVE cells. Collectively, these results suggest that increased expression of specific CAMs is a pathological event associated with WNV infection and may contribute to leukocyte infiltration and BBB disruption in vivo. Our data further implicate that strategies to block CAMs to reduce BBB disruption may limit neuroinflammation and virus-CNS entry via 'Trojan horse' route, and improve WNV disease outcome.

  10. West Nile virus-induced cell adhesion molecules on human brain microvascular endothelial cells regulate leukocyte adhesion and modulate permeability of the in vitro blood-brain barrier model.

    Science.gov (United States)

    Roe, Kelsey; Orillo, Beverly; Verma, Saguna

    2014-01-01

    Characterizing the mechanisms by which West Nile virus (WNV) causes blood-brain barrier (BBB) disruption, leukocyte infiltration into the brain and neuroinflammation is important to understand the pathogenesis of WNV encephalitis. Here, we examined the role of endothelial cell adhesion molecules (CAMs) in mediating the adhesion and transendothelial migration of leukocytes across human brain microvascular endothelial cells (HBMVE). Infection with WNV (NY99 strain) significantly induced ICAM-1, VCAM-1, and E-selectin in human endothelial cells and infected mice brain, although the levels of their ligands on leukocytes (VLA-4, LFA-1and MAC-1) did not alter. The permeability of the in vitro BBB model increased dramatically following the transmigration of monocytes and lymphocytes across the models infected with WNV, which was reversed in the presence of a cocktail of blocking antibodies against ICAM-1, VCAM-1, and E-selectin. Further, WNV infection of HBMVE significantly increased leukocyte adhesion to the HBMVE monolayer and transmigration across the infected BBB model. The blockade of these CAMs reduced the adhesion and transmigration of leukocytes across the infected BBB model. Further, comparison of infection with highly neuroinvasive NY99 and non-lethal (Eg101) strain of WNV demonstrated similar level of virus replication and fold-increase of CAMs in HBMVE cells suggesting that the non-neuropathogenic response of Eg101 is not because of its inability to infect HBMVE cells. Collectively, these results suggest that increased expression of specific CAMs is a pathological event associated with WNV infection and may contribute to leukocyte infiltration and BBB disruption in vivo. Our data further implicate that strategies to block CAMs to reduce BBB disruption may limit neuroinflammation and virus-CNS entry via 'Trojan horse' route, and improve WNV disease outcome.

  11. Transcranial magnetic stimulation and the human brain

    Science.gov (United States)

    Hallett, Mark

    2000-07-01

    Transcranial magnetic stimulation (TMS) is rapidly developing as a powerful, non-invasive tool for studying the human brain. A pulsed magnetic field creates current flow in the brain and can temporarily excite or inhibit specific areas. TMS of motor cortex can produce a muscle twitch or block movement; TMS of occipital cortex can produce visual phosphenes or scotomas. TMS can also alter the functioning of the brain beyond the time of stimulation, offering potential for therapy.

  12. Nasal application of HSV encoding human preproenkephalin blocks craniofacial pain in a rat model of traumatic brain injury

    DEFF Research Database (Denmark)

    Sørensen, Jens Christian Hedemann; Meidahl, Anders Christian Nørgaard; Tzabazis

    2017-01-01

    pain using nasal application of a herpes simplex virus (HSV)-based vector expressing human proenkephalin (SHPE) to target the trigeminal ganglia. Mild TBI was induced in rats by the use of a modified fluid percussion model. Two days after mild TBI, following the development of facial mechanical...

  13. In Vitro Modeling of Blood-Brain Barrier with Human iPSC-Derived Endothelial Cells, Pericytes, Neurons, and Astrocytes via Notch Signaling

    Directory of Open Access Journals (Sweden)

    Kohei Yamamizu

    2017-03-01

    Full Text Available The blood-brain barrier (BBB is composed of four cell populations, brain endothelial cells (BECs, pericytes, neurons, and astrocytes. Its role is to precisely regulate the microenvironment of the brain through selective substance crossing. Here we generated an in vitro model of the BBB by differentiating human induced pluripotent stem cells (hiPSCs into all four populations. When the four hiPSC-derived populations were co-cultured, endothelial cells (ECs were endowed with features consistent with BECs, including a high expression of nutrient transporters (CAT3, MFSD2A and efflux transporters (ABCA1, BCRP, PGP, MRP5, and strong barrier function based on tight junctions. Neuron-derived Dll1, which activates Notch signaling in ECs, was essential for the BEC specification. We performed in vitro BBB permeability tests and assessed ten clinical drugs by nanoLC-MS/MS, finding a good correlation with the BBB permeability reported in previous cases. This technology should be useful for research on human BBB physiology, pathology, and drug development.

  14. Ionising radiation and the developing human brain

    International Nuclear Information System (INIS)

    Schull, W.J.

    1991-01-01

    This article reviews the effects of radiation exposure of the developing human brain. Much of the evidence has come from the prenatally exposed in Hiroshima and Nagasaki. The effects on development age, mental retardation, head size, neuromuscular performance, intelligence tests, school performance and the occurrence of convulsions are discussed. Other topics covered include the biological nature of the damage to the brain, risk estimates in human and problems in radiation protection. (UK)

  15. Lactate fuels the human brain during exercise

    DEFF Research Database (Denmark)

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

    2008-01-01

    The human brain releases a small amount of lactate at rest, and even an increase in arterial blood lactate during anesthesia does not provoke a net cerebral lactate uptake. However, during cerebral activation associated with exercise involving a marked increase in plasma lactate, the brain takes up...... blockade but not with beta(1)-adrenergic blockade alone. Also, CMR decreases in response to epinephrine, suggesting that a beta(2)-adrenergic receptor mechanism enhances glucose and perhaps lactate transport across the blood-brain barrier. The pattern of CMR decrease under various forms of brain activation...

  16. The human connectome: A structural description of the human brain.

    Directory of Open Access Journals (Sweden)

    Olaf Sporns

    2005-09-01

    Full Text Available The connection matrix of the human brain (the human "connectome" represents an indispensable foundation for basic and applied neurobiological research. However, the network of anatomical connections linking the neuronal elements of the human brain is still largely unknown. While some databases or collations of large-scale anatomical connection patterns exist for other mammalian species, there is currently no connection matrix of the human brain, nor is there a coordinated research effort to collect, archive, and disseminate this important information. We propose a research strategy to achieve this goal, and discuss its potential impact.

  17. Analysis of a human brain transcriptome map

    Directory of Open Access Journals (Sweden)

    Greene Jonathan R

    2002-04-01

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

  18. Microphysiological Human Brain and Neural Systems-on-a-Chip: Potential Alternatives to Small Animal Models and Emerging Platforms for Drug Discovery and Personalized Medicine.

    Science.gov (United States)

    Haring, Alexander P; Sontheimer, Harald; Johnson, Blake N

    2017-06-01

    Translational challenges associated with reductionist modeling approaches, as well as ethical concerns and economic implications of small animal testing, drive the need for developing microphysiological neural systems for modeling human neurological diseases, disorders, and injuries. Here, we provide a comprehensive review of microphysiological brain and neural systems-on-a-chip (NSCs) for modeling higher order trajectories in the human nervous system. Societal, economic, and national security impacts of neurological diseases, disorders, and injuries are highlighted to identify critical NSC application spaces. Hierarchical design and manufacturing of NSCs are discussed with distinction for surface- and bulk-based systems. Three broad NSC classes are identified and reviewed: microfluidic NSCs, compartmentalized NSCs, and hydrogel NSCs. Emerging areas and future directions are highlighted, including the application of 3D printing to design and manufacturing of next-generation NSCs, the use of stem cells for constructing patient-specific NSCs, and the application of human NSCs to 'personalized neurology'. Technical hurdles and remaining challenges are discussed. This review identifies the state-of-the-art design methodologies, manufacturing approaches, and performance capabilities of NSCs. This work suggests NSCs appear poised to revolutionize the modeling of human neurological diseases, disorders, and injuries.

  19. Multivariate Heteroscedasticity Models for Functional Brain Connectivity

    Directory of Open Access Journals (Sweden)

    Christof Seiler

    2017-12-01

    Full Text Available Functional brain connectivity is the co-occurrence of brain activity in different areas during resting and while doing tasks. The data of interest are multivariate timeseries measured simultaneously across brain parcels using resting-state fMRI (rfMRI. We analyze functional connectivity using two heteroscedasticity models. Our first model is low-dimensional and scales linearly in the number of brain parcels. Our second model scales quadratically. We apply both models to data from the Human Connectome Project (HCP comparing connectivity between short and conventional sleepers. We find stronger functional connectivity in short than conventional sleepers in brain areas consistent with previous findings. This might be due to subjects falling asleep in the scanner. Consequently, we recommend the inclusion of average sleep duration as a covariate to remove unwanted variation in rfMRI studies. A power analysis using the HCP data shows that a sample size of 40 detects 50% of the connectivity at a false discovery rate of 20%. We provide implementations using R and the probabilistic programming language Stan.

  20. Transferrin Functionalized Liposomes Loading Dopamine HCl: Development and Permeability Studies across an In Vitro Model of Human Blood-Brain Barrier.

    Science.gov (United States)

    Lopalco, Antonio; Cutrignelli, Annalisa; Denora, Nunzio; Lopedota, Angela; Franco, Massimo; Laquintana, Valentino

    2018-03-20

    The transport of dopamine across the blood brain barrier represents a challenge for the management of Parkinson's disease. The employment of central nervous system targeted ligands functionalized nanocarriers could be a valid tactic to overcome this obstacle and avoid undesirable side effects. In this work, transferrin functionalized dopamine-loaded liposomes were made by a modified dehydration-rehydration technique from hydrogenated soy phosphatidylcoline, cholesterol and 1,2-stearoyl- sn -glycero-3-phosphoethanolamine- N -[carboxy(poly(ethylene glycol)-2000)]. The physical features of the prepared liposomes were established with successive determination of their endothelial permeability across an in vitro model of the blood-brain barrier, constituted by human cerebral microvascular endothelial cells (hCMEC/D3). Functionalized dopamine-loaded liposomes with encapsulation efficiency more than 35% were made with sizes in a range around 180 nm, polydispersity indices of 0.2, and positive zeta potential values (+7.5 mV). Their stability and drug release kinetics were also evaluated. The apparent permeability (P e ) values of encapsulated dopamine in functionalized and unfunctionalized liposomes showed that transferrin functionalized nanocarriers could represent appealing non-toxic candidates for brain delivery, thus improving benefits and decreasing complications to patients subjected to L-dopa chronical treatment.

  1. Network hubs in the human brain.

    Science.gov (United States)

    van den Heuvel, Martijn P; Sporns, Olaf

    2013-12-01

    Virtually all domains of cognitive function require the integration of distributed neural activity. Network analysis of human brain connectivity has consistently identified sets of regions that are critically important for enabling efficient neuronal signaling and communication. The central embedding of these candidate 'brain hubs' in anatomical networks supports their diverse functional roles across a broad range of cognitive tasks and widespread dynamic coupling within and across functional networks. The high level of centrality of brain hubs also renders them points of vulnerability that are susceptible to disconnection and dysfunction in brain disorders. Combining data from numerous empirical and computational studies, network approaches strongly suggest that brain hubs play important roles in information integration underpinning numerous aspects of complex cognitive function. Copyright © 2013 Elsevier Ltd. All rights reserved.

  2. Physiological and modeling evidence for focal transcranial electrical brain stimulation in humans: A basis for high-definition tDCS

    Science.gov (United States)

    Edwards, Dylan; Cortes, Mar; Datta, Abhishek; Minhas, Preet; Wassermann, Eric M.; Bikson, Marom

    2015-01-01

    Transcranial Direct Current Stimulation (tDCS) is a non-invasive, low-cost, well-tolerated technique producing lasting modulation of cortical excitability. Behavioral and therapeutic outcomes of tDCS are linked to the targeted brain regions, but there is little evidence that current reaches the brain as intended. We aimed to: (1) validate a computational model for estimating cortical electric fields in human transcranial stimulation, and (2) assess the magnitude and spread of cortical electric field with a novel High-Definition tDCS (HD-tDCS) scalp montage using a 4×1-Ring electrode configuration. In three healthy adults, Transcranial Electrical Stimulation (TES) over primary motor cortex (M1) was delivered using the 4×1 montage (4× cathode, surrounding a single central anode; montage radius ~3 cm) with sufficient intensity to elicit a discrete muscle twitch in the hand. The estimated current distribution in M1 was calculated using the individualized MRI-based model, and compared with the observed motor response across subjects. The response magnitude was quantified with stimulation over motor cortex as well as anterior and posterior to motor cortex. In each case the model data were consistent with the motor response across subjects. The estimated cortical electric fields with the 4×1 montage were compared (area, magnitude, direction) for TES and tDCS in each subject. We provide direct evidence in humans that TES with a 4×1-Ring configuration can activate motor cortex and that current does not substantially spread outside the stimulation area. Computational models predict that both TES and tDCS waveforms using the 4×1-Ring configuration generate electric fields in cortex with comparable gross current distribution, and preferentially directed normal (inward) currents. The agreement of modeling and experimental data for both current delivery and focality support the use of the HD-tDCS 4×1-Ring montage for cortically targeted neuromodulation. PMID:23370061

  3. Mathematical Model of Evolution of Brain Parcellation.

    Science.gov (United States)

    Ferrante, Daniel D; Wei, Yi; Koulakov, Alexei A

    2016-01-01

    We study the distribution of brain and cortical area sizes [parcellation units (PUs)] obtained for three species: mouse, macaque, and human. We find that the distribution of PU sizes is close to lognormal. We propose the mathematical model of evolution of brain parcellation based on iterative fragmentation and specialization. In this model, each existing PU has a probability to be split that depends on PU size only. This model suggests that the same evolutionary process may have led to brain parcellation in these three species. Within our model, region-to-region (macro) connectivity is given by the outer product form. We show that most experimental data on non-zero macaque cortex macroscopic-level connections can be explained by the outer product power-law form suggested by our model (62% for area V1). We propose a multiplicative Hebbian learning rule for the macroconnectome that could yield the correct scaling of connection strengths between areas. We thus propose an evolutionary model that may have contributed to both brain parcellation and mesoscopic level connectivity in mammals.

  4. Transcriptional Landscape of the Prenatal Human Brain

    Science.gov (United States)

    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

  5. Magnetic resonance spectroscopy of the human brain

    Science.gov (United States)

    Strózik-Kotlorz, D.

    2014-01-01

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

  6. Comparative Analysis of the Macroscale Structural Connectivity in the Macaque and Human Brain

    NARCIS (Netherlands)

    Goulas, A.; Bastiani, M.; Bezgin, G.; Uylings, H.B.M.; Roebroeck, A.; Stiers, P.

    2014-01-01

    The macaque brain serves as a model for the human brain, but its suitability is challenged by unique human features, including connectivity reconfigurations, which emerged during primate evolution. We perform a quantitative comparative analysis of the whole brain macroscale structural connectivity

  7. Brain mechanisms underlying human communication

    NARCIS (Netherlands)

    Noordzij, M.L.; Newman-Norlund, S.E.; Ruiter, J.P.A. de; Hagoort, P.; Levinson, S.C.; Toni, I.

    2009-01-01

    Human communication has been described as involving the coding-decoding of a conventional symbol system, which could be supported by parts of the human motor system (i.e. the "mirror neurons system"). However, this view does not explain how these conventions could develop in the first place. Here we

  8. Brain mechanisms underlying human communication

    NARCIS (Netherlands)

    Noordzij, Matthijs Leendert; Newman-Norlund, Sarah E.; de Ruiter, Jan Peter; Hagoort, Peter; Levinson, Stephen C.; Toni, Ivan

    2009-01-01

    Human communication has been described as involving the coding-decoding of a conventional symbol system, which could be supported by parts of the human motor system (i.e. the “mirror neurons system”). However, this view does not explain how these conventions could develop in the first place. Here we

  9. Cyto- and receptor architectonic mapping of the human brain.

    Science.gov (United States)

    Palomero-Gallagher, Nicola; Zilles, Karl

    2018-01-01

    Mapping of the human brain is more than the generation of an atlas-based parcellation of brain regions using histologic or histochemical criteria. It is the attempt to provide a topographically informed model of the structural and functional organization of the brain. To achieve this goal a multimodal atlas of the detailed microscopic and neurochemical structure of the brain must be registered to a stereotaxic reference space or brain, which also serves as reference for topographic assignment of functional data, e.g., functional magnet resonance imaging, electroencephalography, or magnetoencephalography, as well as metabolic imaging, e.g., positron emission tomography. Although classic maps remain pioneering steps, they do not match recent concepts of the functional organization in many regions, and suffer from methodic drawbacks. This chapter provides a summary of the recent status of human brain mapping, which is based on multimodal approaches integrating results of quantitative cyto- and receptor architectonic studies with focus on the cerebral cortex in a widely used reference brain. Descriptions of the methods for observer-independent and statistically testable cytoarchitectonic parcellations, quantitative multireceptor mapping, and registration to the reference brain, including the concept of probability maps and a toolbox for using the maps in functional neuroimaging studies, are provided. Copyright © 2018 Elsevier B.V. All rights reserved.

  10. Human brain evolution writ large and small.

    Science.gov (United States)

    Sherwood, Chet C; Bauernfeind, Amy L; Bianchi, Serena; Raghanti, Mary Ann; Hof, Patrick R

    2012-01-01

    Human evolution was marked by an extraordinary increase in total brain size relative to body size. While it is certain that increased encephalization is an important factor contributing to the origin of our species-specific cognitive abilities, it is difficult to disentangle which aspects of human neural structure and function are correlated by-products of brain size expansion from those that are specifically related to particular psychological specializations, such as language and enhanced "mentalizing" abilities. In this chapter, we review evidence from allometric scaling studies demonstrating that much of human neocortical organization can be understood as a product of brain enlargement. Defining extra-allometric specializations in humans is often hampered by a severe lack of comparative data from the same neuroanatomical variables across a broad range of primates. When possible, we highlight evidence for features of human neocortical architecture and function that cannot be easily explained as correlates of brain size and, hence, might be more directly associated with the evolution of uniquely human cognitive capacities. Copyright © 2012 Elsevier B.V. All rights reserved.

  11. Establishment of a Human Blood-Brain Barrier Co-culture Model Mimicking the Neurovascular Unit Using Induced Pluri- and Multipotent Stem Cells.

    Science.gov (United States)

    Appelt-Menzel, Antje; Cubukova, Alevtina; Günther, Katharina; Edenhofer, Frank; Piontek, Jörg; Krause, Gerd; Stüber, Tanja; Walles, Heike; Neuhaus, Winfried; Metzger, Marco

    2017-04-11

    In vitro models of the human blood-brain barrier (BBB) are highly desirable for drug development. This study aims to analyze a set of ten different BBB culture models based on primary cells, human induced pluripotent stem cells (hiPSCs), and multipotent fetal neural stem cells (fNSCs). We systematically investigated the impact of astrocytes, pericytes, and NSCs on hiPSC-derived BBB endothelial cell function and gene expression. The quadruple culture models, based on these four cell types, achieved BBB characteristics including transendothelial electrical resistance (TEER) up to 2,500 Ω cm 2 and distinct upregulation of typical BBB genes. A complex in vivo-like tight junction (TJ) network was detected by freeze-fracture and transmission electron microscopy. Treatment with claudin-specific TJ modulators caused TEER decrease, confirming the relevant role of claudin subtypes for paracellular tightness. Drug permeability tests with reference substances were performed and confirmed the suitability of the models for drug transport studies. Copyright © 2017 The Author(s). Published by Elsevier Inc. All rights reserved.

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

    Science.gov (United States)

    Buchweitz, Augusto; Prat, Chantel

    2013-12-01

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

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

    Science.gov (United States)

    Falk, Emily B; Bassett, Danielle S

    2017-09-01

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

  14. Visual dictionaries as intermediate features in the human brain

    Directory of Open Access Journals (Sweden)

    Kandan eRamakrishnan

    2015-01-01

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

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

    Science.gov (United States)

    Xia, Mingrui; Wang, Jinhui; He, Yong

    2013-01-01

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

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

    Directory of Open Access Journals (Sweden)

    Mingrui Xia

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

  17. Generation of human vascularized brain organoids.

    Science.gov (United States)

    Pham, Missy T; Pollock, Kari M; Rose, Melanie D; Cary, Whitney A; Stewart, Heather R; Zhou, Ping; Nolta, Jan A; Waldau, Ben

    2018-03-21

    The aim of this study was to vascularize brain organoids with a patient's own endothelial cells (ECs). Induced pluripotent stem cells (iPSCs) of one UC Davis patient were grown into whole-brain organoids. Simultaneously, iPSCs from the same patient were differentiated into ECs. On day 34, the organoid was re-embedded in Matrigel with 250 000 ECs. Vascularized organoids were grown in vitro for 3-5 weeks or transplanted into immunodeficient mice on day 54, and animals were perfused on day 68. Coating of brain organoids on day 34 with ECs led to robust vascularization of the organoid after 3-5 weeks in vitro and 2 weeks in vivo. Human CD31-positive blood vessels were found inside and in-between rosettes within the center of the organoid after transplantation. Vascularization of brain organoids with a patient's own iPSC-derived ECs is technically feasible.

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

    Science.gov (United States)

    Volkow, N D; Fowler, J S; Gatley, S J; Logan, J; Wang, G J; Ding, Y S; Dewey, 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 changes 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 neurological 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. Through the parallel development of new radiotracers, kinetic models and better instruments, PET technology is enabling investigation of increasingly more complex aspects of the human brain dopamine system. This paper summarizes the different tracers and experimental

  19. Pathology of the Aging Brain in Domestic and Laboratory Animals, and Animal Models of Human Neurodegenerative Diseases

    NARCIS (Netherlands)

    Youssef Hassan, Sameh; Capucchio, M T; Rofina, J E; Chambers, J K; Uchida, K; Nakayama, H; Head, E

    2016-01-01

    According to the WHO, the proportion of people over 60 years is increasing and expected to reach 22% of total world's population in 2050. In parallel, recent animal demographic studies have shown that the life expectancy of pet dogs and cats is increasing. Brain aging is associated not only with

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

    Science.gov (United States)

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

    2017-06-01

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

  1. A microfabricated microfluidic bioMEMS device to model human brain aneurisms: the aneurysm-on-a-chip

    Science.gov (United States)

    Reece, Lisa M.; Khor, Jian Wei; Thakur, Raviraj; Amin, Ahmed; Wereley, Steven T.; Leary, James F.

    2015-03-01

    Aneurysms are pockets of blood that collect outside blood vessel walls forming dilatations and leaving arterial walls very prone to rupture. There is little information concerning the causes of intracranial aneurysm formation, growth, and rupture. Current treatments include: (1) clipping, and (2) coil embolization, including stent-assisted coiling. Further, the evolution of any aneurysm is assumed to be caused by the remodeling of the affected blood vessel's material constituents (tunica intima, tunica media, or tunica adventitia). Velocity, pressure, and wall shear stresses aid in the disease development of aneurysmal growth, while the shear force mechanisms effecting wound closure are elusive. To study aneurysm pathogenesis, a lab-on-a-chip device is the key to discovering the underlying mechanisms of these lesions. A two-dimensional microfluidic model, the Aneurysm-on-a-Chip™ (AOC), was the logical answer to study particle flow within an aneurysm "sac". The AOC apparatus can track particles/cells when it is coupled to particle image velocimetry software (PIV) package. The AOC fluid flow was visualized using standard microscopy techniques with commercial microparticles and human aortic smooth muscle cells (HASMC). Images were taken during fluid flow experiments and PIV was utilized to monitor the flow of particles within the "sac" region, as well as particles entering and exiting the device. Quiver plots were generated from fluid flow experiments using standard 7 μm latex particles and fixed HASMC in PBS. PIV analysis shows that the particles flowed nicely from input to output. Wall shear stress provided evidence that there was some back flow at the edges of the "sac" - an indicator of aneurysm development in human patients.

  2. Hubs in the human fetal brain network

    NARCIS (Netherlands)

    van den Heuvel, M.I.; Turk, E.; Manning, J.H.; Hect, J.; Hernandez-Andrade⁠, E.; Hassan, S.S.; Romero, R.; van den Heuvel, M.P.

    2018-01-01

    Advances in neuroimaging and network analyses have lead to discovery of highly connected regions, or hubs, in the connectional architecture of the human brain. Whether these hubs emerge as networks begin to form in utero, has yet to be examined. The current study addresses this question and aims to

  3. Brain activation during human male ejaculation

    NARCIS (Netherlands)

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

    2003-01-01

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

  4. Some novel approaches in modelling and image reconstruction for multi-frequency Electrical Impedance Tomography of the human brain

    Science.gov (United States)

    Horesh, Lior

    Electrical Impedance Tomography (EIT) is a recently developed imaging technique. Small insensible currents are injected into the body using electrodes. Measured voltages are used for reconstruction of images of the internal dielectric properties of the body. This imaging technique is portable, safe, rapid, inexpensive and has the potential to provide a new method for imaging in remote or acute situations, where other large scanners, such as MRI, are either impractical or unavailable. It has been in use in clinical research for about two decades but has not yet been adopted into routine clinical practice. One potentially powerful clinical application lies in its use for imaging acute stroke, where it could be used to distinguish haemorrhage from infarction. Hitherto, image reconstruction has mainly been for the more tractable case of changes in impedance over time. For acute stroke, it is best operated in multiple frequency mode, where data is collected at multiple frequencies and images can be recovered with higher fidelity. Whereas the eventual idea appears to be good, there are several important issues which affect the likelihood of its success in producing clinically reliable images. These include limitations in accuracy of finite element modelling, image reconstruction, and accuracy of recorded voltage data due to noise and confounding factors. The purpose of this work was to address these issues in the hope that, at the end, a clinical study of EIT in acute stroke would have a much greater chance of success. In order to address the feasibility of this application, a comprehensive literature review regarding the dielectric properties of human head tissues in normal and pathological states was conducted in this thesis. Novel generic tools were developed in order to enable modelling and non-linear image reconstruction of large-scale problems, such as those arising from the head EIT problem.

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

    Science.gov (United States)

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

    2017-04-01

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

  6. Human brain glycogen content and metabolism: implications on its role in brain energy metabolism.

    Science.gov (United States)

    Oz, Gülin; Seaquist, Elizabeth R; Kumar, Anjali; Criego, Amy B; Benedict, Luke E; Rao, Jyothi P; Henry, Pierre-Gilles; Van De Moortele, Pierre-Francois; Gruetter, Rolf

    2007-03-01

    The adult brain relies on glucose for its energy needs and stores it in the form of glycogen, primarily in astrocytes. Animal and culture studies indicate that brain glycogen may support neuronal function when the glucose supply from the blood is inadequate and/or during neuronal activation. However, the concentration of glycogen and rates of its metabolism in the human brain are unknown. We used in vivo localized 13C-NMR spectroscopy to measure glycogen content and turnover in the human brain. Nine healthy volunteers received intravenous infusions of [1-(13)C]glucose for durations ranging from 6 to 50 h, and brain glycogen labeling and washout were measured in the occipital lobe for up to 84 h. The labeling kinetics suggest that turnover is the main mechanism of label incorporation into brain glycogen. Upon fitting a model of glycogen metabolism to the time courses of newly synthesized glycogen, human brain glycogen content was estimated at approximately 3.5 micromol/g, i.e., three- to fourfold higher than free glucose at euglycemia. Turnover of bulk brain glycogen occurred at a rate of 0.16 micromol.g-1.h-1, implying that complete turnover requires 3-5 days. Twenty minutes of visual stimulation (n=5) did not result in detectable glycogen utilization in the visual cortex, as judged from similar [13C]glycogen levels before and after stimulation. We conclude that the brain stores a substantial amount of glycogen relative to free glucose and metabolizes this store very slowly under normal physiology.

  7. Imaging visual function of the human brain

    International Nuclear Information System (INIS)

    Marg, E.

    1988-01-01

    Imaging of human brain structure and activity with particular reference to visual function is reviewed along with methods of obtaining the data including computed tomographic (CT) scan, magnetic resonance imaging (MRI), magnetic resonance spectroscopy (MRS), and positron emission tomography (PET). The literature is reviewed and the potential for a new understanding of brain visual function is discussed. PET is reviewed from basic physical principles to the most recent visual brain findings with oxygen-15. It is shown that there is a potential for submillimeter localization of visual functions with sequentially different visual stimuli designed for the temporal separation of the responses. Single photon emission computed tomography (SPECT), a less expensive substitute for PET, is also discussed. MRS is covered from basic physical principles to the current state of the art of in vivo biochemical analysis. Future possible clinical applications are discussed. Improved understanding of the functional neural organization of vision and brain will open a window to maps and circuits of human brain function.119 references

  8. [Evolution of human brain and intelligence].

    Science.gov (United States)

    Lakatos, László; Janka, Zoltán

    2008-07-30

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

  9. CSF transthyretin neuroprotection in a mouse model of brain ischemia

    DEFF Research Database (Denmark)

    Santos, Sofia Duque; Lambertsen, Kate Lykke; Clausen, Bettina Hjelm

    2010-01-01

    Brain injury caused by ischemia is a major cause of human mortality and physical/cognitive disability worldwide. Experimentally, brain ischemia can be induced surgically by permanent middle cerebral artery occlusion. Using this model, we studied the influence of transthyretin in ischemic stroke. ...

  10. Human Adipose-Derived Stem Cell (ASC) Treatment Modulates Cellular Protection in Both in Vitro and in Vivo Traumatic Brain Injury Models.

    Science.gov (United States)

    Kappy, Nikolas S; Chang, Shaohua; Harris, William M; Plastini, Michael; Ortiz, Telisha; Zhang, Ping; Hazelton, Joshua P; Carpenter, Jeffrey P; Brown, Spencer A

    2017-12-14

    Traumatic brain injury (TBI) is a common cause of morbidity and mortality in the civilian population. The purpose of this study is to examine the effect(s) of ASC treatment on cellular and functional recovery in TBI via both in vitro and in vivo methods. Cultured neuroblastoma cells, SH-SY5Y, were scratched to mimic TBI in an in vitro model. The effect of ASC conditioned medium on cell death, mitochondrial function, and expression of inflammatory cytokines (TNF-α, IL-1β and IL-6) as well as apoptosis marker FAS was measured. In our in vivo model, Sprague-Dawley rats underwent TBI via a frontal, closed head injury model. Animals randomly received either intravenous human derived ASCs or intravenous saline within 3 hours of injury, and were compared to a Sham group. Functional recovery was evaluated via accelerating Rotarod method. On post-TBI day 3, brain tissue was harvested and assessed for cellular damage via ELISA assay for TNF-α, as well as immunohistochemical staining for β-APP. Our in vitro data show that ASC treatment imparted reduced cell death (Ratio to control: 1.21±0.066 vs. 1.01±0.056, p=0.017), increased cell viability (Ratio to control: 0.86±0.009 vs. 1.09±0.01, p = 0.0001), increased mitochondrial function (Percentage of Control: 78±6% vs. 68±3%), and significantly decreased levels of inflammatory cytokine IL-1β. In our in vivo study, compared to TBI alone, ASC treated animals showed no difference in functional recovery, lower levels of expressed TNF-α (Ratio to total protein: 0.47±0.01 vs. 0.67±0.04; pprotection and recovery in neural cells following TBI. Level IIStudy Type: Therapeutic/Care Management.

  11. Hubs in the human fetal brain network.

    Science.gov (United States)

    van den Heuvel, Marion I; Turk, Elise; Manning, Janessa H; Hect, Jasmine; Hernandez-Andrade, Edgar; Hassan, Sonia S; Romero, Roberto; van den Heuvel, Martijn P; Thomason, Moriah E

    2018-02-06

    Advances in neuroimaging and network analyses have lead to discovery of highly connected regions, or hubs, in the connectional architecture of the human brain. Whether these hubs emerge in utero, has yet to be examined. The current study addresses this question and aims to determine the location of neural hubs in human fetuses. Fetal resting-state fMRI data (N = 105) was used to construct connectivity matrices for 197 discrete brain regions. We discovered that within the connectional functional organization of the human fetal brain key hubs are emerging. Consistent with prior reports in infants, visual and motor regions were identified as emerging hub areas, specifically in cerebellar areas. We also found evidence for network hubs in association cortex, including areas remarkably close to the adult fusiform facial and Wernicke areas. Functional significance of hub structure was confirmed by computationally deleting hub versus random nodes and observing that global efficiency decreased significantly more when hubs were removed (p hubs may be important for facilitating network communication, they may also form potential points of vulnerability in fetal brain development. Copyright © 2018. Published by Elsevier Ltd.

  12. Quantifying anisotropy and fiber orientation in human brain histological sections

    Directory of Open Access Journals (Sweden)

    Matthew D Budde

    2013-02-01

    Full Text Available Diffusion weighted imaging (DWI has provided unparalleled insight into the microscopic structure and organization of the central nervous system. Diffusion tensor imaging (DTI and other models of the diffusion MRI signal extract microstructural properties of tissues with relevance to the normal and injured brain. Despite the prevalence of such techniques and applications, accurate and large-scale validation has proven difficult, particularly in the human brain. In this report, human brain sections obtained from a digital public brain bank were employed to quantify anisotropy and fiber orientation using structure tensor analysis. The derived maps depict the intricate complexity of white matter fibers at a resolution not attainable with current DWI experiments. Moreover, the effects of multiple fiber bundles (i.e. crossing fibers and intravoxel fiber dispersion were demonstrated. Examination of the cortex and hippocampal regions validated specific features of previous in vivo and ex vivo DTI studies of the human brain. Despite the limitation to two dimensions, the resulting images provide a unique depiction of white matter organization at resolutions currently unattainable with DWI. The method of analysis may be used to validate tissue properties derived from DTI and alternative models of the diffusion signal.

  13. [Learning and memory amelioration of transplantation of the neural stem cells modified with human brain-derived neurotrophic factor gene on Alzheimer disease model rat].

    Science.gov (United States)

    Zhao, Zhiying; Hu, Haitao; Feng, Gaifeng

    2005-05-01

    To investigate the memory amelioration of the Alzheimer disease (AD) model rat after being transplanted the single neural stem cells (NSC) and NSC modified with human brain-derived neurotrophic factor (hBDNF) gene. Forty SD rats were divided evenly into 4 groups randomly. The AD model rats were made by cutting unilaterally the fibria-fornix of male rats. Ten to twelve days after surgery, the genetically modified and unmodified NSC were implanted into the lateral cerebral ventricle of group III and group IV respectively. Two weeks after transplantation, the amelioration of memory impairment of the rats was detected by Morris water maze. The average escaping latency of the group III and group IV (41.84 +/- 21.76 s, 25.23 +/- 17.06 s respectively) was shorter than that of the group II (70.91 +/- 23.67 s) (P0.05). More lineal and oriented strategies were used in group IV. The behavioral amelioration of AD model rat was obtained by transplanting single NSC and hBDNF-gene-modified NSC. The effect of the NSC group modified with hBDNF gene is better than that of the group III.

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

    Science.gov (United States)

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

    2017-06-22

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

  15. Human emotion in the brain and the body: Why language matters. Comment on "The quartet theory of human emotions: An integrative and neurofunctional model" by S. Koelsch et al.

    Science.gov (United States)

    Herbert, Cornelia

    2015-06-01

    What is an Emotion? This question has fascinated scientific research since William James. Despite the fact that a consensus has been reached about the biological origin of emotions, uniquely human aspects of emotions are still poorly understood. One of these blind spots concerns the relationship between emotion and human language. Historically, many theories imply a duality between emotions on the one hand and cognitive functions such as language on the other hand. Especially for symbolic forms of written language and word processing, it has been assumed that semantic information would bear no relation to bodily, affective, or sensorimotor processing (for an overview see Ref. [1]). The Quartet Theory proposed by Koelsch and colleagues [2] could provide a solution to this problem. It offers a novel, integrative neurofunctional model of human emotions which considers language and emotion as closely related. Crucially, language - be it spoken or written - is assumed to "regulate, modulate, and partly initiate" activity in core affective brain systems in accord with physical needs and individual concerns [cf. page 34, line 995]. In this regard, the Quartet Theory combines assumptions from earlier bioinformational theories of emotions [3], contemporary theories of embodied cognition [4], and appraisal theories such as the Component Process Model [5] into one framework, thereby providing a holistic model for the neuroscientific investigation of human emotion processing at the interface of emotion and cognition, mind and body.

  16. Imaging Monoamine Oxidase in the Human Brain

    Energy Technology Data Exchange (ETDEWEB)

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

    1999-11-10

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

  17. Imaging Monoamine Oxidase in the Human Brain

    International Nuclear Information System (INIS)

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

    1999-01-01

    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

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

    Science.gov (United States)

    Diamant, Emanuel

    2008-08-15

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

  19. Modelling Brain Tissue using Magnetic Resonance Imaging

    DEFF Research Database (Denmark)

    Dyrby, Tim Bjørn

    2008-01-01

    Diffusion MRI, or diffusion weighted imaging (DWI), is a technique that measures the restricted diffusion of water molecules within brain tissue. Different reconstruction methods quantify water-diffusion anisotropy in the intra- and extra-cellular spaces of the neural environment. Fibre tracking...... in the first time period of the scanning session. Probabilistic tractography was validated against two invasive in vivo neuronal tracers that were used to derive a gold standard. A high spatial agreement between tractography and the gold standard was found, and some of the widely known limitations...... experiment. This includes the selection of independent anatomical data to be used to derive a gold standard, the selection of a gyrated animal model in place of the human brain, objective selection of the seed region to initiate, and a waypoint region to constrain the tractography results....

  20. Modeling of Brain Shift Phenomenon for Different Craniotomies and Solid Models

    Directory of Open Access Journals (Sweden)

    Alvaro Valencia

    2012-01-01

    Full Text Available This study investigates the effects of different solid models on predictions of brain shift for three craniotomies. We created a generic 3D brain model based on healthy human brain and modeled the brain parenchyma as single continuum and constrained by a practically rigid skull. We have used elastic model, hyperelastic 1st, 2nd, and 3rd Ogden models, and hyperelastic Mooney-Rivlin with 2- and 5-parameter models. A pressure on the brain surface at craniotomy region was applied to load the model. The models were solved with the finite elements package ANSYS. The predictions on stress and displacements were compared for three different craniotomies. The difference between the predictions of elastic solid model and a hyperelastic Ogden solid model of maximum brain displacement and maximum effective stress is relevant.

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

    Directory of Open Access Journals (Sweden)

    Ajay Singh

    2009-03-01

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

  2. Differences in Gaussian diffusion tensor imaging and non-Gaussian diffusion kurtosis imaging model-based estimates of diffusion tensor invariants in the human brain.

    Science.gov (United States)

    Lanzafame, S; Giannelli, M; Garaci, F; Floris, R; Duggento, A; Guerrisi, M; Toschi, N

    2016-05-01

    An increasing number of studies have aimed to compare diffusion tensor imaging (DTI)-related parameters [e.g., mean diffusivity (MD), fractional anisotropy (FA), radial diffusivity (RD), and axial diffusivity (AD)] to complementary new indexes [e.g., mean kurtosis (MK)/radial kurtosis (RK)/axial kurtosis (AK)] derived through diffusion kurtosis imaging (DKI) in terms of their discriminative potential about tissue disease-related microstructural alterations. Given that the DTI and DKI models provide conceptually and quantitatively different estimates of the diffusion tensor, which can also depend on fitting routine, the aim of this study was to investigate model- and algorithm-dependent differences in MD/FA/RD/AD and anisotropy mode (MO) estimates in diffusion-weighted imaging of human brain white matter. The authors employed (a) data collected from 33 healthy subjects (20-59 yr, F: 15, M: 18) within the Human Connectome Project (HCP) on a customized 3 T scanner, and (b) data from 34 healthy subjects (26-61 yr, F: 5, M: 29) acquired on a clinical 3 T scanner. The DTI model was fitted to b-value =0 and b-value =1000 s/mm(2) data while the DKI model was fitted to data comprising b-value =0, 1000 and 3000/2500 s/mm(2) [for dataset (a)/(b), respectively] through nonlinear and weighted linear least squares algorithms. In addition to MK/RK/AK maps, MD/FA/MO/RD/AD maps were estimated from both models and both algorithms. Using tract-based spatial statistics, the authors tested the null hypothesis of zero difference between the two MD/FA/MO/RD/AD estimates in brain white matter for both datasets and both algorithms. DKI-derived MD/FA/RD/AD and MO estimates were significantly higher and lower, respectively, than corresponding DTI-derived estimates. All voxelwise differences extended over most of the white matter skeleton. Fractional differences between the two estimates [(DKI - DTI)/DTI] of most invariants were seen to vary with the invariant value itself as well as with MK

  3. Segmentation and Visualisation of Human Brain Structures

    Energy Technology Data Exchange (ETDEWEB)

    Hult, Roger

    2003-10-01

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

  4. Human astrocytes: structure and functions in the healthy brain.

    Science.gov (United States)

    Vasile, Flora; Dossi, Elena; Rouach, Nathalie

    2017-07-01

    Data collected on astrocytes' physiology in the rodent have placed them as key regulators of synaptic, neuronal, network, and cognitive functions. While these findings proved highly valuable for our awareness and appreciation of non-neuronal cell significance in brain physiology, early structural and phylogenic investigations of human astrocytes hinted at potentially different astrocytic properties. This idea sparked interest to replicate rodent-based studies on human samples, which have revealed an analogous but enhanced involvement of astrocytes in neuronal function of the human brain. Such evidence pointed to a central role of human astrocytes in sustaining more complex information processing. Here, we review the current state of our knowledge of human astrocytes regarding their structure, gene profile, and functions, highlighting the differences with rodent astrocytes. This recent insight is essential for assessment of the relevance of findings using animal models and for comprehending the functional significance of species-specific properties of astrocytes. Moreover, since dysfunctional astrocytes have been described in many brain disorders, a more thorough understanding of human-specific astrocytic properties is crucial for better-adapted translational applications.

  5. Non-negative Tensor Factorization with missing data for the modeling of gene expressions in the Human Brain

    DEFF Research Database (Denmark)

    Nielsen, Søren Føns Vind; Mørup, Morten

    2014-01-01

    of the component matrices. We examine three gene expression prediction scenarios based on data missing at random, whole genes missing and whole areas missing within a subject. We find that the column-wise updating approach also known as HALS performs the most efficient when fitting the model. We further observe...

  6. Inferring human intentions from the brain data

    DEFF Research Database (Denmark)

    Stanek, Konrad

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

  7. Mathematical logic in the human brain: semantics.

    Science.gov (United States)

    Friedrich, Roland M; Friederici, Angela D

    2013-01-01

    As a higher cognitive function in humans, mathematics is supported by parietal and prefrontal brain regions. Here, we give an integrative account of the role of the different brain systems in processing the semantics of mathematical logic from the perspective of macroscopic polysynaptic networks. By comparing algebraic and arithmetic expressions of identical underlying structure, we show how the different subparts of a fronto-parietal network are modulated by the semantic domain, over which the mathematical formulae are interpreted. Within this network, the prefrontal cortex represents a system that hosts three major components, namely, control, arithmetic-logic, and short-term memory. This prefrontal system operates on data fed to it by two other systems: a premotor-parietal top-down system that updates and transforms (external) data into an internal format, and a hippocampal bottom-up system that either detects novel information or serves as an access device to memory for previously acquired knowledge.

  8. Human brain lesion-deficit inference remapped.

    Science.gov (United States)

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

    2014-09-01

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

  9. Positive selection on gene expression in the human brain

    DEFF Research Database (Denmark)

    Khaitovich, Philipp; Tang, Kun; Franz, Henriette

    2006-01-01

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

  10. Scalability of human models

    NARCIS (Netherlands)

    Rodarius, C.; Rooij, L. van; Lange, R. de

    2007-01-01

    The objective of this work was to create a scalable human occupant model that allows adaptation of human models with respect to size, weight and several mechanical parameters. Therefore, for the first time two scalable facet human models were developed in MADYMO. First, a scalable human male was

  11. Mobile phone types and SAR characteristics of the human brain

    Science.gov (United States)

    Lee, Ae-Kyoung; Hong, Seon-Eui; Kwon, Jong-Hwa; Choi, Hyung-Do; Cardis, Elisabeth

    2017-04-01

    Mobile phones differ in terms of their operating frequency, outer shape, and form and location of the antennae, all of which affect the spatial distributions of their electromagnetic field and the level of electromagnetic absorption in the human head or brain. For this paper, the specific absorption rate (SAR) was calculated for four anatomical head models at different ages using 11 numerical phone models of different shapes and antenna configurations. The 11 models represent phone types accounting for around 86% of the approximately 1400 commercial phone models released into the Korean market since 2002. Seven of the phone models selected have an internal dual-band antenna, and the remaining four possess an external antenna. Each model was intended to generate an average absorption level equivalent to that of the same type of commercial phone model operating at the maximum available output power. The 1 g peak spatial SAR and ipsilateral and contralateral brain-averaged SARs were reported for all 11 phone models. The effects of the phone type, phone position, operating frequency, and age of head models on the brain SAR were comprehensively determined.

  12. Mobile phone types and SAR characteristics of the human brain.

    Science.gov (United States)

    Lee, Ae-Kyoung; Hong, Seon-Eui; Kwon, Jong-Hwa; Choi, Hyung-Do; Cardis, Elisabeth

    2017-04-07

    Mobile phones differ in terms of their operating frequency, outer shape, and form and location of the antennae, all of which affect the spatial distributions of their electromagnetic field and the level of electromagnetic absorption in the human head or brain. For this paper, the specific absorption rate (SAR) was calculated for four anatomical head models at different ages using 11 numerical phone models of different shapes and antenna configurations. The 11 models represent phone types accounting for around 86% of the approximately 1400 commercial phone models released into the Korean market since 2002. Seven of the phone models selected have an internal dual-band antenna, and the remaining four possess an external antenna. Each model was intended to generate an average absorption level equivalent to that of the same type of commercial phone model operating at the maximum available output power. The 1 g peak spatial SAR and ipsilateral and contralateral brain-averaged SARs were reported for all 11 phone models. The effects of the phone type, phone position, operating frequency, and age of head models on the brain SAR were comprehensively determined.

  13. Evolvability of Amyloidogenic Proteins in Human Brain

    Science.gov (United States)

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

    2018-01-01

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

  14. Loss of Brain Aerobic Glycolysis in Normal Human Aging.

    Science.gov (United States)

    Goyal, Manu S; Vlassenko, Andrei G; Blazey, Tyler M; Su, Yi; Couture, Lars E; Durbin, Tony J; Bateman, Randall J; Benzinger, Tammie L-S; Morris, John C; Raichle, Marcus E

    2017-08-01

    The normal aging human brain experiences global decreases in metabolism, but whether this affects the topography of brain metabolism is unknown. Here we describe PET-based measurements of brain glucose uptake, oxygen utilization, and blood flow in cognitively normal adults from 20 to 82 years of age. Age-related decreases in brain glucose uptake exceed that of oxygen use, resulting in loss of brain aerobic glycolysis (AG). Whereas the topographies of total brain glucose uptake, oxygen utilization, and blood flow remain largely stable with age, brain AG topography changes significantly. Brain regions with high AG in young adults show the greatest change, as do regions with prolonged developmental transcriptional features (i.e., neoteny). The normal aging human brain thus undergoes characteristic metabolic changes, largely driven by global loss and topographic changes in brain AG. Copyright © 2017 Elsevier Inc. All rights reserved.

  15. Network Dynamics with BrainX3: A Large-Scale Simulation of the Human Brain Network with Real-Time Interaction

    OpenAIRE

    Xerxes D. Arsiwalla; Riccardo eZucca; Alberto eBetella; Enrique eMartinez; David eDalmazzo; Pedro eOmedas; Gustavo eDeco; Gustavo eDeco; Paul F.M.J. Verschure; Paul F.M.J. Verschure

    2015-01-01

    BrainX3 is a large-scale simulation of human brain activity with real-time interaction, rendered in 3D in a virtual reality environment, which combines computational power with human intuition for the exploration and analysis of complex dynamical networks. We ground this simulation on structural connectivity obtained from diffusion spectrum imaging data and model it on neuronal population dynamics. Users can interact with BrainX3 in real-time by perturbing brain regions with transient stimula...

  16. Network dynamics with BrainX3: a large-scale simulation of the human brain network with real-time interaction

    OpenAIRE

    Arsiwalla, Xerxes D.; Zucca, Riccardo; Betella, Alberto; Martínez, Enrique, 1961-; Dalmazzo, David; Omedas, Pedro; Deco, Gustavo; Verschure, Paul F. M. J.

    2015-01-01

    BrainX3 is a large-scale simulation of human brain activity with real-time interaction, rendered in 3D in a virtual reality environment, which combines computational power with human intuition for the exploration and analysis of complex dynamical networks. We ground this simulation on structural connectivity obtained from diffusion spectrum imaging data and model it on neuronal population dynamics. Users can interact with BrainX3 in real-time by perturbing brain regions with transient stimula...

  17. Red and NIR light dosimetry in the human deep brain.

    Science.gov (United States)

    Pitzschke, A; Lovisa, B; Seydoux, O; Zellweger, M; Pfleiderer, M; Tardy, Y; Wagnières, G

    2015-04-07

    Photobiomodulation (PBM) appears promising to treat the hallmarks of Parkinson's Disease (PD) in cellular or animal models. We measured light propagation in different areas of PD-relevant deep brain tissue during transcranial, transsphenoidal illumination (at 671 and 808 nm) of a cadaver head and modeled optical parameters of human brain tissue using Monte-Carlo simulations. Gray matter, white matter, cerebrospinal fluid, ventricles, thalamus, pons, cerebellum and skull bone were processed into a mesh of the skull (158 × 201 × 211 voxels; voxel side length: 1 mm). Optical parameters were optimized from simulated and measured fluence rate distributions. The estimated μeff for the different tissues was in all cases larger at 671 than at 808 nm, making latter a better choice for light delivery in the deep brain. Absolute values were comparable to those found in the literature or slightly smaller. The effective attenuation in the ventricles was considerably larger than literature values. Optimization yields a new set of optical parameters better reproducing the experimental data. A combination of PBM via the sphenoid sinus and oral cavity could be beneficial. A 20-fold higher efficiency of light delivery to the deep brain was achieved with ventricular instead of transcranial illumination. Our study demonstrates that it is possible to illuminate deep brain tissues transcranially, transsphenoidally and via different application routes. This opens therapeutic options for sufferers of PD or other cerebral diseases necessitating light therapy.

  18. Development of Open Brain Simulator for Human Biomechatronics

    Science.gov (United States)

    Otake, Mihoko; Takagi, Toshihisa; Asama, Hajime

    Modeling and simulation based on mechanisms is important in order to design and control mechatronic systems. In particular, in-depth understanding and realistic modeling of biological systems is indispensable for biomechatronics. This paper presents open brain simulator, which estimates the neural state of human through external measurement for the purpose of improving motor and social skills. Macroscopic anatomical nervous systems model was built which can be connected to the musculoskeletal model. Microscopic anatomical and physiological neural models were interfaced to the macroscopic model. Neural activities of somatosensory area and Purkinje cell were calculated from motion capture data. The simulator provides technical infrastructure for human biomechatronics, which is promising for the novel diagnosis of neurological disorders and their treatments through medication and movement therapy, and for motor learning support system supporting acquisition of motor skill considering neural mechanism.

  19. Kinetic modeling of [18F]VAT, a novel radioligand for positron emission tomography imaging vesicular acetylcholine transporter in non-human primate brain.

    Science.gov (United States)

    Jin, Hongjun; Yue, Xuyi; Liu, Hui; Han, Junbin; Flores, Hubert; Su, Yi; Parsons, Stanley M; Perlmutter, Joel S; Tu, Zhude

    2018-01-06

    Molecular imaging of vesicular acetylcholine transporter (VAChT) in the brain provides an important cholinergic biomarker for the pathophysiology and treatment of dementias including Alzheimer's disease. In this study, kinetics modeling methods were applied and compared for quantifying regional brain uptake of the VAChT-specific positron emission tomography radiotracer, ((-)-(1-(-8-(2-fluoroethoxy)-3-hydroxy-1,2,3,4-tetrahydronaphthalen-2-yl)piperidin-4-yl)(4-fluorophenyl)-methanone) ([ 18 F]VAT) in macaques. Total volume distribution (V T ) estimates were compared for one-tissue compartment model (1TCM), two-tissue compartment model (2TCM), Logan graphic analysis (LoganAIF) and multiple linear analysis (MA1) with arterial blood input function using data from three macaques. Using the cerebellum-hemispheres as the reference region with data from seven macaques, three additional models were compared: reference tissue model (RTM), simplified RTM (SRTM), and Logan graphic analysis (LoganREF). Model selection criterion indicated that a) 2TCM and SRTM were the most appropriate kinetics models for [ 18 F]VAT; and b) SRTM was strongly correlated with 2TCM (Pearson's coefficients r > 0.93, p VAT has good reproducibility and reliability (TRV  0.72). These studies demonstrate [ 18 F]VAT is a promising VAChT positron emission tomography tracer for quantitative assessment of VAChT levels in the brain of living subjects. © 2018 International Society for Neurochemistry.

  20. Biomechanical Modeling of the Human Head

    Science.gov (United States)

    2017-10-03

    Experimental Animal Models for Studies on the Mechanisms of Blast- Induced Neurotrauma,” Frontiers in Neurology 3, 30 (2012). 13. R. A. Bauman, G. Ling...modeling, of both humans and animals , has gained momentum for the investigation of traumatic brain injury. These models require both accurate geometric...between model predictions and experimental data. This report details model calibration for all materials identified in models of a human head and

  1. Predicting human brain activity associated with the meanings of nouns.

    Science.gov (United States)

    Mitchell, Tom M; Shinkareva, Svetlana V; Carlson, Andrew; Chang, Kai-Min; Malave, Vicente L; Mason, Robert A; Just, Marcel Adam

    2008-05-30

    The question of how the human brain represents conceptual knowledge has been debated in many scientific fields. Brain imaging studies have shown that different spatial patterns of neural activation are associated with thinking about different semantic categories of pictures and words (for example, tools, buildings, and animals). We present a computational model that predicts the functional magnetic resonance imaging (fMRI) neural activation associated with words for which fMRI data are not yet available. This model is trained with a combination of data from a trillion-word text corpus and observed fMRI data associated with viewing several dozen concrete nouns. Once trained, the model predicts fMRI activation for thousands of other concrete nouns in the text corpus, with highly significant accuracies over the 60 nouns for which we currently have fMRI data.

  2. Combination therapy of human umbilical cord blood cells and granulocyte colony stimulating factor reduces histopathological and motor impairments in an experimental model of chronic traumatic brain injury.

    Directory of Open Access Journals (Sweden)

    Sandra A Acosta

    Full Text Available Traumatic brain injury (TBI is associated with neuro-inflammation, debilitating sensory-motor deficits, and learning and memory impairments. Cell-based therapies are currently being investigated in treating neurotrauma due to their ability to secrete neurotrophic factors and anti-inflammatory cytokines that can regulate the hostile milieu associated with chronic neuroinflammation found in TBI. In tandem, the stimulation and mobilization of endogenous stem/progenitor cells from the bone marrow through granulocyte colony stimulating factor (G-CSF poses as an attractive therapeutic intervention for chronic TBI. Here, we tested the potential of a combined therapy of human umbilical cord blood cells (hUCB and G-CSF at the acute stage of TBI to counteract the progressive secondary effects of chronic TBI using the controlled cortical impact model. Four different groups of adult Sprague Dawley rats were treated with saline alone, G-CSF+saline, hUCB+saline or hUCB+G-CSF, 7-days post CCI moderate TBI. Eight weeks after TBI, brains were harvested to analyze hippocampal cell loss, neuroinflammatory response, and neurogenesis by using immunohistochemical techniques. Results revealed that the rats exposed to TBI treated with saline exhibited widespread neuroinflammation, impaired endogenous neurogenesis in DG and SVZ, and severe hippocampal cell loss. hUCB monotherapy suppressed neuroinflammation, nearly normalized the neurogenesis, and reduced hippocampal cell loss compared to saline alone. G-CSF monotherapy produced partial and short-lived benefits characterized by low levels of neuroinflammation in striatum, DG, SVZ, and corpus callosum and fornix, a modest neurogenesis, and a moderate reduction of hippocampal cells loss. On the other hand, combined therapy of hUCB+G-CSF displayed synergistic effects that robustly dampened neuroinflammation, while enhancing endogenous neurogenesis and reducing hippocampal cell loss. Vigorous and long-lasting recovery of

  3. Hierarchical modularity in human brain functional networks

    Directory of Open Access Journals (Sweden)

    David Meunier

    2009-10-01

    Full Text Available The idea that complex systems have a hierarchical modular organization originates in the early 1960s and has recently attracted fresh support from quantitative studies of large scale, real-life networks. Here we investigate the hierarchical modular (or “modules-within-modules” decomposition of human brain functional networks, measured using functional magnetic resonance imaging (fMRI in 18 healthy volunteers under no-task or resting conditions. We used a customized template to extract networks with more than 1800 regional nodes, and we applied a fast algorithm to identify nested modular structure at several hierarchical levels. We used mutual information, 0 < I < 1, to estimate the similarity of community structure of networks in different subjects, and to identify the individual network that is most representative of the group. Results show that human brain functional networks have a hierarchical modular organization with a fair degree of similarity between subjects, I=0.63. The largest 5 modules at the highest level of the hierarchy were medial occipital, lateral occipital, central, parieto-frontal and fronto-temporal systems; occipital modules demonstrated less sub-modular organization than modules comprising regions of multimodal association cortex. Connector nodes and hubs, with a key role in inter-modular connectivity, were also concentrated in association cortical areas. We conclude that methods are available for hierarchical modular decomposition of large numbers of high resolution brain functional networks using computationally expedient algorithms. This could enable future investigations of Simon's original hypothesis that hierarchy or near-decomposability of physical symbol systems is a critical design feature for their fast adaptivity to changing environmental conditions.

  4. Comparative analysis of the macroscale structural connectivity in the macaque and human brain.

    Directory of Open Access Journals (Sweden)

    Alexandros Goulas

    2014-03-01

    Full Text Available The macaque brain serves as a model for the human brain, but its suitability is challenged by unique human features, including connectivity reconfigurations, which emerged during primate evolution. We perform a quantitative comparative analysis of the whole brain macroscale structural connectivity of the two species. Our findings suggest that the human and macaque brain as a whole are similarly wired. A region-wise analysis reveals many interspecies similarities of connectivity patterns, but also lack thereof, primarily involving cingulate regions. We unravel a common structural backbone in both species involving a highly overlapping set of regions. This structural backbone, important for mediating information across the brain, seems to constitute a feature of the primate brain persevering evolution. Our findings illustrate novel evolutionary aspects at the macroscale connectivity level and offer a quantitative translational bridge between macaque and human research.

  5. Sex differences in the structural connectome of the human brain.

    Science.gov (United States)

    Ingalhalikar, Madhura; Smith, Alex; Parker, Drew; Satterthwaite, Theodore D; Elliott, Mark A; Ruparel, Kosha; Hakonarson, Hakon; Gur, Raquel E; Gur, Ruben C; Verma, Ragini

    2014-01-14

    Sex differences in human behavior show adaptive complementarity: Males have better motor and spatial abilities, whereas females have superior memory and social cognition skills. Studies also show sex differences in human brains but do not explain this complementarity. In this work, we modeled the structural connectome using diffusion tensor imaging in a sample of 949 youths (aged 8-22 y, 428 males and 521 females) and discovered unique sex differences in brain connectivity during the course of development. Connection-wise statistical analysis, as well as analysis of regional and global network measures, presented a comprehensive description of network characteristics. In all supratentorial regions, males had greater within-hemispheric connectivity, as well as enhanced modularity and transitivity, whereas between-hemispheric connectivity and cross-module participation predominated in females. However, this effect was reversed in the cerebellar connections. Analysis of these changes developmentally demonstrated differences in trajectory between males and females mainly in adolescence and in adulthood. Overall, the results suggest that male brains are structured to facilitate connectivity between perception and coordinated action, whereas female brains are designed to facilitate communication between analytical and intuitive processing modes.

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

    Science.gov (United States)

    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.

  7. Fundamental Dynamical Modes Underlying Human Brain Synchronization

    Directory of Open Access Journals (Sweden)

    Catalina Alvarado-Rojas

    2012-01-01

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

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

    Science.gov (United States)

    Rilling, James K

    2014-01-01

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

  9. A Bayesian Model of Category-Specific Emotional Brain Responses

    Science.gov (United States)

    Wager, Tor D.; Kang, Jian; Johnson, Timothy D.; Nichols, Thomas E.; Satpute, Ajay B.; Barrett, Lisa Feldman

    2015-01-01

    Understanding emotion is critical for a science of healthy and disordered brain function, but the neurophysiological basis of emotional experience is still poorly understood. We analyzed human brain activity patterns from 148 studies of emotion categories (2159 total participants) using a novel hierarchical Bayesian model. The model allowed us to classify which of five categories—fear, anger, disgust, sadness, or happiness—is engaged by a study with 66% accuracy (43-86% across categories). Analyses of the activity patterns encoded in the model revealed that each emotion category is associated with unique, prototypical patterns of activity across multiple brain systems including the cortex, thalamus, amygdala, and other structures. The results indicate that emotion categories are not contained within any one region or system, but are represented as configurations across multiple brain networks. The model provides a precise summary of the prototypical patterns for each emotion category, and demonstrates that a sufficient characterization of emotion categories relies on (a) differential patterns of involvement in neocortical systems that differ between humans and other species, and (b) distinctive patterns of cortical-subcortical interactions. Thus, these findings are incompatible with several contemporary theories of emotion, including those that emphasize emotion-dedicated brain systems and those that propose emotion is localized primarily in subcortical activity. They are consistent with componential and constructionist views, which propose that emotions are differentiated by a combination of perceptual, mnemonic, prospective, and motivational elements. Such brain-based models of emotion provide a foundation for new translational and clinical approaches. PMID:25853490

  10. A Dirichlet process mixture model for brain MRI tissue classification.

    Science.gov (United States)

    Ferreira da Silva, Adelino R

    2007-04-01

    Accurate classification of magnetic resonance images according to tissue type or region of interest has become a critical requirement in diagnosis, treatment planning, and cognitive neuroscience. Several authors have shown that finite mixture models give excellent results in the automated segmentation of MR images of the human normal brain. However, performance and robustness of finite mixture models deteriorate when the models have to deal with a variety of anatomical structures. In this paper, we propose a nonparametric Bayesian model for tissue classification of MR images of the brain. The model, known as Dirichlet process mixture model, uses Dirichlet process priors to overcome the limitations of current parametric finite mixture models. To validate the accuracy and robustness of our method we present the results of experiments carried out on simulated MR brain scans, as well as on real MR image data. The results are compared with similar results from other well-known MRI segmentation methods.

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

    Directory of Open Access Journals (Sweden)

    Suzana Herculano-Houzel

    2009-11-01

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

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

    Science.gov (United States)

    Herculano-Houzel, Suzana

    2009-01-01

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

  13. Memory-related brain lateralisation in birds and humans.

    Science.gov (United States)

    Moorman, Sanne; Nicol, Alister U

    2015-03-01

    Visual imprinting in chicks and song learning in songbirds are prominent model systems for the study of the neural mechanisms of memory. In both systems, neural lateralisation has been found to be involved in memory formation. Although many processes in the human brain are lateralised--spatial memory and musical processing involves mostly right hemisphere dominance, whilst language is mostly left hemisphere dominant--it is unclear what the function of lateralisation is. It might enhance brain capacity, make processing more efficient, or prevent occurrence of conflicting signals. In both avian paradigms we find memory-related lateralisation. We will discuss avian lateralisation findings and propose that birds provide a strong model for studying neural mechanisms of memory-related lateralisation. Copyright © 2014. Published by Elsevier Ltd.

  14. Gene Expression Changes in Long-Term In Vitro Human Blood-Brain Barrier Models and Their Dependence on a Transwell Scaffold Material

    Directory of Open Access Journals (Sweden)

    Joel D. Gaston

    2017-01-01

    Full Text Available Disruption of the blood-brain barrier (BBB is the hallmark of many neurovascular disorders, making it a critically important focus for therapeutic options. However, testing the effects of either drugs or pathological agents is difficult due to the potentially damaging consequences of altering the normal brain microenvironment. Recently, in vitro coculture tissue models have been developed as an alternative to animal testing. Despite low cost, these platforms use synthetic scaffolds which prevent normal barrier architecture, cellular crosstalk, and tissue remodeling. We created a biodegradable electrospun gelatin mat “biopaper” (BP as a scaffold material for an endothelial/astrocyte coculture model allowing cell-cell contact and crosstalk. To compare the BP and traditional models, we investigated the expression of 27 genes involved in BBB permeability, cellular function, and endothelial junctions at different time points. Gene expression levels demonstrated higher expression of transcripts involved in endothelial junction formation, including TJP2 and CDH5, in the BP model. The traditional model had higher expression of genes associated with extracellular matrix-associated proteins, including SPARC and COL4A1. Overall, the results demonstrate that the BP coculture model is more representative of a healthy BBB state, though both models have advantages that may be useful in disease modeling.

  15. Listeriolysin O mediates cytotoxicity against human brain microvascular

    Science.gov (United States)

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

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

    Science.gov (United States)

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

    2013-01-01

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

  17. Frequency interactions in human epileptic brain.

    Science.gov (United States)

    Cotic, Marija; Zalay, Osbert; Valiante, Taufik; Carlen, Peter L; Bardakjian, Berj L

    2011-01-01

    We have used two algorithms, wavelet phase coherence (WPC) and modulation index (MI) analysis to study frequency interactions in the human epileptic brain. Quantitative analyses were performed on intracranial electroencephalographic (iEEG) segments from three patients with neocortical epilepsy. Interelectrode coherence was measured using WPC and intraelectrode frequency interactions were analyzed using MI. WPC was performed on electrode pairings and the temporal evolution of phase couplings in the following frequency ranges: 1-4 Hz, 4-8 Hz, 8-13 Hz, 13-30 Hz and 30-100 Hz was studied. WPC was strongest in the 1-4 Hz frequency range during both seizure and non-seizure activities; however, WPC values varied minimally between electrode pairings. The 13-30 Hz band showed the lowest WPC values during seizure activity. MI analysis yielded two prominent patterns of frequency-specific activity, during seizure and non-seizure activities, which were present across all patients.

  18. Calcium-activated potassium channels mediated blood-brain tumor barrier opening in a rat metastatic brain tumor model

    Directory of Open Access Journals (Sweden)

    Ong John M

    2007-03-01

    Full Text Available Abstract Background The blood-brain tumor barrier (BTB impedes the delivery of therapeutic agents to brain tumors. While adequate delivery of drugs occurs in systemic tumors, the BTB limits delivery of anti-tumor agents into brain metastases. Results In this study, we examined the function and regulation of calcium-activated potassium (KCa channels in a rat metastatic brain tumor model. We showed that intravenous infusion of NS1619, a KCa channel agonist, and bradykinin selectively enhanced BTB permeability in brain tumors, but not in normal brain. Iberiotoxin, a KCa channel antagonist, significantly attenuated NS1619-induced BTB permeability increase. We found KCa channels and bradykinin type 2 receptors (B2R expressed in cultured human metastatic brain tumor cells (CRL-5904, non-small cell lung cancer, metastasized to brain, human brain microvessel endothelial cells (HBMEC and human lung cancer brain metastasis tissues. Potentiometric assays demonstrated the activity of KCa channels in metastatic brain tumor cells and HBMEC. Furthermore, we detected higher expression of KCa channels in the metastatic brain tumor tissue and tumor capillary endothelia as compared to normal brain tissue. Co-culture of metastatic brain tumor cells and brain microvessel endothelial cells showed an upregulation of KCa channels, which may contribute to the overexpression of KCa channels in tumor microvessels and selectivity of BTB opening. Conclusion These findings suggest that KCa channels in metastatic brain tumors may serve as an effective target for biochemical modulation of BTB permeability to enhance selective delivery of chemotherapeutic drugs to metastatic brain tumors.

  19. Changes in cognitive state alter human functional brain networks

    Directory of Open Access Journals (Sweden)

    Malaak Nasser Moussa

    2011-08-01

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

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

    Directory of Open Access Journals (Sweden)

    ARTHUR eSANIOTIS

    2014-09-01

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

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

    Directory of Open Access Journals (Sweden)

    Søren Ventegodt

    2008-01-01

    Full Text Available The human brain is probably the most complicated single structure in the biological universe. The cerebral cortex that is traditionally connected with consciousness is extremely complex. The brain contains approximately 1,000,000 km of nerve fibers, indicating its enormous complexity and which makes it difficult for scientists to reveal the function of the brain. In this paper, we propose a new model for brain functions, i.e., information-guided self-organization of neural patterns, where information is provided from the abstract wholeness of the biophysical system of an organism (often called the true self, or the “soul””. We present a number of arguments in favor of this model that provide self-conscious control over the thought process or cognition. Our arguments arise from analyzing experimental data from different research fields: histology, anatomy, electroencephalography (EEG, cerebral blood flow, neuropsychology, evolutionary studies, and mathematics. We criticize the popular network theories as the consequence of a simplistic, mechanical interpretation of reality (philosophical materialism applied to the brain. We demonstrate how viewing brain functions as information-guided self-organization of neural patterns can explain the structure of conscious mentation; we seem to have a dual hierarchical representation in the cerebral cortex: one for sensation-perception and one for will-action. The model explains many of our unique mental abilities to think, memorize, associate, discriminate, and make abstractions. The presented model of the conscious brain also seems to be able to explain the function of the simpler brains, such as those of insects and hydra.

  2. From reverse transcription to human brain tumors

    Directory of Open Access Journals (Sweden)

    Dmitrenko V. V.

    2013-05-01

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

  3. In vivo imaging models of bone and brain metastases and pleural carcinomatosis with a novel human EML4-ALK lung cancer cell line.

    Science.gov (United States)

    Nanjo, Shigeki; Nakagawa, Takayuki; Takeuchi, Shinji; Kita, Kenji; Fukuda, Koji; Nakada, Mitsutoshi; Uehara, Hisanori; Nishihara, Hiroshi; Hara, Eiji; Uramoto, Hidetaka; Tanaka, Fumihiro; Yano, Seiji

    2015-03-01

    EML4-ALK lung cancer accounts for approximately 3-7% of non-small-cell lung cancer cases. To investigate the molecular mechanism underlying tumor progression and targeted drug sensitivity/resistance in EML4-ALK lung cancer, clinically relevant animal models are indispensable. In this study, we found that the lung adenocarcinoma cell line A925L expresses an EML4-ALK gene fusion (variant 5a, E2:A20) and is sensitive to the ALK inhibitors crizotinib and alectinib. We further established highly tumorigenic A925LPE3 cells, which also have the EML4-ALK gene fusion (variant 5a) and are sensitive to ALK inhibitors. By using A925LPE3 cells with luciferase gene transfection, we established in vivo imaging models for pleural carcinomatosis, bone metastasis, and brain metastasis, all of which are significant clinical concerns of advanced EML4-ALK lung cancer. Interestingly, crizotinib caused tumors to shrink in the pleural carcinomatosis model, but not in bone and brain metastasis models, whereas alectinib showed remarkable efficacy in all three models, indicative of the clinical efficacy of these ALK inhibitors. Our in vivo imaging models of multiple organ sites may provide useful resources to analyze further the pathogenesis of EML4-ALK lung cancer and its response and resistance to ALK inhibitors in various organ microenvironments. © 2015 The Authors. Cancer Science published by Wiley Publishing Asia Pty Ltd on behalf of Japanese Cancer Association.

  4. Evaluation of cat brain infarction model using microPET

    Energy Technology Data Exchange (ETDEWEB)

    Lee, Jong Jin; Lee, Dong Soo; Kim, Yun Hui; Hwang, Do Won; Kim, Jin Su; Chung, June Key; Lee, Myung Chul [College of Medicine, Seoul National Univ., Seoul (Korea, Republic of); Lim, Sang Moo [Korea Institite of Radiological and Medical Sciences, Seoul (Korea, Republic of)

    2004-12-01

    PET has some disadvantage in the imaging of small animal due to poor resolution. With the advent of microPET scanner, it is possible to image small animals. However, the image quality was not good enough as human image. Due to larger brain, cat brain imaging was superior to mouse or rat. In this study, we established the cat brain infarction model and evaluate it and its temporal change using microPET scanner. Two adult male cats were used. Anesthesia was done with xylazine and ketamine HCI. A burr hole was made at 1 cm right lateral to the bregma. Collagenase type IV 10 {mu}l was injected using 30 G needle for 5 minutes to establish the infarction model. {sup 18}F-FDG microPET (Concorde Microsystems Inc., Knoxville, TN) scans were performed 1, 11 and 32 days after the infarction. In addition, {sup 18}F-FDG PET scans were performed using human PET scanner (Gemini, Philips medical systems, CA, USA) 13 and 47 days after the infarction. Two cat brain infarction models were established. The glucose metabolism of an infarction lesion improved with time. An infarction lesion was also distinguishable in the human PET scan. We successfully established the cat brain infarction model and evaluated the infarcted lesion and its temporal change using {sup 18}F-FDG microPET scanner.

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

    Science.gov (United States)

    Cunnane, Stephen C; Crawford, Michael A

    2014-12-01

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

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

    Science.gov (United States)

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

    2015-01-01

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

  7. Neuronal connectivity, regional differentiation, and brain damage in humans.

    OpenAIRE

    Zaidel, Dahlia W.

    1999-01-01

    When circumscribed brain regions are damaged in humans, highly specific iimpairments in language, memory, problem solving, and cognition are observed. Neurosurgery such as "split brain" or hemispherectomy, for example has shown that encompassing regions, the left and right cerebral hemispheres each control human behavior in unique ways. Observations stretching over 100 years of patients with unilateral focal brain damage have revealed, withouth the theoretical benefits of "cognitive neurosci...

  8. Limitations of the hCMEC/D3 cell line as a model for Aβ clearance by the human blood-brain barrier.

    Science.gov (United States)

    Biemans, Elisanne A L M; Jäkel, Lieke; de Waal, Robert M W; Kuiperij, H Bea; Verbeek, Marcel M

    2017-07-01

    Alzheimer's disease and cerebral amyloid angiopathy are characterized by accumulation of amyloid-β (Aβ) at the cerebrovasculature due to decreased clearance at the blood-brain barrier (BBB). However, the exact mechanism of Aβ clearance across this barrier has not been fully elucidated. The hCMEC/D3 cell line has been characterized as a valid model for the BBB. In this study we evaluated the use of this model to study Aβ clearance across the BBB, with an emphasis on brain-to-blood directional permeability. Barrier integrity of hCMEC/D3 monolayers was confirmed for large molecules in both the apical to basolateral and the reverse direction. However, permeability for smaller molecules was substantially higher, especially in basolateral to apical direction, and barrier formation for Aβ was completely absent in this direction. In addition, hCMEC/D3 cells failed to develop a high TEER, possibly caused by incomplete formation of tight junctions. We conclude that the hCMEC/D3 model has several limitations to study the cerebral clearance of Aβ. Therefore, the model needs further characterization before this cell system can be generally applied as a model to study cerebral Aβ clearance. © 2016 The Authors Journal of Neuroscience Research Published by Wiley Periodicals, Inc. © 2016 The Authors Journal of Neuroscience Research Published by Wiley Periodicals, Inc.

  9. Evolutionary origins of human brain and spirituality.

    Science.gov (United States)

    Henneberg, Maciej; Saniotis, Arthur

    2009-12-01

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

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

    Science.gov (United States)

    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

  11. Resolving structural variability in network models and the brain.

    Directory of Open Access Journals (Sweden)

    Florian Klimm

    2014-03-01

    Full Text Available Large-scale white matter pathways crisscrossing the cortex create a complex pattern of connectivity that underlies human cognitive function. Generative mechanisms for this architecture have been difficult to identify in part because little is known in general about mechanistic drivers of structured networks. Here we contrast network properties derived from diffusion spectrum imaging data of the human brain with 13 synthetic network models chosen to probe the roles of physical network embedding and temporal network growth. We characterize both the empirical and synthetic networks using familiar graph metrics, but presented here in a more complete statistical form, as scatter plots and distributions, to reveal the full range of variability of each measure across scales in the network. We focus specifically on the degree distribution, degree assortativity, hierarchy, topological Rentian scaling, and topological fractal scaling--in addition to several summary statistics, including the mean clustering coefficient, the shortest path-length, and the network diameter. The models are investigated in a progressive, branching sequence, aimed at capturing different elements thought to be important in the brain, and range from simple random and regular networks, to models that incorporate specific growth rules and constraints. We find that synthetic models that constrain the network nodes to be physically embedded in anatomical brain regions tend to produce distributions that are most similar to the corresponding measurements for the brain. We also find that network models hardcoded to display one network property (e.g., assortativity do not in general simultaneously display a second (e.g., hierarchy. This relative independence of network properties suggests that multiple neurobiological mechanisms might be at play in the development of human brain network architecture. Together, the network models that we develop and employ provide a potentially useful

  12. An adaptive complex network model for brain functional networks.

    Directory of Open Access Journals (Sweden)

    Ignacio J Gomez Portillo

    Full Text Available Brain functional networks are graph representations of activity in the brain, where the vertices represent anatomical regions and the edges their functional connectivity. These networks present a robust small world topological structure, characterized by highly integrated modules connected sparsely by long range links. Recent studies showed that other topological properties such as the degree distribution and the presence (or absence of a hierarchical structure are not robust, and show different intriguing behaviors. In order to understand the basic ingredients necessary for the emergence of these complex network structures we present an adaptive complex network model for human brain functional networks. The microscopic units of the model are dynamical nodes that represent active regions of the brain, whose interaction gives rise to complex network structures. The links between the nodes are chosen following an adaptive algorithm that establishes connections between dynamical elements with similar internal states. We show that the model is able to describe topological characteristics of human brain networks obtained from functional magnetic resonance imaging studies. In particular, when the dynamical rules of the model allow for integrated processing over the entire network scale-free non-hierarchical networks with well defined communities emerge. On the other hand, when the dynamical rules restrict the information to a local neighborhood, communities cluster together into larger ones, giving rise to a hierarchical structure, with a truncated power law degree distribution.

  13. Bayesian Modelling of Functional Whole Brain Connectivity

    DEFF Research Database (Denmark)

    Røge, Rasmus

    This thesis deals with parcellation of whole-brain functional magnetic resonance imaging (fMRI) using Bayesian inference with mixture models tailored to the fMRI data. In the three included papers and manuscripts, we analyze two different approaches to modeling fMRI signal; either we accept...... the prevalent strategy of standardizing of fMRI time series and model data using directional statistics or we model the variability in the signal across the brain and across multiple subjects. In either case, we use Bayesian nonparametric modeling to automatically learn from the fMRI data the number...... of funcional units, i.e. parcels. We benchmark the proposed mixture models against state of the art methods of brain parcellation, both probabilistic and non-probabilistic. The time series of each voxel are most often standardized using z-scoring which projects the time series data onto a hypersphere...

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

    Directory of Open Access Journals (Sweden)

    Patric Hagmann

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

  15. Neuroglobin and Cytoglobin expression in the human brain

    DEFF Research Database (Denmark)

    Hundahl, Christian Ansgar; Kelsen, Jesper; Hay-Schmidt, Anders

    2013-01-01

    expressed and up-regulated following stroke in the human brain. The present study aimed at confirming our previous observations in rodents using two post-mortem human brains. The anatomical localization of Neuroglobin and Cytoglobin in the human brain is much like what has been described for the rodent...... and Cytoglobin in the cerebral cortex, while no expression in the cerebellar cortex was detectable. We provide a neuroanatomical indication for a different role of Neuroglobin and Cytoglobin in the human brain.......Neuroglobin and Cytoglobin are new members of the heme-globin family. Both globins are primarily expressed in neurons of the brain and retina. Neuroglobin and Cytoglobin have been suggested as novel therapeutic targets in various neurodegenerative diseases based on their oxygen binding and cell...

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

    Science.gov (United States)

    Hari, Riitta

    2017-06-07

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

  17. Melanoma Brain Metastasis: Mechanisms, Models, and Medicine

    Science.gov (United States)

    Kircher, David A.; Silvis, Mark R.; Cho, Joseph H.; Holmen, Sheri L.

    2016-01-01

    The development of brain metastases in patients with advanced stage melanoma is common, but the molecular mechanisms responsible for their development are poorly understood. Melanoma brain metastases cause significant morbidity and mortality and confer a poor prognosis; traditional therapies including whole brain radiation, stereotactic radiotherapy, or chemotherapy yield only modest increases in overall survival (OS) for these patients. While recently approved therapies have significantly improved OS in melanoma patients, only a small number of studies have investigated their efficacy in patients with brain metastases. Preliminary data suggest that some responses have been observed in intracranial lesions, which has sparked new clinical trials designed to evaluate the efficacy in melanoma patients with brain metastases. Simultaneously, recent advances in our understanding of the mechanisms of melanoma cell dissemination to the brain have revealed novel and potentially therapeutic targets. In this review, we provide an overview of newly discovered mechanisms of melanoma spread to the brain, discuss preclinical models that are being used to further our understanding of this deadly disease and provide an update of the current clinical trials for melanoma patients with brain metastases. PMID:27598148

  18. The progress of radiosensitive genes of human brain glioma

    International Nuclear Information System (INIS)

    Wang Xi; Liu Qiang

    2008-01-01

    Human gliomas are one of the most aggressive tumors in brain which grow infiltrativly. Surgery is the mainstay of treatment. But as the tumor could not be entirely cut off, it is easy to relapse. Radiotherapy plays an important role for patients with gliomas after surgery. The efficacy of radiotherapy is associated with radio sensitivity of human gliomas. This paper makes a summary of current situation and progress for radiosensitive genes of human brain gliomas. (authors)

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

    Science.gov (United States)

    Li, Guangye; Zhang, Dingguo

    2016-01-01

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

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

    Science.gov (United States)

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

    2015-12-15

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

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

    Science.gov (United States)

    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.

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

    Science.gov (United States)

    Cunnane, Stephen C

    2006-01-01

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

  3. Large Scale Computing for the Modelling of Whole Brain Connectivity

    DEFF Research Database (Denmark)

    Albers, Kristoffer Jon

    , which allows us to couple and explore different models and sampling procedures in runtime, still being applied to full-sized data. Using the implemented tools, we demonstrate that the models successfully can be applied for clustering whole-brain connectivity networks. Without being informed of spatial......The human brain constitutes an impressive network formed by the structural and functional connectivity patterns between billions of neurons. Modern functional and diffusion magnetic resonance imaging (fMRI and dMRI) provides unprecedented opportunities for exploring the functional and structural...... organization of the brain in continuously increasing resolution. From these images, networks of structural and functional connectivity can be constructed. Bayesian stochastic block modelling provides a prominent data-driven approach for uncovering the latent organization, by clustering the networks into groups...

  4. Alterations in the human brain in menopause

    NARCIS (Netherlands)

    Ishunina, T.A.; Swaab, D.F.

    2007-01-01

    In a series of studies we showed that menopause in women causes alterations not only in the neuronal expression of estrogen receptors (ER) alpha and beta, but also in local estrogen production in several brain areas and in the rate of neuronal metabolism. Although such changes are clearly brain

  5. Flow distributions and spatial correlations in human brain capillary networks

    Science.gov (United States)

    Lorthois, Sylvie; Peyrounette, Myriam; Larue, Anne; Le Borgne, Tanguy

    2015-11-01

    The vascular system of the human brain cortex is composed of a space filling mesh-like capillary network connected upstream and downstream to branched quasi-fractal arterioles and venules. The distribution of blood flow rates in these networks may affect the efficiency of oxygen transfer processes. Here, we investigate the distribution and correlation properties of blood flow velocities from numerical simulations in large 3D human intra-cortical vascular network (10000 segments) obtained from an anatomical database. In each segment, flow is solved from a 1D non-linear model taking account of the complex rheological properties of blood flow in microcirculation to deduce blood pressure, blood flow and red blood cell volume fraction distributions throughout the network. The network structural complexity is found to impart broad and spatially correlated Lagrangian velocity distributions, leading to power law transit time distributions. The origins of this behavior (existence of velocity correlations in capillary networks, influence of the coupling with the feeding arterioles and draining veins, topological disorder, complex blood rheology) are studied by comparison with results obtained in various model capillary networks of controlled disorder. ERC BrainMicroFlow GA615102, ERC ReactiveFronts GA648377.

  6. Characterisation and modelling of brain tissue for surgical simulation.

    Science.gov (United States)

    Mendizabal, A; Aguinaga, I; Sánchez, E

    2015-05-01

    Interactive surgical simulators capable of providing a realistic visual and haptic feedback to users are a promising technology for medical training and surgery planification. However, modelling the physical behaviour of human organs and tissues for surgery simulation remains a challenge. On the one hand, this is due to the difficulty to characterise the physical properties of biological soft tissues. On the other hand, the challenge still remains in the computation time requirements of real-time simulation required in interactive systems. Real-time surgical simulation and medical training must employ a sufficiently accurate and simple model of soft tissues in order to provide a realistic haptic and visual response. This study attempts to characterise the brain tissue at similar conditions to those that take place on surgical procedures. With this aim, porcine brain tissue is characterised, as a surrogate of human brain, on a rotational rheometer at low strain rates and large strains. In order to model the brain tissue with an adequate level of accuracy and simplicity, linear elastic, hyperelastic and quasi-linear viscoelastic models are defined. These models are simulated using the ABAQUS finite element platform and compared with the obtained experimental data. Copyright © 2015 Elsevier Ltd. All rights reserved.

  7. Alcohol-related brain damage in humans.

    Directory of Open Access Journals (Sweden)

    Amaia M Erdozain

    Full Text Available 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.

  8. D-galactose-induced brain ageing model

    DEFF Research Database (Denmark)

    Sadigh-Eteghad, Saeed; Majdi, Alireza; McCann, Sarah K.

    2017-01-01

    Animal models are commonly used in brain ageing research. Amongst these, models where rodents are exposed to d-galactose are held to recapitulate a number of features of ageing including neurobehavioral and neurochemical changes. However, results from animal studies are often inconsistent...

  9. 3D brain Organoids derived from pluripotent stem cells: promising experimental models for brain development and neurodegenerative disorders.

    Science.gov (United States)

    Lee, Chun-Ting; Bendriem, Raphael M; Wu, Wells W; Shen, Rong-Fong

    2017-08-20

    Three-dimensional (3D) brain organoids derived from human pluripotent stem cells (hPSCs), including embryonic stem cells (ESCs) and induced pluripotent stem cells (iPSCs), appear to recapitulate the brain's 3D cytoarchitectural arrangement and provide new opportunities to explore disease pathogenesis in the human brain. Human iPSC (hiPSC) reprogramming methods, combined with 3D brain organoid tools, may allow patient-derived organoids to serve as a preclinical platform to bridge the translational gap between animal models and human clinical trials. Studies using patient-derived brain organoids have already revealed novel insights into molecular and genetic mechanisms of certain complex human neurological disorders such as microcephaly, autism, and Alzheimer's disease. Furthermore, the combination of hiPSC technology and small-molecule high-throughput screening (HTS) facilitates the development of novel pharmacotherapeutic strategies, while transcriptome sequencing enables the transcriptional profiling of patient-derived brain organoids. Finally, the addition of CRISPR/Cas9 genome editing provides incredible potential for personalized cell replacement therapy with genetically corrected hiPSCs. This review describes the history and current state of 3D brain organoid differentiation strategies, a survey of applications of organoids towards studies of neurodevelopmental and neurodegenerative disorders, and the challenges associated with their use as in vitro models of neurological disorders.

  10. Models of human operators

    International Nuclear Information System (INIS)

    Knee, H.E.; Schryver, J.C.

    1991-01-01

    Models of human behavior and cognition (HB and C) are necessary for understanding the total response of complex systems. Many such models have come available over the past thirty years for various applications. Unfortunately, many potential model users remain skeptical about their practicality, acceptability, and usefulness. Such hesitancy stems in part to disbelief in the ability to model complex cognitive processes, and a belief that relevant human behavior can be adequately accounted for through the use of commonsense heuristics. This paper will highlight several models of HB and C and identify existing and potential applications in attempt to dispel such notions. (author)

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

    NARCIS (Netherlands)

    Hawrylycz, M.J.; Beckmann, Christian

    2012-01-01

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

  12. Neuronal substrates of sensory gating within the human brain.

    NARCIS (Netherlands)

    Grunwald, T.; Boutros, N.N.; Pezer, N.; Oertzen, J. von; Fernandez, G.S.E.; Schaller, C.; Elger, C.E.

    2003-01-01

    BACKGROUND: For the human brain, habituation to irrelevant sensory input is an important function whose failure is associated with behavioral disturbances. Sensory gating can be studied by recording the brain's electrical responses to repeated clicks: the P50 potential is normally reduced to the

  13. Common genetic variants influence human subcortical brain structures

    NARCIS (Netherlands)

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

    2015-01-01

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

  14. Common genetic variants influence human subcortical brain structures

    NARCIS (Netherlands)

    Hibar, D.P.; Stein, J.L.; Renteria, M.E.; Arias-Vasquez, A.; Desrivières, S.; Jahanshad, N.; Toro, R.; Wittfeld, K.; Abramovic, L.; Andersson, M.; Aribisala, B.S.; Armstrong, N.J.; Bernard, M.; Bohlken, M.M.; Biks, M.P.; Bralten, J.; Brown, A.A.; Chakravarty, M.M.; Chen, Q.; Ching, C.R.K.; Cuellar-Partida, G.; den Braber, A.; Giddaluru, S.; Goldman, A.L.; Grimm, O.; Guadalupe, T.; Hass, J.; Woldehawariat, G.; Holmes, A.J.; Hoogman, M.; Janowitz, D.; Jia, T.; Kim, S.; Klein, M.; Kraemer, B.; Lee, P.H.; Olde Loohuis, L.M.; Luciano, M.; Macare, C.; Mather, K.A.; Mattheisen, M.; Milaneschi, Y.; Nho, K.; Papmeyer, M.; Ramasamy, A.; Risacher, S.L.; Roiz-Santiañez, R.; Rose, E.J.; Salami, A.; Sämann, P.G.; Schmaal, L.; Schork, A.J.; Shin, J.; Strike, L.T.; Teumer, A.; Donkelaar, M.M.J.; van Eijk, K.R.; Walters, R.K.; Westlye, L.T.; Welan, C.D.; Winkler, A.M.; Zwiers, M.P.; Alhusaini, S.; Athanasiu, L.; Ehrlich, S.; Hakobjan, M.M.H.; Hartberg, C.B.; Haukvik, U.K.; Heister, A.J.G.A.M.; Hoehn, D.; Kasperaviciute, D.; Liewald, D.C.M.; Lopez, L.M.; Makkinje, R.R.; Matarin, M.; Naber, M.A.M.; Reese McKay, D.; Needham, M.; Nugent, A.C.; Pütz, B.; Royle, N.A.; Shen, L.; Sprooten, E.; Trabzuni, D.; van der Marel, S.S.L.; van Hulzen, K.J.E.; Walton, E.; Wolf, C.; Almasy, L.; Ames, D.; Arepalli, S.; Assareh, A.A.; Bastin, M.E.; Brodaty, H.; Bulayeva, K.B.; Carless, M.A.; Cichon, S.; Corvin, A.; Curran, J.E.; Czisch, M.; de Zubicaray, G.I.; Dillman, A.; Duggirala, R.; Dyer, T.D.; Erk, S.; Fedko, I.O.; Ferrucci, L.; Foroud, T.M.; Fox, P.T.; Fukunaga, M.; Gibbs, J.R.; Göring, H.H.H.; Green, R.C.; Guelfi, S.; Hansell, N.K.; Hartman, C.A.; Hegenscheid, K.; Heinz, A.; Hernandez, D.G.; Heslenfeld, D.J.; Hoekstra, P.J.; Holsboer, F.; Homuth, G.; Hottenga, J.J.; Ikeda, M.; Jack, C.R., Jr.; Jenkinson, M.; Johnson, R.; Kanai, R.; Keil, M.; Kent, J.W. Jr.; Kochunov, P.; Kwok, J.B.; Lawrie, S.M.; Liu, X.; Longo, D.L.; McMahon, K.L.; Meisenzahl, E.; Melle, I.; Mohnke, S.; Montgomery, G.W.; Mostert, J.C.; Mühleisen, T.W.; Nalls, M.A.; Nichols, T.E.; Nilsson, L.G.; Nöthen, M.M.; Ohi, K.; Olvera, R.L.; Perez-Iglesias, R.; Pike, G.B.; Potkin, S.G.; Reinvang, I.; Reppermund, S.; Rietschel, M.; Romanczuk-Seiferth, N.; Rosen, G.D.; Rujescu, D.; Schnell, K.; Schofield, P.R.; Smith, C.; Steen, V.M.; Sussmann, J.E.; Thalamuthu, A.; Toga, A.W.; Traynor, B.J.; Troncoso, J.; Turner, J.A.; Valdés Hernández, M.C.; van t Ent, D.; van der Brug, M.; van der Wee, N.J.A.; van Tol, M.J.; Veltman, D.J.; Wassink, T.H.; Westmann, E.; Zielke, R.H.; Zonderman, A.B.; Ashbrook, D.G.; Hager, R.; Lu, L.; McMahon, F.J.; Morris, D.W.; Williams, R.W.; Brunner, H.G.; Buckner, R.L.; Buitelaar, J.K.; Cahn, W.; Calhoun, V.D.; Cavalleri, G.L.; Crespo-Facorro, B.; Dale, A.M.; Davies, G.E.; Delanty, N.; Depondt, C.; Djurovic, S.; Drevets, W.C.; Espeseth, T.; Gollub, R.L.; Ho, B.C.; Hoffmann, W.; Hosten, N.; Kahn, R.S.; Le Hellard, S.; Meyer-Lindenberg, A.; Müller-Myhsok, B.; Nauck, M.; Nyberg, L.; Pandolfo, M.; Penninx, B.W.J.H.; Roffman, J.L.; Sisodiya, SM; Smoller, J.W.; van Bokhoven, H.; van Haren, N.E.M.; Völzke, H.; Walter, H.; Weiner, M.W.; Wen, W.; White, T.; Agartz, I.; Andreassen, O.A.; Blangero, J.; Boomsma, D.I.; Brouwer, R.M.; Cannon, D.M.; Cookson, M.R.; de Geus, E.J.C.; Deary, I.J.; Donohoe, G.; Fernandez, G.; Fisher, S.E.; Francks, C.; Glahn, D.C.; Grabe, H.J.; Gruber, O.; Hardy, J.; Hashimoto, R.; Hulshoff Pol, H.E.; Jönsson, E.G.; Kloszewska, I.; Lovestone, S.; Mattay, V.S.; Mecocci, P.; McDonald, C.; McIntosh, A.M.; Ophoff, R.A.; Paus, T.; Pausova, Z.; Ryten, M.; Sachdev, P.S.; Saykin, A.J.; Simmons, A.; Singleton, A.; Soininen, H.; Wardlaw, J.M.; Weale, M.E.; Weinberger, D.R.; Adams, H.H.H.; Launer, L.J.; Seiler, S.; Schmidt, R.; Chauhan, G.; Satizabal, C.L.; Becker, J.T.; Yanek, L.; van der Lee, S.J.; Ebling, M.; Fischl, B.; Longstreth, Jr. W.T.; Greve, D.; Schmidt, H.; Nyquist, P.; Vinke, L.N.; van Duijn, C.M.; Xue, L.; Mazoyer, B.; Bis, J.C.; Gudnason, V.; Seshadri, S.; Arfan Ikram, M.; Martin, N.G.; Wright, M.J.; Schumann, G.; Franke, B.; Thompson, P.M.; Medland, S.E.

    2015-01-01

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

  15. Common genetic variants influence human subcortical brain structures

    NARCIS (Netherlands)

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

    2015-01-01

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

  16. MR-visible brain water content in human acute stroke

    DEFF Research Database (Denmark)

    Gideon, P; Rosenbaum, S; Sperling, B

    1999-01-01

    Quantification of metabolite concentrations by proton magnetic resonance spectroscopy (1H-MRS) in the human brain using water as an internal standard is based on the assumption that water content does not change significantly in pathologic brain tissue. To test this, we used 1H-MRS to estimate...

  17. Toward discovery science of human brain function

    DEFF Research Database (Denmark)

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

    2010-01-01

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

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

    DEFF Research Database (Denmark)

    Rasmussen, S; Bock, E; Warecka, K

    1980-01-01

    The glial fibrillary acidic protein (GFA) content of 58 human brain tumours was determined by quantitative immunoelectrophoresis, using monospecific antibody against GFA. Astrocytomas, glioblastomas, oligodendrogliomas, spongioblastomas, ependymomas and medulloblastomas contained relatively high...

  19. Evaluation of cat brain infarction model using microPET

    International Nuclear Information System (INIS)

    Lee, J. J.; Lee, D. S.; Kim, J. H.; Hwang, D. W.; Jung, J. G.; Lee, M. C; Lim, S. M

    2004-01-01

    PET has some disadvantage in the imaging of small animal due to poor resolution. With the advance of microPET scanner, it is possible to image small animals. However, the image quality was not so much satisfactory as human image. As cats have relatively large sized brain, cat brain imaging was superior to mice or rat. In this study, we established the cat brain infarction model and evaluate it and its temporal change using microPET scanner. Two adult male cats were used. Anesthesia was done with xylazine and ketamine HCl. A burr hole was made at 1cm right lateral to the bregma. Collagenase type IV 10 ul was injected using 30G needle for 5 minutes to establish the infarction model. F-18 FDG microPET (Concorde Microsystems Inc., Knoxville. TN) scans were performed 1. 11 and 32 days after the infarction. In addition. 18F-FDG PET scans were performed using Gemini PET scanner (Philips medical systems. CA, USA) 13 and 47 days after the infarction. Two cat brain infarction models were established. The glucose metabolism of an infraction lesion improved with time. An infarction lesion was also distinguishable in the Gemini PET scan. We successfully established the cat brain infarction model and evaluated the infarcted lesion and its temporal change using F-18 FDG microPET scanner

  20. Evaluation of cat brain infarction model using microPET

    Energy Technology Data Exchange (ETDEWEB)

    Lee, J. J.; Lee, D. S.; Kim, J. H.; Hwang, D. W.; Jung, J. G.; Lee, M. C [College of Medicine, Seoul National University, Seoul (Korea, Republic of); Lim, S. M [Korea Institute of Radiological and Medical Sciences, Seoul (Korea, Republic of)

    2004-07-01

    PET has some disadvantage in the imaging of small animal due to poor resolution. With the advance of microPET scanner, it is possible to image small animals. However, the image quality was not so much satisfactory as human image. As cats have relatively large sized brain, cat brain imaging was superior to mice or rat. In this study, we established the cat brain infarction model and evaluate it and its temporal change using microPET scanner. Two adult male cats were used. Anesthesia was done with xylazine and ketamine HCl. A burr hole was made at 1cm right lateral to the bregma. Collagenase type IV 10 ul was injected using 30G needle for 5 minutes to establish the infarction model. F-18 FDG microPET (Concorde Microsystems Inc., Knoxville. TN) scans were performed 1. 11 and 32 days after the infarction. In addition. 18F-FDG PET scans were performed using Gemini PET scanner (Philips medical systems. CA, USA) 13 and 47 days after the infarction. Two cat brain infarction models were established. The glucose metabolism of an infraction lesion improved with time. An infarction lesion was also distinguishable in the Gemini PET scan. We successfully established the cat brain infarction model and evaluated the infarcted lesion and its temporal change using F-18 FDG microPET scanner.

  1. Noninvasive Stimulation of the Human Brain

    DEFF Research Database (Denmark)

    Di Lazzaro, Vincenzo; Rothwell, John; Capogna, Marco

    2017-01-01

    Noninvasive brain stimulation methods, such as transcranial electric stimulation and transcranial magnetic stimulation are widely used tools for both basic research and clinical applications. However, the cortical circuits underlying their effects are poorly defined. Here we review the current...

  2. The resting human brain and motor learning

    OpenAIRE

    Albert, Neil B.; Robertson, Edwin M.; Miall, R. Chris

    2009-01-01

    Summary Functionally related brain networks are engaged even in the absence of an overt behavior. The role of this resting state activity, evident as low-frequency fluctuations of BOLD (see [1] for review, [2?4]) or electrical [5, 6] signals, is unclear. Two major proposals are that resting state activity supports introspective thought or supports responses to future events [7]. An alternative perspective is that the resting brain actively and selectively processes previous experiences [8]. H...

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

    DEFF Research Database (Denmark)

    Rasmussen, S; Bock, E; Warecka, K

    1980-01-01

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

  4. Optogenetic control of human neurons in organotypic brain cultures

    DEFF Research Database (Denmark)

    Andersson, My; Avaliani, Natalia; Svensson, Andreas

    2016-01-01

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

  5. Reflectance diffuse optical tomography. Its application to human brain mapping

    International Nuclear Information System (INIS)

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

    2005-01-01

    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. (author)

  6. Modeling high dimensional multichannel brain signals

    KAUST Repository

    Hu, Lechuan

    2017-03-27

    In this paper, our goal is to model functional and effective (directional) connectivity in network of multichannel brain physiological signals (e.g., electroencephalograms, local field potentials). The primary challenges here are twofold: first, there are major statistical and computational difficulties for modeling and analyzing high dimensional multichannel brain signals; second, there is no set of universally-agreed measures for characterizing connectivity. To model multichannel brain signals, our approach is to fit a vector autoregressive (VAR) model with sufficiently high order so that complex lead-lag temporal dynamics between the channels can be accurately characterized. However, such a model contains a large number of parameters. Thus, we will estimate the high dimensional VAR parameter space by our proposed hybrid LASSLE method (LASSO+LSE) which is imposes regularization on the first step (to control for sparsity) and constrained least squares estimation on the second step (to improve bias and mean-squared error of the estimator). Then to characterize connectivity between channels in a brain network, we will use various measures but put an emphasis on partial directed coherence (PDC) in order to capture directional connectivity between channels. PDC is a directed frequency-specific measure that explains the extent to which the present oscillatory activity in a sender channel influences the future oscillatory activity in a specific receiver channel relative all possible receivers in the network. Using the proposed modeling approach, we have achieved some insights on learning in a rat engaged in a non-spatial memory task.

  7. Endogenous neurogenesis in the human brain following cerebral infarction.

    Science.gov (United States)

    Minger, Stephen L; Ekonomou, Antigoni; Carta, Eloisa M; Chinoy, Amish; Perry, Robert H; Ballard, Clive G

    2007-01-01

    Increased endogenous neurogenesis has a significant regenerative role in many experimental models of cerebrovascular diseases, but there have been very few studies in humans. We therefore examined whether there was evidence of altered endogenous neurogenesis in an 84-year-old patient who suffered a cerebrovascular accident 1 week prior to death. Using antibodies that specifically label neural stem/neural progenitor cells, we examined the presence of immunopositive cells around and distant from the infarcted area, and compared this with a control, age-matched individual. Interestingly, a large number of neural stem cells, vascular endothelial growth factor-immunopositive cells and new blood vessels were observed only around the region of infarction, and none in the corresponding brain areas of the healthy control. In addition, an increased number of neural stem cells was observed in the neurogenic region of the lateral ventricle wall. Our results suggest increased endogenous neurogenesis associated with neovascularization and migration of newly-formed cells towards a region of cerebrovascular damage in the adult human brain and highlight possible mechanisms underlying this process.

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

    Science.gov (United States)

    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]. Copyright © 2016 Elsevier Ltd. All rights reserved.

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

    DEFF Research Database (Denmark)

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

    2017-01-01

    OBJECTIVE: Surgery launches a systemic inflammatory reaction that reaches the brain and associates with immune activation and cognitive decline. Although preclinical studies have in part described this systemic-to-brain signaling pathway, we lack information on how these changes appear in humans....... This study examines the short- and long-term impact of abdominal surgery on the human brain immune system by positron emission tomography (PET) in relation to blood immune reactivity, plasma inflammatory biomarkers, and cognitive function. METHODS: Eight males undergoing prostatectomy under general...... anesthesia were included. Prior to surgery (baseline), at postoperative days 3 to 4, and after 3 months, patients were examined using [11C]PBR28 brain PET imaging to assess brain immune cell activation. Concurrently, systemic inflammatory biomarkers, ex vivo blood tests on immunoreactivity...

  10. Do glutathione levels decline in aging human brain?

    Science.gov (United States)

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

    2016-04-01

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

  11. Human brain glycogen content and metabolism: implications on its role in brain energy metabolism

    OpenAIRE

    Oz, Gülin; Seaquist, Elizabeth R; Kumar, Anjali; Criego, Amy B; Benedict, Luke E; Rao, Jyothi P; Henry, Pierre-Gilles; Van De Moortele, Pierre-Francois; Gruetter, Rolf

    2007-01-01

    The adult brain relies on glucose for its energy needs and stores it in the form of glycogen, primarily in astrocytes. Animal and culture studies indicate that brain glycogen may support neuronal function when the glucose supply from the blood is inadequate and/or during neuronal activation. However, the concentration of glycogen and rates of its metabolism in the human brain are unknown. We used in vivo localized 13C-NMR spectroscopy to measure glycogen content and turnover in the human brai...

  12. Human brain activity with functional NIR optical imager

    Science.gov (United States)

    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.

  13. Computational human body models

    NARCIS (Netherlands)

    Wismans, J.S.H.M.; Happee, R.; Dommelen, J.A.W. van

    2005-01-01

    Computational human body models are widely used for automotive crashsafety research and design and as such have significantly contributed to a reduction of traffic injuries and fatalities. Currently crash simulations are mainly performed using models based on crash-dummies. However crash dummies

  14. Skull and cerebrospinal fluid effects on microwave radiation propagation in human brain

    Science.gov (United States)

    Ansari, M. A.; Zarei, M.; Akhlaghipour, N.; Niknam, A. R.

    2017-12-01

    The determination of microwave absorption distribution in the human brain is necessary for the detection of brain tumors using thermo-acoustic imaging and for removing them using hyperthermia treatment. In contrast to ionizing radiation, hyperthermia treatment can be applied to remove tumors inside the brain without the concern of including secondary malignancies, which typically form from the neuronal cells of the septum pellucidum. The aim of this study is to determine the microwave absorption distribution in an adult human brain and to study the effects of skull and cerebrospinal fluid on the propagation of microwave radiation inside the brain. To this end, we simulate the microwave absorption distribution in a realistic adult brain model (Colin 27) using the mesh-based Monte Carlo (MMC) method. This is because in spite of there being other numerical methods, the MMC does not require a large memory, even for complicated geometries, and its algorithm is simple and easy to implement with low computational cost. The brain model is constructed using high-resolution (1 mm isotropic voxel) and low noise magnetic resonance imaging (MRI) scans and its volume contains 181×217×181 voxels, covering the brain completely. Using the MMC method, the radiative transport equation is solved and the absorbed microwave energy distribution in different brain regions is obtained without any fracture or anomaly. The simulation results show that the skull and cerebrospinal fluid guide the microwave radiation and suppress its penetration through deep brain compartments as a shielding factor. These results reveal that the MMC can be used to predict the amount of required energy to increase the temperature inside the tumour during hyperthermia treatment. Our results also show why a deep tumour inside an adult human brain cannot be efficiently treated using hyperthermia treatment. Finally, the accuracy of the presented numerical method is verified using the signal flow graph technique.

  15. The intrinsic geometry of the human brain connectome.

    Science.gov (United States)

    Ye, Allen Q; Ajilore, Olusola A; Conte, Giorgio; GadElkarim, Johnson; Thomas-Ramos, Galen; Zhan, Liang; Yang, Shaolin; Kumar, Anand; Magin, Richard L; G Forbes, Angus; Leow, Alex D

    2015-12-01

    This paper describes novel methods for constructing the intrinsic geometry of the human brain connectome using dimensionality-reduction techniques. We posit that the high-dimensional, complex geometry that represents this intrinsic topology can be mathematically embedded into lower dimensions using coupling patterns encoded in the corresponding brain connectivity graphs. We tested both linear and nonlinear dimensionality-reduction techniques using the diffusion-weighted structural connectome data acquired from a sample of healthy subjects. Results supported the nonlinearity of brain connectivity data, as linear reduction techniques such as the multidimensional scaling yielded inferior lower-dimensional embeddings. To further validate our results, we demonstrated that for tractography-derived structural connectome more influential regions such as rich-club members of the brain are more centrally mapped or embedded. Further, abnormal brain connectivity can be visually understood by inspecting the altered geometry of these three-dimensional (3D) embeddings that represent the topology of the human brain, as illustrated using simulated lesion studies of both targeted and random removal. Last, in order to visualize brain's intrinsic topology we have developed software that is compatible with virtual reality technologies, thus allowing researchers to collaboratively and interactively explore and manipulate brain connectome data.

  16. Insulin action in the human brain: evidence from neuroimaging studies.

    Science.gov (United States)

    Kullmann, S; Heni, M; Fritsche, A; Preissl, H

    2015-06-01

    Thus far, little is known about the action of insulin in the human brain. Nonetheless, recent advances in modern neuroimaging techniques, such as functional magnetic resonance imaging (fMRI) or magnetoencephalography (MEG), have made it possible to investigate the action of insulin in the brain in humans, providing new insights into the pathogenesis of brain insulin resistance and obesity. Using MEG, the clinical relevance of the action of insulin in the brain was first identified, linking cerebral insulin resistance with peripheral insulin resistance, genetic predisposition and weight loss success in obese adults. Although MEG is a suitable tool for measuring brain activity mainly in cortical areas, fMRI provides high spatial resolution for cortical as well as subcortical regions. Thus, the action of insulin can be detected within all eating behaviour relevant regions, which include regions deeply located within the brain, such as the hypothalamus, midbrain and brainstem, as well as regions within the striatum. In this review, we outline recent advances in the field of neuroimaging aiming to investigate the action of insulin in the human brain using different routes of insulin administration. fMRI studies have shown a significant insulin-induced attenuation predominantly in the occipital and prefrontal cortical regions and the hypothalamus, successfully localising insulin-sensitive brain regions in healthy, mostly normal-weight individuals. However, further studies are needed to localise brain areas affected by insulin resistance in obese individuals, which is an important prerequisite for selectively targeting brain insulin resistance in obesity. © 2015 British Society for Neuroendocrinology.

  17. Cellular immune surveillance of central nervous system bypasses blood-brain barrier and blood-cerebrospinal-fluid barrier: revealed with the New Marburg cerebrospinal-fluid model in healthy humans.

    Science.gov (United States)

    Kleine, Tilmann O

    2015-03-01

    In healthy human brain/spinal cord, blood capillaries and venules are locked differently with junctions and basement membrane (blood-brain barrier, blood-venule barrier). In choroid plexus, epithelial tight junctions and basement membrane lock blood-cerebrospinal-fluid (CSF) barrier. Lymphocytic cell data, quantified with multicolour flow-cytometry or immuno-cytochemical methods in sample pairs of lumbar CSF, ventrictricular CSF and peripheral venous blood, are taken from references; similarly, data of thoracic duct chyle and blood sample pairs. Through three circumventricular organs (median eminence, organum vasculosum lamina terminalis, area postrema), 15-30 μl blood are pressed by blood pressure through fenestrated capillaries, matrix/basement membrane spaces and ependyma cell lacks into ventricular/suboccipital CSF to generate CD3(+) , CD4(+) , CD8(+) , CD3(+) HLA-DR(+) , CD16(+) 56(+) 3(-) NK, CD19(+) 3(-) B subsets; some B, few NK cells adhere in circumventricular organs. Into lumbar CSF, 10-15 μl thoracic chyle with five lymphocyte subsets (without CD3(+) HLA-DR(+) cells) reflux, when CSF drains out with to-and-fro movements of chyle/CSF along nerve roots. Lymphocytes in lumbar CSF represent a mixture of blood and lymph lymphocytic cells with similar HLA-DR(+) CD3(+) cell counts in ventricular and lumbar CSF, higher CD3(+) , CD4(+) , CD8(+) subsets in lumbar CSF, and few NK and B cells due to absorption in circumventricular organs. The Marburg CSF Model reflects origin and turnover of lymphatic cells in CSF realistically; the model differs from ligand-multistep processes of activated lymphocytes through blood-brain-, blood-venule-, and blood-CSF-barriers; because transfer of inactivated native lymphocytes through the barriers is not found with healthy humans, although described so in literature. © 2015 International Society for Advancement of Cytometry.

  18. A new antigen retrieval technique for human brain tissue.

    Science.gov (United States)

    Alelú-Paz, Raúl; Iturrieta-Zuazo, Ignacio; Byne, William; Haroutunian, Vahram; García-Villanueva, Mercedes; Rábano, Alberto; García-Amado, María; Prensa, Lucía; Giménez-Amaya, José Manuel

    2008-01-01

    Immunohistochemical staining of tissues is a powerful tool used to delineate the presence or absence of an antigen. During the last 30 years, antigen visualization in human brain tissue has been significantly limited by the masking effect of fixatives. In the present study, we have used a new method for antigen retrieval in formalin-fixed human brain tissue and examined the effectiveness of this protocol to reveal masked antigens in tissues with both short and long formalin fixation times. This new method, which is based on the use of citraconic acid, has not been previously utilized in brain tissue although it has been employed in various other tissues such as tonsil, ovary, skin, lymph node, stomach, breast, colon, lung and thymus. Thus, we reported here a novel method to carry out immunohistochemical studies in free-floating human brain sections. Since fixation of brain tissue specimens in formaldehyde is a commonly method used in brain banks, this new antigen retrieval method could facilitate immunohistochemical studies of brains with prolonged formalin fixation times.

  19. An Evolutionary Game Theory Model of Spontaneous Brain Functioning.

    Science.gov (United States)

    Madeo, Dario; Talarico, Agostino; Pascual-Leone, Alvaro; Mocenni, Chiara; Santarnecchi, Emiliano

    2017-11-22

    Our brain is a complex system of interconnected regions spontaneously organized into distinct networks. The integration of information between and within these networks is a continuous process that can be observed even when the brain is at rest, i.e. not engaged in any particular task. Moreover, such spontaneous dynamics show predictive value over individual cognitive profile and constitute a potential marker in neurological and psychiatric conditions, making its understanding of fundamental importance in modern neuroscience. Here we present a theoretical and mathematical model based on an extension of evolutionary game theory on networks (EGN), able to capture brain's interregional dynamics by balancing emulative and non-emulative attitudes among brain regions. This results in the net behavior of nodes composing resting-state networks identified using functional magnetic resonance imaging (fMRI), determining their moment-to-moment level of activation and inhibition as expressed by positive and negative shifts in BOLD fMRI signal. By spontaneously generating low-frequency oscillatory behaviors, the EGN model is able to mimic functional connectivity dynamics, approximate fMRI time series on the basis of initial subset of available data, as well as simulate the impact of network lesions and provide evidence of compensation mechanisms across networks. Results suggest evolutionary game theory on networks as a new potential framework for the understanding of human brain network dynamics.

  20. Development and Characterization of a Brain Endothelial Cell Phenotype using Human Induced Pluripotent Stem Cells

    DEFF Research Database (Denmark)

    Goldeman, Charlotte; Saaby, Lasse; Holst, Bjørn

    The transport of substances from blood to brain is regulated by the blood-brain barrier (BBB), i.e. the barrier properties of the brain endothelium. The endothelium restricts the transport into the brain of the majority of new drug candidates. Cultured monolayers of brain endothelial cells can...... be used to investigate drug transport in vitro, and screen candidates for permeation properties. One recent approach is to develop in vitro models of the BBB using human induced pluripotent stem cells (hIPSCs) as described by Stebbins et al. (2015).The aim of the present study was to investigate whether...... the published protocols were generically applicable and thus to develop and characterize in vitro models of the BBB using hIPSCs from different sources. Two stem cell lines, Bioni010-C and WTSli024-A, were seeded and maintained on Matrigel in mTesR1 media. Cells were then seeded as single cells at different...

  1. Modeling High-Dimensional Multichannel Brain Signals

    KAUST Repository

    Hu, Lechuan

    2017-12-12

    Our goal is to model and measure functional and effective (directional) connectivity in multichannel brain physiological signals (e.g., electroencephalograms, local field potentials). The difficulties from analyzing these data mainly come from two aspects: first, there are major statistical and computational challenges for modeling and analyzing high-dimensional multichannel brain signals; second, there is no set of universally agreed measures for characterizing connectivity. To model multichannel brain signals, our approach is to fit a vector autoregressive (VAR) model with potentially high lag order so that complex lead-lag temporal dynamics between the channels can be captured. Estimates of the VAR model will be obtained by our proposed hybrid LASSLE (LASSO + LSE) method which combines regularization (to control for sparsity) and least squares estimation (to improve bias and mean-squared error). Then we employ some measures of connectivity but put an emphasis on partial directed coherence (PDC) which can capture the directional connectivity between channels. PDC is a frequency-specific measure that explains the extent to which the present oscillatory activity in a sender channel influences the future oscillatory activity in a specific receiver channel relative to all possible receivers in the network. The proposed modeling approach provided key insights into potential functional relationships among simultaneously recorded sites during performance of a complex memory task. Specifically, this novel method was successful in quantifying patterns of effective connectivity across electrode locations, and in capturing how these patterns varied across trial epochs and trial types.

  2. Development of human brain structural networks through infancy and childhood.

    Science.gov (United States)

    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

    2015-05-01

    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. © The Author 2013. Published by Oxford University Press. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.

  3. Gene expression in the aging human brain: an overview.

    Science.gov (United States)

    Mohan, Adith; Mather, Karen A; Thalamuthu, Anbupalam; Baune, Bernhard T; Sachdev, Perminder S

    2016-03-01

    The review aims to provide a summary of recent developments in the study of gene expression in the aging human brain. Profiling differentially expressed genes or 'transcripts' in the human brain over the course of normal aging has provided valuable insights into the biological pathways that appear activated or suppressed in late life. Genes mediating neuroinflammation and immune system activation in particular, show significant age-related upregulation creating a state of vulnerability to neurodegenerative and neuropsychiatric disease in the aging brain. Cellular ionic dyshomeostasis and age-related decline in a host of molecular influences on synaptic efficacy may underlie neurocognitive decline in later life. Critically, these investigations have also shed light on the mobilization of protective genetic responses within the aging human brain that help determine health and disease trajectories in older age. There is growing interest in the study of pre and posttranscriptional regulators of gene expression, and the role of noncoding RNAs in particular, as mediators of the phenotypic diversity that characterizes human brain aging. Gene expression studies in healthy brain aging offer an opportunity to unravel the intricately regulated cellular underpinnings of neurocognitive aging as well as disease risk and resiliency in late life. In doing so, new avenues for early intervention in age-related neurodegenerative disease could be investigated with potentially significant implications for the development of disease-modifying therapies.

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

    Science.gov (United States)

    Dixon-Salazar, Tracy J; Gleeson, Joseph G

    2010-12-01

    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. © 2010 New York Academy of Sciences.

  5. A hollow fiber system for simple generation of human brain organoids.

    Science.gov (United States)

    Zhu, Yujuan; Wang, Li; Yin, Fangchao; Yu, Yue; Wang, Yaqing; Liu, Hui; Wang, Hui; Sun, Ning; Liu, Haitao; Qin, Jianhua

    2017-09-18

    3D organoids exhibit near-physiological morphogenesis and histology relying on the self-organization of human pluripotent stem cells (hPSCs), representing a new class of in vitro model for studying developmental biology and diseases. An engineered approach is highly desirable to generate sufficient organoids in a simple and efficient manner. Herein, we present a new strategy for the simple formation of massive human brain organoids from hiPSCs within a hollow fiber reactor system by combining fiber materials with the developmental biology principle. A thin and finely adjustable calcium alginate (CaA) core-shell fiber was constructed using a multilayer coaxial laminar flow microfluidic system. The meter-long hollow fibers enabled neural differentiation of hiPSCs and simple formation of abundant brain organoids in a 3D matrix. The generated brain organoids displayed essential features of human brain organogenesis, including polarized neuroepithelium, cell type heterogeneity and discrete brain regions, resembling the early brain development. This approach is simple and easy to operate, which allows for simplified formation of massive brain organoids, overcoming the tedious procedures in conventional methods. In particular, the facile and scalable characteristics of hollow fibers are compatible with real-time observation and monitoring, as well as flexible tissue manipulations for downstream biological analysis. It might also provide a new platform to advance stem cell-derived organoid models and their utility in biomedical applications.

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

    Directory of Open Access Journals (Sweden)

    Britton Robert S

    2009-04-01

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

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

    Science.gov (United States)

    Miller, Geoffrey F.; Penke, Lars

    2007-01-01

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

  8. Human migraine models

    DEFF Research Database (Denmark)

    Iversen, Helle Klingenberg

    2001-01-01

    The need for experimental models is obvious. In animal models it is possible to study vascular responses, neurogenic inflammation, c-fos expression etc. However, the pathophysiology of migraine remains unsolved, why results from animal studies not directly can be related to the migraine attack......, which is a human experience. A set-up for investigations of experimental headache and migraine in humans, has been evaluated and headache mechanisms explored by using nitroglycerin and other headache-inducing agents. Nitric oxide (NO) or other parts of the NO activated cascade seems to be responsible...... for the induced headache and migraine. Perspectives are discussed....

  9. Three-dimensional morphology of the human embryonic brain

    Directory of Open Access Journals (Sweden)

    N. Shiraishi

    2015-09-01

    Full Text Available The morphogenesis of the cerebral vesicles and ventricles was visualized in 3D movies using images derived from human embryo specimens between Carnegie stage 13 and 23 from the Kyoto Collection. These images were acquired with a magnetic resonance microscope equipped with a 2.35-T superconducting magnet. Three-dimensional images using the same scale demonstrated brain development and growth effectively. The non-uniform thickness of the brain tissue, which may indicate brain differentiation, was visualized with thickness-based surface color mapping. A closer view was obtained of the unique and complicated differentiation of the rhombencephalon, especially with regard to the internal view and thickening of the brain tissue. The present data contribute to a better understanding of brain and cerebral ventricle development.

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

    Directory of Open Access Journals (Sweden)

    Jun-Feng Feng

    2017-07-01

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

  11. Outer brain barriers in rat and human development

    DEFF Research Database (Denmark)

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

    2015-01-01

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

  12. Functional connectivity hubs in the human brain.

    Science.gov (United States)

    Tomasi, Dardo; Volkow, Nora D

    2011-08-01

    Brain networks appear to have few and well localized regions with high functional connectivity density (hubs) for fast integration of neural processing, and their dysfunction could contribute to neuropsychiatric diseases. However the variability in the distribution of these brain hubs is unknown due in part to the overwhelming computational demands associated to their localization. Recently we developed a fast algorithm to map the local functional connectivity density (lFCD). Here we extend our method to map the global density (gFDC) taking advantage of parallel computing. We mapped the gFCD in the brain of 1031 subjects from the 1000 Functional Connectomes project and show that the strongest hubs are located in regions of the default mode network (DMN) and in sensory cortices, whereas subcortical regions exhibited the weakest hubs. The strongest hubs were consistently located in ventral precuneus/cingulate gyrus (previously identified by other analytical methods including lFCD) and in primary visual cortex (BA 17/18), which highlights their centrality to resting connectivity networks. In contrast and after rescaling, hubs in prefrontal regions had lower gFCD than lFCD, which suggests that their local functional connectivity (as opposed to long-range connectivity) prevails in the resting state. The power scaling of the probability distribution of gFCD hubs (as for lFCD) was consistent across research centers further corroborating the "scale-free" topology of brain networks. Within and between-subject variability for gFCD were twice than that for lFCD (20% vs. 12% and 84% vs. 34%, respectively) suggesting that gFCD is more sensitive to individual differences in functional connectivity. Published by Elsevier Inc.

  13. Brain-inspired Stochastic Models and Implementations

    KAUST Repository

    Al-Shedivat, Maruan

    2015-05-12

    One of the approaches to building artificial intelligence (AI) is to decipher the princi- ples of the brain function and to employ similar mechanisms for solving cognitive tasks, such as visual perception or natural language understanding, using machines. The recent breakthrough, named deep learning, demonstrated that large multi-layer networks of arti- ficial neural-like computing units attain remarkable performance on some of these tasks. Nevertheless, such artificial networks remain to be very loosely inspired by the brain, which rich structures and mechanisms may further suggest new algorithms or even new paradigms of computation. In this thesis, we explore brain-inspired probabilistic mechanisms, such as neural and synaptic stochasticity, in the context of generative models. The two questions we ask here are: (i) what kind of models can describe a neural learning system built of stochastic components? and (ii) how can we implement such systems e ̆ciently? To give specific answers, we consider two well known models and the corresponding neural architectures: the Naive Bayes model implemented with a winner-take-all spiking neural network and the Boltzmann machine implemented in a spiking or non-spiking fashion. We propose and analyze an e ̆cient neuromorphic implementation of the stochastic neu- ral firing mechanism and study the e ̄ects of synaptic unreliability on learning generative energy-based models implemented with neural networks.

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

    Energy Technology Data Exchange (ETDEWEB)

    1991-04-01

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

  15. The metabolism of the human brain studied with positron emission tomography

    International Nuclear Information System (INIS)

    Greitz, T.; Ingvar, D.H.; Widen, L.

    1985-01-01

    This volume presents coverage of the use of positron emission tomography (PET) to study the human brain. The contributors assess new developments in high-resolution positron emission tomography, cyclotrons, radiochemistry, and tracer kinetic models, and explore the use of PET in brain energy metabolism, blood flow, and protein synthesis measurements, receptor analysis, and pH determinations, In addition, they discuss the relevance and applications of positron emission tomography from the perspectives of physiology, neurology, and psychiatry

  16. Intraoperative Functional Ultrasound Imaging of Human Brain Activity

    OpenAIRE

    Imbault, Marion; Chauvet, Dorian; Gennisson, Jean-Luc; Capelle, Laurent; Tanter, Mickael

    2017-01-01

    International audience; The functional mapping of brain activity is essential to perform optimal glioma surgery and to minimize the risk of postoperative deficits. We introduce a new, portable neuroimaging modality of the human brain based on functional ultrasound (fUS) for deep functional cortical mapping. Using plane-wave transmissions at an ultrafast frame rate (1 kHz), fUS is performed during surgery to measure transient changes in cerebral blood volume with a high spatiotemporal resoluti...

  17. Drosophila melanogaster as a Model Organism of Brain Diseases

    Directory of Open Access Journals (Sweden)

    Werner Paulus

    2009-02-01

    Full Text Available Drosophila melanogaster has been utilized to model human brain diseases. In most of these invertebrate transgenic models, some aspects of human disease are reproduced. Although investigation of rodent models has been of significant impact, invertebrate models offer a wide variety of experimental tools that can potentially address some of the outstanding questions underlying neurological disease. This review considers what has been gleaned from invertebrate models of neurodegenerative diseases, including Alzheimer’s disease, Parkinson’s disease, metabolic diseases such as Leigh disease, Niemann-Pick disease and ceroid lipofuscinoses, tumor syndromes such as neurofibromatosis and tuberous sclerosis, epilepsy as well as CNS injury. It is to be expected that genetic tools in Drosophila will reveal new pathways and interactions, which hopefully will result in molecular based therapy approaches.

  18. Distribution of vesicular glutamate transporters in the human brain

    Directory of Open Access Journals (Sweden)

    Erika eVigneault

    2015-03-01

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

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

    International Nuclear Information System (INIS)

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

    2005-01-01

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

  20. A Mind of Three Minds: Evolution of the Human Brain

    Science.gov (United States)

    MacLean, Paul D.

    1978-01-01

    The author examines the evolutionary and neural roots of a triune intelligence comprised of a primal mind, an emotional mind, and a rational mind. A simple brain model and some definitions of unfamiliar behavioral terms are included. (Author/MA)

  1. Endocannabinoids modulate human blood-brain barrier permeability in vitro.

    Science.gov (United States)

    Hind, William H; Tufarelli, Cristina; Neophytou, Maria; Anderson, Susan I; England, Timothy J; O'Sullivan, Saoirse E

    2015-06-01

    Endocannabinoids alter permeability at various epithelial barriers, and cannabinoid receptors and endocannabinoid levels are elevated by stroke, with potential neuroprotective effects. We therefore explored the role of endocannabinoids in modulating blood-brain barrier (BBB) permeability in normal conditions and in an ischaemia/reperfusion model. Human brain microvascular endothelial cell and astrocyte co-cultures modelled the BBB. Ischaemia was modelled by oxygen-glucose deprivation (OGD) and permeability was measured by transepithelial electrical resistance. Endocannabinoids or endocannabinoid-like compounds were assessed for their ability to modulate baseline permeability or OGD-induced hyperpermeability. Target sites of action were investigated using receptor antagonists and subsequently identified with real-time PCR. Anandamide (10 μM) and oleoylethanolamide (OEA, 10 μM) decreased BBB permeability (i.e. increased resistance). This was mediated by cannabinoid CB2 receptors, transient receptor potential vanilloid 1 (TRPV1) channels, calcitonin gene-regulated peptide (CGRP) receptor (anandamide only) and PPARα (OEA only). Application of OEA, palmitoylethanolamide (both PPARα mediated) or virodhamine (all 10 μM) decreased the OGD-induced increase in permeability during reperfusion. 2-Arachidonoyl glycerol, noladin ether and oleamide did not affect BBB permeability in normal or OGD conditions. N-arachidonoyl-dopamine increased permeability through a cytotoxic mechanism. PPARα and γ, CB1 receptors, TRPV1 channels and CGRP receptors were expressed in both cell types, but mRNA for CB2 receptors was only present in astrocytes. The endocannabinoids may play an important modulatory role in normal BBB physiology, and also afford protection to the BBB during ischaemic stroke, through a number of target sites. © 2015 The Authors. British Journal of Pharmacology published by John Wiley & Sons Ltd on behalf of The British Pharmacological Society.

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

    NARCIS (Netherlands)

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

    2014-01-01

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

  3. Data integration through brain atlasing: Human Brain Project tools and strategies.

    Science.gov (United States)

    Bjerke, Ingvild E; Øvsthus, Martin; Papp, Eszter A; Yates, Sharon C; Silvestri, Ludovico; Fiorilli, Julien; Pennartz, Cyriel M A; Pavone, Francesco S; Puchades, Maja A; Leergaard, Trygve B; Bjaalie, Jan G

    2018-04-01

    The Human Brain Project (HBP), an EU Flagship Initiative, is currently building an infrastructure that will allow integration of large amounts of heterogeneous neuroscience data. The ultimate goal of the project is to develop a unified multi-level understanding of the brain and its diseases, and beyond this to emulate the computational capabilities of the brain. Reference atlases of the brain are one of the key components in this infrastructure. Based on a new generation of three-dimensional (3D) reference atlases, new solutions for analyzing and integrating brain data are being developed. HBP will build services for spatial query and analysis of brain data comparable to current online services for geospatial data. The services will provide interactive access to a wide range of data types that have information about anatomical location tied to them. The 3D volumetric nature of the brain, however, introduces a new level of complexity that requires a range of tools for making use of and interacting with the atlases. With such new tools, neuroscience research groups will be able to connect their data to atlas space, share their data through online data systems, and search and find other relevant data through the same systems. This new approach partly replaces earlier attempts to organize research data based only on a set of semantic terminologies describing the brain and its subdivisions. Copyright © 2018 The Authors. Published by Elsevier Masson SAS.. All rights reserved.

  4. Phosphorylethanolamine content of human brain tumors.

    Science.gov (United States)

    Kinoshita, Y; Yokota, A; Koga, Y

    1994-12-01

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

  5. High Intensity Focused Ultrasound: A Novel Model of Mild Traumatic Brain Injury

    Science.gov (United States)

    2013-11-07

    Berry A, Capone F, Giorgio M, Pelicci P, de Kloet E, et al . 2007. Deletion of the life span determinant p66Shc prevents age-dependent increases in...in humans. Limitations to animal research must be recognized as well. Shanks et al (78) argue that animal models are not predictive of responses in...brain injury in animals to model mild traumatic brain injuries (mTBI) in humans. Wahab et al (95) reported that HIFU can impair neural axonal

  6. Quantitative Characterization of NOE and APT Effects in the Human Brain at 7 Tesla

    Science.gov (United States)

    Liu, Dapeng; Zhou, Jinyuan; Xue, Rong; Zuo, Zhentao; An, Jing; Wang, Danny JJ

    2012-01-01

    Purpose This study aimed to quantitatively investigate two main magnetization transfer (MT) effects at low B1: the nuclear Overhauser enhancement (NOE) and amide proton transfer (APT) in the human brain at 7 Tesla. Methods The MT effects in the human brain were characterized using a four-pool proton model, which consisted of bulk water, macromolecules, an amide group of mobile proteins and peptides, and NOE-related protons resonating upfield. The pool sizes, exchange rates, and relaxation times of these proton pools were investigated quantitatively by fitting, and the net signals of APT and NOE were simulated based on the fitted parameters. Results The results showed that the four-pool model fitted the experimental data quite well, and the NOE effects in human brain at 7 T had a broad spectrum distribution. The NOE effects peaked at a B1 of ~ 1 - 1.4 μT and were significantly stronger in the white matter than in the gray matter, corresponding to a pool-size ratio of approximately 2:1. Since the APT effect was relatively small compared to the NOE effects, MT asymmetry analysis yielded an NOE-dominated contrast in the healthy human brain in this range of B1. Conclusion These findings are important to identify the source of NOE effects and to quantify APT effects in human brain at 7 T. PMID:23238951

  7. Hemispheric Asymmetry of Human Brain Anatomical Network Revealed by Diffusion Tensor Tractography

    Directory of Open Access Journals (Sweden)

    Ni Shu

    2015-01-01

    Full Text Available The topological architecture of the cerebral anatomical network reflects the structural organization of the human brain. Recently, topological measures based on graph theory have provided new approaches for quantifying large-scale anatomical networks. However, few studies have investigated the hemispheric asymmetries of the human brain from the perspective of the network model, and little is known about the asymmetries of the connection patterns of brain regions, which may reflect the functional integration and interaction between different regions. Here, we utilized diffusion tensor imaging to construct binary anatomical networks for 72 right-handed healthy adult subjects. We established the existence of structural connections between any pair of the 90 cortical and subcortical regions using deterministic tractography. To investigate the hemispheric asymmetries of the brain, statistical analyses were performed to reveal the brain regions with significant differences between bilateral topological properties, such as degree of connectivity, characteristic path length, and betweenness centrality. Furthermore, local structural connections were also investigated to examine the local asymmetries of some specific white matter tracts. From the perspective of both the global and local connection patterns, we identified the brain regions with hemispheric asymmetries. Combined with the previous studies, we suggested that the topological asymmetries in the anatomical network may reflect the functional lateralization of the human brain.

  8. Study of intracranial pressure in human brain during transcranial magnetic stimulation.

    Science.gov (United States)

    Honrath, Marc; Sabouni, Abas

    2015-01-01

    This paper presents the results of cranial force in human brain due to electromagnetic pulse during transcranial magnetic stimulation. To model the force in a realistic brain, we used three dimensional magnetic resonance image of the 26 years old female subject. Simulation results show that during TMS procedure, there is a small force generated within the cranial tissue layers along with a torque value in different layers of brain tissues. The force depends on the magnitude of the magnetic field generated by the TMS coil.

  9. Measurement of human blood brain barrier integrity using 11C-inulin and positron emission tomography

    International Nuclear Information System (INIS)

    Hara, Toshihiko; Iio, Masaaki; Tsukiyama, Takashi

    1988-01-01

    Positron emission tomography (PET) using 11 C-inulin was demonstrated to be applicable to the clinical measurement of blood brain barrier permeability and cerebral interstitial fluid volume. Kinetic data were analyzed by application of a two compartment model, in which blood plasma and interstitial fluid spaces constitute the compartments. The blood activity contribution was subtracted from the PET count with the aid of the 11 CO inhalation technique. The values we estimated in a human brain were in agreement with the reported values obtained for animal brains by the use of 14 C-inulin. (orig.)

  10. An automatic rat brain extraction method based on a deformable surface model.

    Science.gov (United States)

    Li, Jiehua; Liu, Xiaofeng; Zhuo, Jiachen; Gullapalli, Rao P; Zara, Jason M

    2013-08-15

    The extraction of the brain from the skull in medical images is a necessary first step before image registration or segmentation. While pre-clinical MR imaging studies on small animals, such as rats, are increasing, fully automatic imaging processing techniques specific to small animal studies remain lacking. In this paper, we present an automatic rat brain extraction method, the Rat Brain Deformable model method (RBD), which adapts the popular human brain extraction tool (BET) through the incorporation of information on the brain geometry and MR image characteristics of the rat brain. The robustness of the method was demonstrated on T2-weighted MR images of 64 rats and compared with other brain extraction methods (BET, PCNN, PCNN-3D). The results demonstrate that RBD reliably extracts the rat brain with high accuracy (>92% volume overlap) and is robust against signal inhomogeneity in the images. Copyright © 2013 Elsevier B.V. All rights reserved.

  11. Measuring dopamine release in the human brain with PET

    Energy Technology Data Exchange (ETDEWEB)

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

    1995-12-01

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

  12. Pain-Related Brain Activity Evoked by Active and Dynamic Arm Movement: Delayed-Onset Muscle Soreness as a Promising Model for Studying Movement-Related Pain in Humans.

    Science.gov (United States)

    Matsuda, Yoichi; Kan, Shigeyuki; Uematsu, Hironobu; Shibata, Masahiko; Fujino, Yuji

    2015-08-01

    To demonstrate delayed-onset muscle soreness (DOMS) is a suitable model for the study of movement-evoked pain, we attempted to identify brain regions specifically involved in pain evoked by active and dynamic movement under DOMS condition. Twelve healthy volunteers DOMS was induced in the left upper-arm flexor muscles by an eccentric elbow contraction exercise. Movement-evoked pain in the affected muscles was evaluated just before (day 0) and after (days 1-7 and 30) the exercise using a visual analog scale. Subjects underwent functional magnetic resonance imaging scans while performing repeated elbow flexion on day 2 (DOMS condition) and day 30 (painless condition). We compared brain activity between the DOMS and painless conditions. Movement-evoked pain reached peak intensity on day 2 and disappeared by day 30 in all subjects. No subject felt pain at rest on either of these days. Contralateral primary motor cortex (M1), parietal operculum and bilateral presupplementary motor area (pre-SMA) showed greater activity during active and dynamic arm movement with DOMS than during the same movement without pain. There was no difference in activation of brain regions known collectively as the "pain matrix," except for the parietal operculum, between the two conditions. Active and dynamic movement with pain selectively evoked activation of M1, pre-SMA, and parietal operculum, as assessed using DOMS. Our results demonstrate that DOMS is a promising experimental model for the study of movement-evoked pain in humans. 2015 The Authors Pain Medicine published by Wiley Periodicals, Inc. on behalf of American Academy of Pain Medicine.

  13. Processing of Body Odor Signals by the Human Brain.

    Science.gov (United States)

    Pause, Bettina M

    2012-03-01

    Brain development in mammals has been proposed to be promoted by successful adaptations to the social complexity as well as to the social and non-social chemical environment. Therefore, the communication via chemosensory signals might have been and might still be a phylogenetically ancient communication channel transmitting evolutionary significant information. In humans, the neuronal underpinnings of the processing of social chemosignals have been investigated in relation to kin recognition, mate choice, the reproductive state and emotional contagion. These studies reveal that human chemosignals are probably not processed within olfactory brain areas but through neuronal relays responsible for the processing of social information. It is concluded that the processing of human social chemosignals resembles the processing of social signals originating from other modalities, except that human social chemosignals are usually communicated without the allocation of attentional resources, that is below the threshold of consciousness. Deviances in the processing of human social chemosignals might be related to the development and maintenance of mental disorders.

  14. Human Brain Expansion during Evolution Is Independent of Fire Control and Cooking.

    Science.gov (United States)

    Cornélio, Alianda M; de Bittencourt-Navarrete, Ruben E; de Bittencourt Brum, Ricardo; Queiroz, Claudio M; Costa, Marcos R

    2016-01-01

    What makes humans unique? This question has fascinated scientists and philosophers for centuries and it is still a matter of intense debate. Nowadays, human brain expansion during evolution has been acknowledged to explain our empowered cognitive capabilities. The drivers for such accelerated expansion remain, however, largely unknown. In this sense, studies have suggested that the cooking of food could be a pre-requisite for the expansion of brain size in early hominins. However, this appealing hypothesis is only supported by a mathematical model suggesting that the increasing number of neurons in the brain would constrain body size among primates due to a limited amount of calories obtained from diets. Here, we show, by using a similar mathematical model, that a tradeoff between body mass and the number of brain neurons imposed by dietary constraints during hominin evolution is unlikely. Instead, the predictable number of neurons in the hominin brain varies much more in function of foraging efficiency than body mass. We also review archeological data to show that the expansion of the brain volume in the hominin lineage is described by a linear function independent of evidence of fire control, and therefore, thermal processing of food does not account for this phenomenon. Finally, we report experiments in mice showing that thermal processing of meat does not increase its caloric availability in mice. Altogether, our data indicate that cooking is neither sufficient nor necessary to explain hominin brain expansion.

  15. Human brain expansion during evolution is independent of fire control and cooking

    Directory of Open Access Journals (Sweden)

    Alianda Maira Cornélio

    2016-04-01

    Full Text Available What makes humans unique? This question has fascinated scientists and philosophers for centuries and it is still a matter of intense debate. Nowadays, human brain expansion during evolution has been acknowledged to explain our empowered cognitive capabilities. The drivers for such accelerated expansion remain, however, largely unknown. In this sense, studies have suggested that the cooking of food could be a pre-requisite for the expansion of brain size in early hominins. However, this appealing hypothesis is only supported by a mathematical model suggesting that the increasing number of neurons in the brain would constrain body size among primates due to a limited amount of calories obtained from diets. Here, we show, by using a similar mathematical model, that a tradeoff between body mass and the number of brain neurons imposed by dietary constraints during hominin evolution is unlikely. Instead, the predictable number of neurons in the hominin brain varies much more in function of foraging efficiency than body mass. We also review archeological data to show that the expansion of the brain volume in the hominin lineage is described by a linear function independent of evidences of fire control, and therefore, thermal processing of food does not account for this phenomenon. Finally, we report experiments in mice showing that thermal processing of meat does not increase its caloric availability in mice. Altogether, our data indicate that cooking is neither sufficient nor necessary to explain hominin brain expansion.

  16. Gender development and the human brain.

    Science.gov (United States)

    Hines, Melissa

    2011-01-01

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

  17. Measuring and Reconstructing the Brain at the Synaptic Scale: Towards a Biofidelic Human Brain in silico

    OpenAIRE

    NeuroData; CE, Priebe; Burns, R.; RJ, Vogelstein

    2015-01-01

    Vogelstein JT, Priebe CE, Burns R, Vogelstein RJ, Lichtman J. Measuring and Reconstructing the Brain at the Synaptic Scale: Towards a Biofidelic Human Brain in silico. DARPA Neural Engineering, Science and Technology Forum, 2010

  18. Magnetic resonance elastography in normal human brain: preliminary study

    International Nuclear Information System (INIS)

    Xu Lei; Gao Peiyi; Lin Yan; Han Jiancheng; Xi Zhinong; Shen Hao

    2007-01-01

    Objective: To study the application of magnetic resonance elastography (MRE) in the human brain. Methods: An external force actuator was developed. The actuator was fixed to the head coil. During MRE scan, one side of the actuator was attached to the volunteers' head. Low frequency oscillation was produced by the actuator and generated shear waves propagating into brain tissue. The pulse sequence of MRE was designed. A modified gradient echo sequence was developed with motion sensitizing gradient (MSG) imposed along X, Y or Z direction. Cyclic displacement within brain tissue induced by shear waves caused a measurable phase shift in the received MR signal. From the measured phase shift, the displacement at each voxel could be calculated, and the shear waves within the brain were directly imaged. By adjusting the phase offset, the dynamic propagation of shear waves in a wave cycle was obtained. Phase images were processed with local frequency estimation (LFE) technique to obtain the elasticity images. Shear waves at 100 Hz, 150 Hz, and 200 Hz were applied. Results: The phase images of MRE directly imaged the propagating shear waves within the brain. The direction of the propagation was from surface of the brain to the center. The wavelength of shear waves varied with the change of actuating frequency. The change of wavelength of shear waves in gray and white matter of the brain was identified. The wavelength of shear waves in gray matter was shorter than that in white matter. The elasticity image of the brain revealed that the shear modulus of the white matter was higher than that of gray matter. Conclusion: The phase images of MRE can directly visualize the propagation of shear waves in the brain tissue. The elasticity image of the brain can demonstrate the change of elasticity between gray and white matter. (authors)

  19. Mechanistic Insights into Human Brain Impact Dynamics through Modal Analysis

    Science.gov (United States)

    Laksari, Kaveh; Kurt, Mehmet; Babaee, Hessam; Kleiven, Svein; Camarillo, David

    2018-03-01

    Although concussion is one of the greatest health challenges today, our physical understanding of the cause of injury is limited. In this Letter, we simulated football head impacts in a finite element model and extracted the most dominant modal behavior of the brain's deformation. We showed that the brain's deformation is most sensitive in low frequency regimes close to 30 Hz, and discovered that for most subconcussive head impacts, the dynamics of brain deformation is dominated by a single global mode. In this Letter, we show the existence of localized modes and multimodal behavior in the brain as a hyperviscoelastic medium. This dynamical phenomenon leads to strain concentration patterns, particularly in deep brain regions, which is consistent with reported concussion pathology.

  20. Evolution of the base of the brain in highly encephalized human species

    OpenAIRE

    Bastir, Markus; Rosas, Antonio; Gunz, Philipp; Peña-Melián, Ángel; Manzi, Giorgio; Harvati, Katerina; Kruszynski, Robert; Stringer, Chris; Hublin, Jean-Jacques

    2011-01-01

    The increase of brain size relative to body size-encephalization-is intimately linked with human evolution. However, two genetically different evolutionary lineages, Neanderthals and modern humans, have produced similarly large-brained human species. Thus, understanding human brain evolution should include research into specific cerebral reorganization, possibly reflected by brain shape changes. Here we exploit developmental integration between the brain and its underlying skeletal base to te...

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

    Science.gov (United States)

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

    2016-01-01

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

  2. Common genetic variants influence human subcortical brain structures.

    Science.gov (United States)

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

    2015-04-09

    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.

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

    Science.gov (United States)

    Chen, Bin; Moreland, John; Zhang, Jingyu

    2011-12-01

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

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

    Energy Technology Data Exchange (ETDEWEB)

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

    2011-09-27

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

  5. Mathematical logic in the human brain: syntax.

    Science.gov (United States)

    Friedrich, Roland; Friederici, Angela D

    2009-05-28

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

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

    CERN Multimedia

    CERN. Geneva

    2016-01-01

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

  7. Time resolved dosimetry of human brain exposed to low frequency pulsed magnetic fields

    Science.gov (United States)

    Paffi, Alessandra; Camera, Francesca; Lucano, Elena; Apollonio, Francesca; Liberti, Micaela

    2016-06-01

    An accurate dosimetry is a key issue to understanding brain stimulation and related interaction mechanisms with neuronal tissues at the basis of the increasing amount of literature revealing the effects on human brain induced by low-level, low frequency pulsed magnetic fields (PMFs). Most literature on brain dosimetry estimates the maximum E field value reached inside the tissue without considering its time pattern or tissue dispersivity. Nevertheless a time-resolved dosimetry, accounting for dispersive tissues behavior, becomes necessary considering that the threshold for an effect onset may vary depending on the pulse waveform and that tissues may filter the applied stimulatory fields altering the predicted stimulatory waveform’s size and shape. In this paper a time-resolved dosimetry has been applied on a realistic brain model exposed to the signal presented in Capone et al (2009 J. Neural Transm. 116 257-65), accounting for the broadband dispersivity of brain tissues up to several kHz, to accurately reconstruct electric field and current density waveforms inside different brain tissues. The results obtained by exposing the Duke’s brain model to this PMF signal show that the E peak in the brain is considerably underestimated if a simple monochromatic dosimetry is carried out at the pulse repetition frequency of 75 Hz.

  8. The human brain representation of odor identification.

    Science.gov (United States)

    Kjelvik, Grete; Evensmoen, Hallvard R; Brezova, Veronika; Håberg, Asta K

    2012-07-01

    Odor identification (OI) tests are increasingly used clinically as biomarkers for Alzheimer's disease and schizophrenia. The aim of this study was to directly compare the neuronal correlates to identified odors vs. nonidentified odors. Seventeen females with normal olfactory function underwent a functional magnetic resonance imaging (fMRI) experiment with postscanning assessment of spontaneous uncued OI. An event-related analysis was performed to compare within-subject activity to spontaneously identified vs. nonidentified odors at the whole brain level, and in anatomic and functional regions of interest (ROIs) in the medial temporal lobe (MTL). Parameter estimate values and blood oxygenated level-dependent (BOLD) signal curves for correctly identified and nonidentified odors were derived from functional ROIs in hippocampus, entorhinal, piriform, and orbitofrontal cortices. Number of activated voxels and max parameter estimate values were obtained from anatomic ROIs in the hippocampus and the entorhinal cortex. At the whole brain level the correct OI gave rise to increased activity in the left entorhinal cortex and secondary olfactory structures, including the orbitofrontal cortex. Increased activation was also observed in fusiform, primary visual, and auditory cortices, inferior frontal plus inferior temporal gyri. The anatomic MTL ROI analysis showed increased activation in the left entorhinal cortex, right hippocampus, and posterior parahippocampal gyri in correct OI. In the entorhinal cortex and hippocampus the BOLD signal increased specifically in response to identified odors and decreased for nonidentified odors. In orbitofrontal and piriform cortices both identified and nonidentified odors gave rise to an increased BOLD signal, but the response to identified odors was significantly greater than that for nonidentified odors. These results support a specific role for entorhinal cortex and hippocampus in OI, whereas piriform and orbitofrontal cortices are

  9. Genetic contributions to human brain morphology and intelligence

    DEFF Research Database (Denmark)

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

    2006-01-01

    Variation in gray matter (GM) and white matter (WM) volume of the adult human brain is primarily genetically determined. Moreover, total brain volume is positively correlated with general intelligence, and both share a common genetic origin. However, although genetic effects on morphology...... of specific GM areas in the brain have been studied, the heritability of focal WM is unknown. Similarly, it is unresolved whether there is a common genetic origin of focal GM and WM structures with intelligence. We explored the genetic influence on focal GM and WM densities in magnetic resonance brain images...... the focal GM and WM densities of each twin are correlated with the psychometric intelligence quotient of his/her cotwin. Genes influenced individual differences in left and right superior occipitofrontal fascicle (heritability up to 0.79 and 0.77), corpus callosum (0.82, 0.80), optic radiation (0.69, 0...

  10. Kisspeptin modulates sexual and emotional brain processing in humans.

    Science.gov (United States)

    Comninos, Alexander N; Wall, Matthew B; Demetriou, Lysia; Shah, Amar J; Clarke, Sophie A; Narayanaswamy, Shakunthala; Nesbitt, Alexander; Izzi-Engbeaya, Chioma; Prague, Julia K; Abbara, Ali; Ratnasabapathy, Risheka; Salem, Victoria; Nijher, Gurjinder M; Jayasena, Channa N; Tanner, Mark; Bassett, Paul; Mehta, Amrish; Rabiner, Eugenii A; Hönigsperger, Christoph; Silva, Meire Ribeiro; Brandtzaeg, Ole Kristian; Lundanes, Elsa; Wilson, Steven Ray; Brown, Rachel C; Thomas, Sarah A; Bloom, Stephen R; Dhillo, Waljit S

    2017-02-01

    Sex, emotion, and reproduction are fundamental and tightly entwined aspects of human behavior. At a population level in humans, both the desire for sexual stimulation and the desire to bond with a partner are important precursors to reproduction. However, the relationships between these processes are incompletely understood. The limbic brain system has key roles in sexual and emotional behaviors, and is a likely candidate system for the integration of behavior with the hormonal reproductive axis. We investigated the effects of kisspeptin, a recently identified key reproductive hormone, on limbic brain activity and behavior. Using a combination of functional neuroimaging and hormonal and psychometric analyses, we compared the effects of kisspeptin versus vehicle administration in 29 healthy heterosexual young men. We demonstrated that kisspeptin administration enhanced limbic brain activity specifically in response to sexual and couple-bonding stimuli. Furthermore, kisspeptin's enhancement of limbic brain structures correlated with psychometric measures of reward, drive, mood, and sexual aversion, providing functional significance. In addition, kisspeptin administration attenuated negative mood. Collectively, our data provide evidence of an undescribed role for kisspeptin in integrating sexual and emotional brain processing with reproduction in humans. These results have important implications for our understanding of reproductive biology and are highly relevant to the current pharmacological development of kisspeptin as a potential therapeutic agent for patients with common disorders of reproductive function. National Institute for Health Research (NIHR), Wellcome Trust (Ref 080268), and the Medical Research Council (MRC).

  11. Magnetic resonance elastography of the brain: A comparison between pigs and humans.

    Science.gov (United States)

    Weickenmeier, Johannes; Kurt, Mehmet; Ozkaya, Efe; Wintermark, Max; Pauly, Kim Butts; Kuhl, Ellen

    2018-01-01

    Magnetic resonance elastography holds promise as a non-invasive, easy-to-use, in vivo biomarker for neurodegenerative diseases. Throughout the past decade, pigs have gained increased popularity as large animal models for human neurodegeneration. However, the volume of a pig brain is an order of magnitude smaller than the human brain, its skull is 40% thicker, and its head is about twice as big. This raises the question to which extent established vibration devices, actuation frequencies, and analysis tools for humans translate to large animal studies in pigs. Here we explored the feasibility of using human brain magnetic resonance elastography to characterize the dynamic properties of the porcine brain. In contrast to humans, where vibration devices induce an anterior-posterior displacement recorded in transverse sections, the porcine anatomy requires a dorsal-ventral displacement recorded in coronal sections. Within these settings, we applied a wide range of actuation frequencies, from 40Hz to 90Hz, and recorded the storage and loss moduli for human and porcine brains. Strikingly, we found that optimal actuation frequencies for humans translate one-to-one to pigs and reliably generate shear waves for elastographic post-processing. In a direct comparison, human and porcine storage and loss moduli followed similar trends and increased with increasing frequency. When translating these frequency-dependent storage and loss moduli into the frequency-independent stiffnesses and viscosities of a standard linear solid model, we found human values of μ 1 =1.3kPa, μ 2 =2.1kPa, and η=0.025kPas and porcine values of μ 1 =2.0kPa, μ 2 =4.9kPa, and η=0.046kPas. These results suggest that living human brain is softer and less viscous than dead porcine brain. Our study compares, for the first time, magnetic resonance elastography in human and porcine brains, and paves the way towards systematic interspecies comparison studies and ex vivo validation of magnetic resonance

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

    Directory of Open Access Journals (Sweden)

    Yong He

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

  13. Using human brain activity to guide machine learning.

    Science.gov (United States)

    Fong, Ruth C; Scheirer, Walter J; Cox, David D

    2018-03-29

    Machine learning is a field of computer science that builds algorithms that learn. In many cases, machine learning algorithms are used to recreate a human ability like adding a caption to a photo, driving a car, or playing a game. While the human brain has long served as a source of inspiration for machine learning, little effort has been made to directly use data collected from working brains as a guide for machine learning algorithms. Here we demonstrate a new paradigm of "neurally-weighted" machine learning, which takes fMRI measurements of human brain activity from subjects viewing images, and infuses these data into the training process of an object recognition learning algorithm to make it more consistent with the human brain. After training, these neurally-weighted classifiers are able to classify images without requiring any additional neural data. We show that our neural-weighting approach can lead to large performance gains when used with traditional machine vision features, as well as to significant improvements with already high-performing convolutional neural network features. The effectiveness of this approach points to a path forward for a new class of hybrid machine learning algorithms which take both inspiration and direct constraints from neuronal data.

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

    NARCIS (Netherlands)

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

    2004-01-01

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

  15. Patient specific 3D visualisation of human brain | Baichoo ...

    African Journals Online (AJOL)

    University of Mauritius Research Journal. Journal Home · ABOUT THIS JOURNAL · Advanced Search · Current Issue · Archives · Journal Home > Vol 15, No 1 (2009) >. Log in or Register to get access to full text downloads. Username, Password, Remember me, or Register. Patient specific 3D visualisation of human brain.

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

    Indian Academy of Sciences (India)

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

  17. Neural plasticity in human brain connectivity: the effects of long term deep brain stimulation of the subthalamic nucleus in Parkinson's disease.

    Science.gov (United States)

    van Hartevelt, Tim J; Cabral, Joana; Deco, Gustavo; Møller, Arne; Green, Alexander L; Aziz, Tipu Z; Kringelbach, Morten L

    2014-01-01

    Positive clinical outcomes are now well established for deep brain stimulation, but little is known about the effects of long-term deep brain stimulation on brain structural and functional connectivity. Here, we used the rare opportunity to acquire pre- and postoperative diffusion tensor imaging in a patient undergoing deep brain stimulation in bilateral subthalamic nuclei for Parkinson's Disease. This allowed us to analyse the differences in structural connectivity before and after deep brain stimulation. Further, a computational model of spontaneous brain activity was used to estimate the changes in functional connectivity arising from the specific changes in structural connectivity. We found significant localised structural changes as a result of long-term deep brain stimulation. These changes were found in sensory-motor, prefrontal/limbic, and olfactory brain regions which are known to be affected in Parkinson's Disease. The nature of these changes was an increase of nodal efficiency in most areas and a decrease of nodal efficiency in the precentral sensory-motor area. Importantly, the computational model clearly shows the impact of deep brain stimulation-induced structural alterations on functional brain changes, which is to shift the neural dynamics back towards a healthy regime. The results demonstrate that deep brain stimulation in Parkinson's Disease leads to a topological reorganisation towards healthy bifurcation of the functional networks measured in controls, which suggests a potential neural mechanism for the alleviation of symptoms. The findings suggest that long-term deep brain stimulation has not only restorative effects on the structural connectivity, but also affects the functional connectivity at a global level. Overall, our results support causal changes in human neural plasticity after long-term deep brain stimulation and may help to identify the underlying mechanisms of deep brain stimulation.

  18. Visualization of specific binding sites of benzodiazepine in human brain

    International Nuclear Information System (INIS)

    Shinotoh, H.; Yamasaki, T.; Inoue, O.; Itoh, T.; Suzuki, K.; Hashimoto, K.; Tateno, Y.; Ikehira, H.

    1986-01-01

    Using 11C-labeled Ro15-1788 and positron emission tomography, studies of benzodiazepine binding sites in the human brain were performed on four normal volunteers. Rapid and high accumulation of 11C activity was observed in the brain after i.v. injection of [11C]Ro15-1788, the maximum of which was within 12 min. Initial distribution of 11C activity in the brain was similar to the distribution of the normal cerebral blood flow. Ten minutes after injection, however, a high uptake of 11C activity was observed in the cerebral cortex and moderate uptake was seen in the cerebellar cortex, the basal ganglia, and the thalamus. The accumulation of 11C activity was low in the brain stem. This distribution of 11C activity was approximately parallel to the known distribution of benzodiazepine receptors. Saturation experiments were performed on four volunteers with oral administration of 0.3-1.8 mg/kg of cold Ro15-1788 prior to injection. Initial distribution of 11C activity following injection peaked within 2 min and then the accumulation of 11C activity decreased rapidly and remarkably throughout the brain. The results indicated that [11C] Ro15-1788 associates and dissociates to specific and nonspecific binding sites rapidly and has a high ratio of specific receptor binding to nonspecific binding in vivo. Carbon-11 Ro15-1788 is a suitable radioligand for the study of benzodiazepine receptors in vivo in humans

  19. Direct Electrical Stimulation in the Human Brain Disrupts Melody Processing.

    Science.gov (United States)

    Garcea, Frank E; Chernoff, Benjamin L; Diamond, Bram; Lewis, Wesley; Sims, Maxwell H; Tomlinson, Samuel B; Teghipco, Alexander; Belkhir, Raouf; Gannon, Sarah B; Erickson, Steve; Smith, Susan O; Stone, Jonathan; Liu, Lynn; Tollefson, Trenton; Langfitt, John; Marvin, Elizabeth; Pilcher, Webster H; Mahon, Bradford Z

    2017-09-11

    Prior research using functional magnetic resonance imaging (fMRI) [1-4] and behavioral studies of patients with acquired or congenital amusia [5-8] suggest that the right posterior superior temporal gyrus (STG) in the human brain is specialized for aspects of music processing (for review, see [9-12]). Intracranial electrical brain stimulation in awake neurosurgery patients is a powerful means to determine the computations supported by specific brain regions and networks [13-21] because it provides reversible causal evidence with high spatial resolution (for review, see [22, 23]). Prior intracranial stimulation or cortical cooling studies have investigated musical abilities related to reading music scores [13, 14] and singing familiar songs [24, 25]. However, individuals with amusia (congenitally, or from a brain injury) have difficulty humming melodies but can be spared for singing familiar songs with familiar lyrics [26]. Here we report a detailed study of a musician with a low-grade tumor in the right temporal lobe. Functional MRI was used pre-operatively to localize music processing to the right STG, and the patient subsequently underwent awake intraoperative mapping using direct electrical stimulation during a melody repetition task. Stimulation of the right STG induced "music arrest" and errors in pitch but did not affect language processing. These findings provide causal evidence for the functional segregation of music and language processing in the human brain and confirm a specific role of the right STG in melody processing. VIDEO ABSTRACT. Copyright © 2017 Elsevier Ltd. All rights reserved.

  20. Common genetic variants influence human subcortical brain structures

    Science.gov (United States)

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

    2015-01-01

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

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

    Science.gov (United States)

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

    2011-01-01

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

  2. Topological isomorphisms of human brain and financial market networks

    Directory of Open Access Journals (Sweden)

    Petra E Vértes

    2011-09-01

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

  3. Analysis of Mammalian Septin Expression in Human Malignant Brain Tumors

    Directory of Open Access Journals (Sweden)

    Dong-Seok Kim

    2004-03-01

    Full Text Available Septins are a highly conserved subfamily of GTPases that play an important role in the process of cytokinesis. To increase our understanding of the expression and localization of the different mammalian septins in human brain tumors, we used antibodies against septins 2, 3, 4, 5, 6, 7, 9, and 11 in immunofluorescence and Western blot analyses of astrocytomas and medulloblastomas. We then characterized the expression and subcellular distribution of the SEPT2 protein in aphidicolin-synchronized U373 MG astrocytoma cells by immunofluorescence and fluorescenceactivated cell sorter analysis. To determine the role of SEPT2 in astrocytoma cytokinesis, we inducibly expressed a dominant-negative (DN SEPT2 mutant in U373 MG astrocytoma cells. We show variable levels and expression patterns of the different septins in brain tissue, brain tumor specimens, and human brain tumor cell lines. SEPT2 was abundantly expressed in all brain tumor samples and cell lines studied. SEPT3 was expressed in medulloblastoma specimens and cell lines, but not in astrocytoma specimens or cell lines. SEPT2 expression was cell cycle-related, with maximal levels in G2-M. Immunocytochemical analysis showed endogenous levels of the different septins within the perinuclear and peripheral cytoplasmic regions. In mitosis, SEPT2 was concentrated at the cleavage furrow. By immunocytochemistry and flow cytometry, we show that a DN SEPT2 mutant inhibits the completion of cell division and results in the accumulation of multinucleated cells. These results suggest that septins are variably expressed in human brain tumors. Stable expression of the DN SEPT2 mutant leads to a G2-M cell cycle block in astrocytoma cells.

  4. The role of human endogenous retroviruses in brain development and function.

    Science.gov (United States)

    Mortelmans, Kristien; Wang-Johanning, Feng; Johanning, Gary L

    2016-01-01

    Endogenous retroviral sequences are spread throughout the genome of all humans, and make up about 8% of the genome. Despite their prevalence, the function of human endogenous retroviruses (HERVs) in humans is largely unknown. In this review we focus on the brain, and evaluate studies in animal models that address mechanisms of endogenous retrovirus activation in the brain and central nervous system (CNS). One such study in mice found that TRIM28, a protein critical for mouse early development, regulates transcription and silencing of endogenous retroviruses in neural progenitor cells. Another intriguing finding in human brain cells and mouse models was that endogenous retrovirus HERV-K appears to be protective against neurotoxins. We also report on studies that associate HERVs with human diseases of the brain and CNS. There is little doubt of an association between HERVs and a number of CNS diseases. However, a cause and effect relationship between HERVs and these diseases has not yet been established. © 2016 APMIS. Published by John Wiley & Sons Ltd.

  5. Deep Neural Networks: A New Framework for Modeling Biological Vision and Brain Information Processing.

    Science.gov (United States)

    Kriegeskorte, Nikolaus

    2015-11-24

    Recent advances in neural network modeling have enabled major strides in computer vision and other artificial intelligence applications. Human-level visual recognition abilities are coming within reach of artificial systems. Artificial neural networks are inspired by the brain, and their computations could be implemented in biological neurons. Convolutional feedforward networks, which now dominate computer vision, take further inspiration from the architecture of the primate visual hierarchy. However, the current models are designed with engineering goals, not to model brain computations. Nevertheless, initial studies comparing internal representations between these models and primate brains find surprisingly similar representational spaces. With human-level performance no longer out of reach, we are entering an exciting new era, in which we will be able to build biologically faithful feedforward and recurrent computational models of how biological brains perform high-level feats of intelligence, including vision.

  6. On a Quantum Model of Brain Activities

    Science.gov (United States)

    Fichtner, K.-H.; Fichtner, L.; Freudenberg, W.; Ohya, M.

    2010-01-01

    One of the main activities of the brain is the recognition of signals. A first attempt to explain the process of recognition in terms of quantum statistics was given in [6]. Subsequently, details of the mathematical model were presented in a (still incomplete) series of papers (cf. [7, 2, 5, 10]). In the present note we want to give a general view of the principal ideas of this approach. We will introduce the basic spaces and justify the choice of spaces and operations. Further, we bring the model face to face with basic postulates any statistical model of the recognition process should fulfill. These postulates are in accordance with the opinion widely accepted in psychology and neurology.

  7. Automated regional behavioral analysis for human brain images.

    Science.gov (United States)

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

    2012-01-01

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

  8. Brain lactate metabolism in humans with subarachnoid hemorrhage.

    Science.gov (United States)

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

    2012-05-01

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

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

    DEFF Research Database (Denmark)

    Catani, Marco; Robertsson, Naianna; Beyh, Ahmad

    2017-01-01

    The parietal lobe has a unique place in the human brain. Anatomically, it is at the crossroad between the frontal, occipital, and temporal lobes, thus providing a middle ground for multimodal sensory integration. Functionally, it supports higher cognitive functions that are characteristic...... intralobar parietal tracts in twenty-one datasets acquired in vivo from healthy human subjects and eleven ex vivo datasets from five vervet and six macaque monkeys. Three regions of interest (postcentral gyrus, superior parietal lobule and inferior parietal lobule) were used to identify the tracts. Surface...... is a vertical pathway between the superior and inferior parietal lobules. This tract can be divided into an anterior (supramarginal gyrus) and a posterior (angular gyrus) component in both humans and monkey brains. The second prominent intraparietal tract connects the postcentral gyrus to both supramarginal...

  10. Xanthine oxidase activity regulates human embryonic brain cells growth

    Directory of Open Access Journals (Sweden)

    Kevorkian G. A.

    2011-10-01

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

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

    Science.gov (United States)

    Nees, Frauke

    2015-09-01

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

  12. Mapping the calcitonin receptor in human brain stem

    DEFF Research Database (Denmark)

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

    2016-01-01

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

  13. Dyadic Brain - A Biological Model for Deliberative Inference

    Directory of Open Access Journals (Sweden)

    Iliyan Ivanov

    2017-10-01

    Full Text Available The human brain is arguably the most complex information processing system. It operates by acquiring data from the environment, recognizing patterns of events’ occurrence, anticipating their re-occurrence and in turn generating appropriate behavioral responses. Through the lenses of the free-energy principle any self-organizing system that is at equilibrium with its environment must minimize its free energy either by manipulating the environmental sensory input or by manipulating its internal states thus altering the recognition density of the outside stimuli. However, several sets of challenges interfere with the human brain's ability to learn and adapt in such a theoretically optimal fashion. These may include, and are not limited to, functional inconsistencies related to attention and memory processes, the functions of “fast” and “slow” thinking and responding, and the ability of emotional states to generate unintended behavioral outcomes that are less adaptive or inappropriate. This paper will review literature on the subject of how ideal learning viewed from the free-energy principle perspective may be affected by the above mentioned limitations and will suggest a model of information processing that may have developed as a way of overcoming these challenges. This neurobiological model stipulates that a neuronal network is formed in response to environmental input and is paralleled by at least one and possibly multiple networks that activate intrinsically and represent “virtual responses” to a situation that demands a behavioral response. This model accounts for how the brain generates a multiplicity of potential behavioral responses and may “choose” the one that seems most appropriate and also explains the uncanny ability of humans to socialize and collaborate. Implications for understanding humans’ ability to learn from others, deliberate on opposing constructs and access and utilize information outside of individual

  14. Modeling cognition and disease using human glial chimeric mice

    DEFF Research Database (Denmark)

    Goldman, Steven A.; Nedergaard, Maiken; Windrem, Martha S.

    2015-01-01

    As new methods for producing and isolating human glial progenitor cells (hGPCs) have been developed, the disorders of myelin have become especially compelling targets for cell-based therapy. Yet as animal modeling of glial progenitor cell-based therapies has progressed, it has become clear......, oligodendrocytes as well. As a result, the recipient brains may become inexorably humanized with regards to their resident glial populations, yielding human glial chimeric mouse brains. These brains provide us a fundamentally new tool by which to assess the species-specific attributes of glia in modulating human...... for studying the human-specific contributions of glia to psychopathology, as well as to higher cognition. As such, the assessment of human glial chimeric mice may provide us new insight into the species-specific contributions of glia to human cognitive evolution, as well as to the pathogenesis of human...

  15. Neocortical glial cell numbers in human brains

    DEFF Research Database (Denmark)

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

    2008-01-01

    and neurons and counting were done in each of the four lobes. The study showed that the different subpopulations of glial cells behave differently as a function of age; the number of oligodendrocytes showed a significant 27% decrease over adult life and a strong correlation to the total number of neurons...... while the total astrocyte number is constant through life; finally males have a 28% higher number of neocortical glial cells and a 19% higher neocortical neuron number than females. The overall total number of neocortical neurons and glial cells was 49.3 billion in females and 65.2 billion in males......, a difference of 24% with a high biological variance. These numbers can serve as reference values in quantitative studies of the human neocortex. (C) 2007 Elsevier Inc. All rights reserved Udgivelsesdato: 2008/11...

  16. What can we learn about brain donors? Use of clinical information in human postmortem brain research.

    Science.gov (United States)

    Sullivan, Kathleen; Pantazopoulos, Harry; Liebson, Elizabeth; Woo, T-U W; Baldessarini, Ross J; Hedreen, John; Berretta, Sabina

    2018-01-01

    Postmortem studies on the human brain reside at the core of investigations on neurologic and psychiatric disorders. Ground-breaking advances continue to be made on the pathologic basis of many of these disorders, at molecular, cellular, and neural connectivity levels. In parallel, there is increasing emphasis on improving methods to extract relevant demographic and clinical information about brain donors and, importantly, translate it into measures that can reliably and effectively be incorporated in the design and data analysis of postmortem human investigations. Here, we review the main source of information typically available to brain banks and provide examples on how this information can be processed. In particular, we discuss approaches to establish primary and secondary diagnoses, estimate exposure to therapeutic treatment and substance abuse, assess agonal status, and use time of death as a proxy in investigations on circadian rhythms. Although far from exhaustive, these considerations are intended as a contribution to ongoing efforts from tissue banks and investigators aimed at establishing robust, well-validated methods for collecting and standardizing information about brain donors, further strengthening the scientific rigor of human postmortem studies. Copyright © 2018 Elsevier B.V. All rights reserved.

  17. Progress and challenges in probing the human brain.

    Science.gov (United States)

    Poldrack, Russell A; Farah, Martha J

    2015-10-15

    Perhaps one of the greatest scientific challenges is to understand the human brain. Here we review current methods in human neuroscience, highlighting the ways that they have been used to study the neural bases of the human mind. We begin with a consideration of different levels of description relevant to human neuroscience, from molecules to large-scale networks, and then review the methods that probe these levels and the ability of these methods to test hypotheses about causal mechanisms. Functional MRI is considered in particular detail, as it has been responsible for much of the recent growth of human neuroscience research. We briefly review its inferential strengths and weaknesses and present examples of new analytic approaches that allow inferences beyond simple localization of psychological processes. Finally, we review the prospects for real-world applications and new scientific challenges for human neuroscience.

  18. New perspectives in EEG/MEG brain mapping and PET/fMRI neuroimaging of human pain.

    Science.gov (United States)

    Chen, A C

    2001-10-01

    With the maturation of EEG/MEG brain mapping and PET/fMRI neuroimaging in the 1990s, greater understanding of pain processing in the brain now elucidates and may even challenge the classical theory of pain mechanisms. This review scans across the cultural diversity of pain expression and modulation in man. It outlines the difficulties in defining and studying human pain. It then focuses on methods of studying the brain in experimental and clinical pain, the cohesive results of brain mapping and neuroimaging of noxious perception, the implication of pain research in understanding human consciousness and the relevance to clinical care as well as to the basic science of human psychophysiology. Non-invasive brain studies in man start to unveil the age-old puzzles of pain-illusion, hypnosis and placebo in pain modulation. The neurophysiological and neurohemodynamic brain measures of experimental pain can now largely satisfy the psychophysiologist's dream, unimaginable only a few years ago, of modelling the body-brain, brain-mind, mind-matter duality in an inter-linking 3-P triad: physics (stimulus energy); physiology (brain activities); and psyche (perception). For neuropsychophysiology greater challenges lie ahead: (a) how to integrate a cohesive theory of human pain in the brain; (b) what levels of analyses are necessary and sufficient; (c) what constitutes the structural organisation of the pain matrix; (d) what are the modes of processing among and across the sites of these structures; and (e) how can neural computation of these processes in the brain be carried out? We may envision that modular identification and delineation of the arousal-attention, emotion-motivation and perception-cognition neural networks of pain processing in the brain will also lead to deeper understanding of the human mind. Two foreseeable impacts on clinical sciences and basic theories from brain mapping/neuroimaging are the plausible central origin in persistent pain and integration of

  19. Attenuation correction for the large non-human primate brain imaging using microPET

    Science.gov (United States)

    Naidoo-Variawa, S.; Lehnert, W.; Kassiou, M.; Banati, R.; Meikle, S. R.

    2010-04-01

    Assessment of the biodistribution and pharmacokinetics of radiopharmaceuticals in vivo is often performed on animal models of human disease prior to their use in humans. The baboon brain is physiologically and neuro-anatomically similar to the human brain and is therefore a suitable model for evaluating novel CNS radioligands. We previously demonstrated the feasibility of performing baboon brain imaging on a dedicated small animal PET scanner provided that the data are accurately corrected for degrading physical effects such as photon attenuation in the body. In this study, we investigated factors affecting the accuracy and reliability of alternative attenuation correction strategies when imaging the brain of a large non-human primate (papio hamadryas) using the microPET Focus 220 animal scanner. For measured attenuation correction, the best bias versus noise performance was achieved using a 57Co transmission point source with a 4% energy window. The optimal energy window for a 68Ge transmission source operating in singles acquisition mode was 20%, independent of the source strength, providing bias-noise performance almost as good as for 57Co. For both transmission sources, doubling the acquisition time had minimal impact on the bias-noise trade-off for corrected emission images, despite observable improvements in reconstructed attenuation values. In a [18F]FDG brain scan of a female baboon, both measured attenuation correction strategies achieved good results and similar SNR, while segmented attenuation correction (based on uncorrected emission images) resulted in appreciable regional bias in deep grey matter structures and the skull. We conclude that measured attenuation correction using a single pass 57Co (4% energy window) or 68Ge (20% window) transmission scan achieves an excellent trade-off between bias and propagation of noise when imaging the large non-human primate brain with a microPET scanner.

  20. Attenuation correction for the large non-human primate brain imaging using microPET

    International Nuclear Information System (INIS)

    Naidoo-Variawa, S; Lehnert, W; Kassiou, M; Banati, R; Meikle, S R

    2010-01-01

    Assessment of the biodistribution and pharmacokinetics of radiopharmaceuticals in vivo is often performed on animal models of human disease prior to their use in humans. The baboon brain is physiologically and neuro-anatomically similar to the human brain and is therefore a suitable model for evaluating novel CNS radioligands. We previously demonstrated the feasibility of performing baboon brain imaging on a dedicated small animal PET scanner provided that the data are accurately corrected for degrading physical effects such as photon attenuation in the body. In this study, we investigated factors affecting the accuracy and reliability of alternative attenuation correction strategies when imaging the brain of a large non-human primate (papio hamadryas) using the microPET Focus 220 animal scanner. For measured attenuation correction, the best bias versus noise performance was achieved using a 57 Co transmission point source with a 4% energy window. The optimal energy window for a 68 Ge transmission source operating in singles acquisition mode was 20%, independent of the source strength, providing bias-noise performance almost as good as for 57 Co. For both transmission sources, doubling the acquisition time had minimal impact on the bias-noise trade-off for corrected emission images, despite observable improvements in reconstructed attenuation values. In a [ 18 F]FDG brain scan of a female baboon, both measured attenuation correction strategies achieved good results and similar SNR, while segmented attenuation correction (based on uncorrected emission images) resulted in appreciable regional bias in deep grey matter structures and the skull. We conclude that measured attenuation correction using a single pass 57 Co (4% energy window) or 68 Ge (20% window) transmission scan achieves an excellent trade-off between bias and propagation of noise when imaging the large non-human primate brain with a microPET scanner.

  1. A human-specific de novo protein-coding gene associated with human brain functions.

    Directory of Open Access Journals (Sweden)

    Chuan-Yun Li

    2010-03-01

    Full Text Available To understand whether any human-specific new genes may be associated with human brain functions, we computationally screened the genetic vulnerable factors identified through Genome-Wide Association Studies and linkage analyses of nicotine addiction and found one human-specific de novo protein-coding gene, FLJ33706 (alternative gene symbol C20orf203. Cross-species analysis revealed interesting evolutionary paths of how this gene had originated from noncoding DNA sequences: insertion of repeat elements especially Alu contributed to the formation of the first coding exon and six standard splice junctions on the branch leading to humans and chimpanzees, and two subsequent substitutions in the human lineage escaped two stop codons and created an open reading frame of 194 amino acids. We experimentally verified FLJ33706's mRNA and protein expression in the brain. Real-Time PCR in multiple tissues demonstrated that FLJ33706 was most abundantly expressed in brain. Human polymorphism data suggested that FLJ33706 encodes a protein under purifying selection. A specifically designed antibody detected its protein expression across human cortex, cerebellum and midbrain. Immunohistochemistry study in normal human brain cortex revealed the localization of FLJ33706 protein in neurons. Elevated expressions of FLJ33706 were detected in Alzheimer's brain samples, suggesting the role of this novel gene in human-specific pathogenesis of Alzheimer's disease. FLJ33706 provided the strongest evidence so far that human-specific de novo genes can have protein-coding potential and differential protein expression, and be involved in human brain functions.

  2. Avian Models for Human Cognitive Neuroscience: A Proposal.

    Science.gov (United States)

    Clayton, Nicola S; Emery, Nathan J

    2015-06-17

    Research on avian cognitive neuroscience over the past two decades has revealed the avian brain to be a better model for understanding human cognition than previously thought, despite differences in the neuroarchitecture of avian and mammalian brains. The brain, behavior, and cognition of songbirds have provided an excellent model of human cognition in one domain, namely learning human language and the production of speech. There are other important behavioral candidates of avian cognition, however, notably the capacity of corvids to remember the past and plan for the future, as well as their ability to think about another's perspective, and physical reasoning. We review this work and assess the evidence that the corvid brain can support such a cognitive architecture. We propose potential applications of these behavioral paradigms for cognitive neuroscience, including recent work on single-cell recordings and neuroimaging in corvids. Finally, we discuss their impact on understanding human developmental cognition. Copyright © 2015 Elsevier Inc. All rights reserved.

  3. Exclusive neuronal expression of SUCLA2 in the human brain

    DEFF Research Database (Denmark)

    Dobolyi, Arpád; Ostergaard, Elsebet; Bagó, Attila G

    2015-01-01

    SUCLA2 encodes the ATP-forming β subunit (A-SUCL-β) of succinyl-CoA ligase, an enzyme of the citric acid cycle. Mutations in SUCLA2 lead to a mitochondrial disorder manifesting as encephalomyopathy with dystonia, deafness and lesions in the basal ganglia. Despite the distinct brain pathology......-SUCL-β) encoded by SUCLG2, or in situ hybridization histochemistry for SUCLG2 mRNA could not be demonstrated in either neurons or astrocytes. Western blotting of post mortem brain samples revealed minor G-SUCL-β immunoreactivity that was, however, not upregulated in samples obtained from diabetic versus non......-diabetic patients, as has been described for murine brain. Our work establishes that SUCLA2 is expressed exclusively in neurons in the human cerebral cortex....

  4. Brain-Computer Interfaces Revolutionizing Human-Computer Interaction

    CERN Document Server

    Graimann, Bernhard; Allison, Brendan

    2010-01-01

    A brain-computer interface (BCI) establishes a direct output channel between the human brain and external devices. BCIs infer user intent via direct measures of brain activity and thus enable communication and control without movement. This book, authored by experts in the field, provides an accessible introduction to the neurophysiological and signal-processing background required for BCI, presents state-of-the-art non-invasive and invasive approaches, gives an overview of current hardware and software solutions, and reviews the most interesting as well as new, emerging BCI applications. The book is intended not only for students and young researchers, but also for newcomers and other readers from diverse backgrounds keen to learn about this vital scientific endeavour.

  5. Endurance training enhances BDNF release from the human brain

    DEFF Research Database (Denmark)

    Seifert, Thomas; Brassard, Patrice; Wissenberg, Mads

    2010-01-01

    The circulating level of brain-derived neurotrophic factor (BDNF) is reduced in patients with major depression and type-2 diabetes. Because acute exercise increases BDNF production in the hippocampus and cerebral cortex, we hypothesized that endurance training would enhance the release of BDNF from...... the human brain as detected from arterial and internal jugular venous blood samples. In a randomized controlled study, 12 healthy sedentary males carried out 3 mo of endurance training (n = 7) or served as controls (n = 5). Before and after the intervention, blood samples were obtained at rest and during...... exercise. At baseline, the training group (58 + or - 106 ng x 100 g(-1) x min(-1), means + or - SD) and the control group (12 + or - 17 ng x 100 g(-1) x min(-1)) had a similar release of BDNF from the brain at rest. Three months of endurance training enhanced the resting release of BDNF to 206 + or - 108...

  6. Intraoperative Functional Ultrasound Imaging of Human Brain Activity.

    Science.gov (United States)

    Imbault, Marion; Chauvet, Dorian; Gennisson, Jean-Luc; Capelle, Laurent; Tanter, Mickael

    2017-08-04

    The functional mapping of brain activity is essential to perform optimal glioma surgery and to minimize the risk of postoperative deficits. We introduce a new, portable neuroimaging modality of the human brain based on functional ultrasound (fUS) for deep functional cortical mapping. Using plane-wave transmissions at an ultrafast frame rate (1 kHz), fUS is performed during surgery to measure transient changes in cerebral blood volume with a high spatiotemporal resolution (250 µm, 1 ms). fUS identifies, maps and differentiates regions of brain activation during task-evoked cortical responses within the depth of a sulcus in both awake and anaesthetized patients.

  7. Is the social brain theory applicable to human individual differences? Relationship between sociability personality dimension and brain size.

    Science.gov (United States)

    Horváth, Klára; Martos, János; Mihalik, Béla; Bódizs, Róbert

    2011-06-17

    Our study intends to examine whether the social brain theory is applicable to human individual differences. According to the social brain theory primates have larger brains as it could be expected from their body sizes due to the adaptation to a more complex social life. Regarding humans there were few studies about the relationship between theory of mind and frontal and temporal brain lobes. We hypothesized that these brain lobes, as well as the whole cerebrum and neocortex are in connection with the Sociability personality dimension that is associated with individuals' social lives. Our findings support this hypothesis as Sociability correlated positively with the examined brain structures if we control the effects of body size differences and age. These results suggest that the social brain theory can be extended to human interindividual differences and they have some implications to personality psychology too.

  8. Is the Social Brain Theory Applicable to Human Individual Differences? Relationship between Sociability Personality Dimension and Brain Size

    Directory of Open Access Journals (Sweden)

    Klára Horváth

    2011-04-01

    Full Text Available Our study intends to examine whether the social brain theory is applicable to human individual differences. According to the social brain theory primates have larger brains as it could be expected from their body sizes due to the adaptation to a more complex social life. Regarding humans there were few studies about the relationship between theory of mind and frontal and temporal brain lobes. We hypothesized that these brain lobes, as well as the whole cerebrum and neocortex are in connection with the Sociability personality dimension that is associated with individuals' social lives. Our findings support this hypothesis as Sociability correlated positively with the examined brain structures if we control the effects of body size differences and age. These results suggest that the social brain theory can be extended to human interindividual differences and they have some implications to personality psychology too.

  9. Sigma and opioid receptors in human brain tumors

    Energy Technology Data Exchange (ETDEWEB)

    Thomas, G.E.; Szuecs, M.; Mamone, J.Y.; Bem, W.T.; Rush, M.D.; Johnson, F.E.; Coscia, C.J. (St. Louis Univ. School of Medicine, MO (USA))

    1990-01-01

    Human brain tumors and nude mouse-borne human neuroblastomas and gliomas were analyzed for sigma and opioid receptor content. Sigma binding was assessed using ({sup 3}H) 1, 3-di-o-tolylguanidine (DTG), whereas opioid receptor subtypes were measured with tritiated forms of the following: {mu}, (D-ala{sup 2}, mePhe{sup 4}, gly-ol{sup 5}) enkephalin (DAMGE); {kappa}, ethylketocyclazocine (EKC) or U69,593; {delta}, (D-pen{sup 2}, D-pen{sup 5}) enkephalin (DPDPE) or (D-ala{sup 2}, D-leu{sup 5}) enkephalin (DADLE) with {mu} suppressor present. Binding parameters were estimated by homologous displacement assays followed by analysis using the LIGAND program. Sigma binding was detected in 15 of 16 tumors examined with very high levels found in a brain metastasis from an adenocarcinoma of lung and a human neuroblastoma (SK-N-MC) passaged in nude mice. {kappa} opioid receptor binding was detected in 4 of 4 glioblastoma multiforme specimens and 2 of 2 human astrocytoma cell lines tested but not in the other brain tumors analyzed.

  10. Ad cerebrum per scientia: Ira Hirsh, psychoacoustics, and new approaches to understanding the human brain

    Science.gov (United States)

    Lauter, Judith

    2002-05-01

    As Research Director of CID, Ira emphasized the importance of combining information from biology with rigorous studies of behavior, such as psychophysics, to better understand how the brain and body accomplish the goals of everyday life. In line with this philosophy, my doctoral dissertation sought to explain brain functional asymmetries (studied with dichotic listening) in terms of the physical dimensions of a library of test sounds designed to represent a speech-music continuum. Results highlighted individual differences plus similarities in terms of patterns of relative ear advantages, suggesting an organizational basis for brain asymmetries depending on physical dimensions of stimulus and gesture with analogs in auditory, visual, somatosensory, and motor systems. My subsequent work has employed a number of noninvasive methods (OAEs, EPs, qEEG, PET, MRI) to explore the neurobiological bases of individual differences in general and functional asymmetries in particular. This research has led to (1) the AXS test battery for assessing the neurobiology of human sensory-motor function; (2) the handshaking model of brain function, describing dynamic relations along all three body/brain axes; (3) the four-domain EPIC model of functional asymmetries; and (4) the trimodal brain, a new model of individual differences based on psychoimmunoneuroendocrinology.

  11. Testosterone affects language areas of the adult human brain.

    Science.gov (United States)

    Hahn, Andreas; Kranz, Georg S; Sladky, Ronald; Kaufmann, Ulrike; Ganger, Sebastian; Hummer, Allan; Seiger, Rene; Spies, Marie; Vanicek, Thomas; Winkler, Dietmar; Kasper, Siegfried; Windischberger, Christian; Swaab, Dick F; Lanzenberger, Rupert

    2016-05-01

    Although the sex steroid hormone testosterone is integrally involved in the development of language processing, ethical considerations mostly limit investigations to single hormone administrations. To circumvent this issue we assessed the influence of continuous high-dose hormone application in adult female-to-male transsexuals. Subjects underwent magnetic resonance imaging before and after 4 weeks of testosterone treatment, with each scan including structural, diffusion weighted and functional imaging. Voxel-based morphometry analysis showed decreased gray matter volume with increasing levels of bioavailable testosterone exclusively in Broca's and Wernicke's areas. Particularly, this may link known sex differences in language performance to the influence of testosterone on relevant brain regions. Using probabilistic tractography, we further observed that longitudinal changes in testosterone negatively predicted changes in mean diffusivity of the corresponding structural connection passing through the extreme capsule. Considering a related increase in myelin staining in rodents, this potentially reflects a strengthening of the fiber tract particularly involved in language comprehension. Finally, functional images at resting-state were evaluated, showing increased functional connectivity between the two brain regions with increasing testosterone levels. These findings suggest testosterone-dependent neuroplastic adaptations in adulthood within language-specific brain regions and connections. Importantly, deteriorations in gray matter volume seem to be compensated by enhancement of corresponding structural and functional connectivity. Hum Brain Mapp 37:1738-1748, 2016. © 2016 Wiley Periodicals, Inc. © 2016 The Authors Human Brain Mapping Published by Wiley Periodicals, Inc.

  12. Mapping human brain lesions and their functional consequences.

    Science.gov (United States)

    Karnath, Hans-Otto; Sperber, Christoph; Rorden, Christopher

    2018-01-15

    Neuroscience has a long history of inferring brain function by examining the relationship between brain injury and subsequent behavioral impairments. The primary advantage of this method over correlative methods is that it can tell us if a certain brain region is necessary for a given cognitive function. In addition, lesion-based analyses provide unique insights into clinical deficits. In the last decade, statistical voxel-based lesion behavior mapping (VLBM) emerged as a powerful method for understanding the architecture of the human brain. This review illustrates how VLBM improves our knowledge of functional brain architecture, as well as how it is inherently limited by its mass-univariate approach. A wide array of recently developed methods appear to supplement traditional VLBM. This paper provides an overview of these new methods, including the use of specialized imaging modalities, the combination of structural imaging with normative connectome data, as well as multivariate analyses of structural imaging data. We see these new methods as complementing rather than replacing traditional VLBM, providing synergistic tools to answer related questions. Finally, we discuss the potential for these methods to become established in cognitive neuroscience and in clinical applications. Copyright © 2017 Elsevier Inc. All rights reserved.

  13. Human Brain Stem Structures Respond Differentially to Noxious Heat

    Directory of Open Access Journals (Sweden)

    Alexander eRitter

    2013-09-01

    Full Text Available Concerning the physiological correlates of pain, the brain stem is considered to be one core region that is activated by noxious input. In animal studies, different slopes of skin heating (SSH with noxious heat led to activation in different columns of the midbrain periaqueductal grey (PAG. The present study aimed at finding a method for differentiating structures in PAG and other brain stem structures, which are associated with different qualities of pain in humans according to the structures that were associated with different behavioral significances to noxious thermal stimulation in animals. Brain activity was studied by fMRI in healthy subjects in response to steep and shallow SSH with noxious heat. We found differential activation to different SSH in the PAG and the rostral ventromedial medulla (RVM. In a second experiment we demonstrate that the different SSH were associated with different pain qualities. Our experiments provide evidence that brainstem structures, i.e. the PAG and the RVM, become differentially activated by different SSH. Therefore, different SSH can be utilized when brain stem structures are investigated and when it is aimed to activate these structures differentially. Moreover, percepts of first pain were elicited by shallow SSH whereas percepts of second pain were elicited by steep SSH. The stronger activation of these brain stem structures to SSH, eliciting percepts of second vs. first pain, might be of relevance for activating different coping strategies in response to the noxious input with the two types of SSH.

  14. Relationship of Topology, Multiscale Phase Synchronization, and State Transitions in Human Brain Networks

    Directory of Open Access Journals (Sweden)

    Minkyung Kim

    2017-06-01

    Full Text Available How the brain reconstitutes consciousness and cognition after a major perturbation like general anesthesia is an important question with significant neuroscientific and clinical implications. Recent empirical studies in animals and humans suggest that the recovery of consciousness after anesthesia is not random but ordered. Emergence patterns have been classified as progressive and abrupt transitions from anesthesia to consciousness, with associated differences in duration and electroencephalogram (EEG properties. We hypothesized that the progressive and abrupt emergence patterns from the unconscious state are associated with, respectively, continuous and discontinuous synchronization transitions in functional brain networks. The discontinuous transition is explainable with the concept of explosive synchronization, which has been studied almost exclusively in network science. We used the Kuramato model, a simple oscillatory network model, to simulate progressive and abrupt transitions in anatomical human brain networks acquired from diffusion tensor imaging (DTI of 82 brain regions. To facilitate explosive synchronization, distinct frequencies for hub nodes with a large frequency disassortativity (i.e., higher frequency nodes linking with lower frequency nodes, or vice versa were applied to the brain network. In this simulation study, we demonstrated that both progressive and abrupt transitions follow distinct synchronization processes at the individual node, cluster, and global network levels. The characteristic synchronization patterns of brain regions that are “progressive and earlier” or “abrupt but delayed” account for previously reported behavioral responses of gradual and abrupt emergence from the unconscious state. The characteristic network synchronization processes observed at different scales provide new insights into how regional brain functions are reconstituted during progressive and abrupt emergence from the unconscious

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

    Science.gov (United States)

    Guillozet-Bongaarts, Angela L.; Shen, Elaine H.; Ng, Lydia; Miller, Jeremy A.; van de Lagemaat, Louie N.; Smith, Kimberly A.; Ebbert, Amanda; Riley, Zackery L.; Abajian, Chris; Beckmann, Christian F.; Bernard, Amy; Bertagnolli, Darren; Boe, Andrew F.; Cartagena, Preston M.; Chakravarty, M. Mallar; Chapin, Mike; Chong, Jimmy; Dalley, Rachel A.; David Daly, Barry; Dang, Chinh; Datta, Suvro; Dee, Nick; Dolbeare, Tim A.; Faber, Vance; Feng, David; Fowler, David R.; Goldy, Jeff; Gregor, Benjamin W.; Haradon, Zeb; Haynor, David R.; Hohmann, John G.; Horvath, Steve; Howard, Robert E.; Jeromin, Andreas; Jochim, Jayson M.; Kinnunen, Marty; Lau, Christopher; Lazarz, Evan T.; Lee, Changkyu; Lemon, Tracy A.; Li, Ling; Li, Yang; Morris, John A.; Overly, Caroline C.; Parker, Patrick D.; Parry, Sheana E.; Reding, Melissa; Royall, Joshua J.; Schulkin, Jay; Sequeira, Pedro Adolfo; Slaughterbeck, Clifford R.; Smith, Simon C.; Sodt, Andy J.; Sunkin, Susan M.; Swanson, Beryl E.; Vawter, Marquis P.; Williams, Derric; Wohnoutka, Paul; Zielke, H. Ronald; Geschwind, Daniel H.; Hof, Patrick R.; Smith, Stephen M.; Koch, Christof; Grant, Seth G. N.; Jones, Allan R.

    2014-01-01

    Neuroanatomically precise, genome-wide maps of transcript distributions are critical resources to complement genomic sequence data and to correlate functional and genetic brain architecture. Here we describe the generation and analysis of a transcriptional atlas of the adult human brain, comprising extensive histological analysis and comprehensive microarray profiling of ~900 neuroanatomically precise subdivisions in two individuals. Transcriptional regulation varies enormously by anatomical location, with different regions and their constituent cell types displaying robust molecular signatures that are highly conserved between individuals. Analysis of differential gene expression and gene co-expression relationships demonstrates that brain-wide variation strongly reflects the distributions of major cell classes such as neurons, oligodendrocytes, astrocytes and microglia. Local neighbourhood relationships between fine anatomical subdivisions are associated with discrete neuronal subtypes and genes involved with synaptic transmission. The neocortex displays a relatively homogeneous transcriptional pattern, but with distinct features associated selectively with primary sensorimotor cortices and with enriched frontal lobe expression. Notably, the spatial topography of the neocortex is strongly reflected in its molecular topography— the closer two cortical regions, the more similar their transcriptomes. This freely accessible online data resource forms a high-resolution transcriptional baseline for neurogenetic studies of normal and abnormal human brain function. PMID:22996553

  16. Morphometric human embryonic brain features according to developmental stage.

    Science.gov (United States)

    Kobayashi, Ami; Ishizu, Koichi; Yamada, Shigehito; Uwabe, Chigako; Kose, Katsumi; Takakuwa, Tetsuya

    2016-04-01

    The present study investigated linear, area, and volume measurements of human brain samples according to Carnegie stages (CS) in an attempt to select suitable morphometric features that reflect embryonic development. Using magnetic resonance imaging, we measured seven linear segments, three separate areas, and three regional volumes in 101 samples between CS13 and 23. Brain volume was determined via manual segmentation of the magnetic resonance image, whereby a formula was generated to estimate the volume of each linear measurement. All parameters correlated with crown-rump length. Bitemporal length and mesencephalic height increased linearly according to the CS, and a high correlation between bitemporal length and both whole-brain (r = 0.98) and prosencephalon (r = 0.99) volumes was found when brain cavity volume was excluded. Morphometric data related to human embryonic stages are valuable for correcting and comparing sonographic data. The present approach may contribute to improvements in prenatal diagnostics by enabling the selection of more suitable measurements during early embryonic stages. © 2016 John Wiley & Sons, Ltd. © 2016 John Wiley & Sons, Ltd.

  17. The Speculative Neuroscience of the Future Human Brain

    Directory of Open Access Journals (Sweden)

    Robert A. Dielenberg

    2013-05-01

    Full Text Available The hallmark of our species is our ability to hybridize symbolic thinking with behavioral output. We began with the symmetrical hand axe around 1.7 mya and have progressed, slowly at first, then with greater rapidity, to producing increasingly more complex hybridized products. We now live in the age where our drive to hybridize has pushed us to the brink of a neuroscientific revolution, where for the first time we are in a position to willfully alter the brain and hence, our behavior and evolution. Nootropics, transcranial direct current stimulation (tDCS, transcranial magnetic stimulation (TMS, deep brain stimulation (DBS and invasive brain mind interface (BMI technology are allowing humans to treat previously inaccessible diseases as well as open up potential vistas for cognitive enhancement. In the future, the possibility exists for humans to hybridize with BMIs and mobile architectures. The notion of self is becoming increasingly extended. All of this to say: are we in control of our brains, or are they in control of us?

  18. Drug delivery to the human brain via the cerebrospinal fluid

    International Nuclear Information System (INIS)

    Howden, L.; Aroussi, A.; Vloeberghs, M.

    2003-01-01

    This Study investigates the flow of Cerebrospinal Fluid (CSF) inside the human ventricular system with particular emphasis on drug path flow for the purpose of medical drug injections. The investigation is conducted using the computational fluid dynamics package FLUENT. The role of the ventricular system is very important in protecting the brain from injury by cushioning it against the cranium during sudden movements. If for any reason the passage of CSF through the ventricular system is blocked (usually by stenosis) then a condition known as Hydrocephalus occurs, where by the blocked CSF causes the Intra Cranial Pressure (ICP) inside the brain to rise. If this is not treated then severe brain damage and death can occur. Previous work conducted by the authors on this subject has focused on the technique of ventriculostomy to treat hydrocephalus. The present study carries on from the previous work but focuses on delivering medical drugs to treat brain tumors that are conventionally not accessible and which require complicated surgical procedures to remove them. The study focuses on the possible paths for delivering drugs to tumors in the human nervous system through conventionally accessible locations without major surgery. The results of the investigation have shown that it is possible to reach over 95% of the ventricular system by injection of drugs however the results also show that there are many factors that can affect the drug flow paths through the ventricular system and thus the areas reachable, by these drugs. (author)

  19. Drug delivery to the human brain via the cerebrospinal fluid

    Energy Technology Data Exchange (ETDEWEB)

    Howden, L.; Aroussi, A. [Univ. of Nottingham, School of Mechanical, Material, Manufacturing Engineering and Managements, Nottingham (United Kingdom)]. E-mail: eaxljh@nottingham.ac.uk; Vloeberghs, M. [Queens Medical Centre, Dept. of Child Health, Nottingham (United Kingdom)

    2003-07-01

    This Study investigates the flow of Cerebrospinal Fluid (CSF) inside the human ventricular system with particular emphasis on drug path flow for the purpose of medical drug injections. The investigation is conducted using the computational fluid dynamics package FLUENT. The role of the ventricular system is very important in protecting the brain from injury by cushioning it against the cranium during sudden movements. If for any reason the passage of CSF through the ventricular system is blocked (usually by stenosis) then a condition known as Hydrocephalus occurs, where by the blocked CSF causes the Intra Cranial Pressure (ICP) inside the brain to rise. If this is not treated then severe brain damage and death can occur. Previous work conducted by the authors on this subject has focused on the technique of ventriculostomy to treat hydrocephalus. The present study carries on from the previous work but focuses on delivering medical drugs to treat brain tumors that are conventionally not accessible and which require complicated surgical procedures to remove them. The study focuses on the possible paths for delivering drugs to tumors in the human nervous system through conventionally accessible locations without major surgery. The results of the investigation have shown that it is possible to reach over 95% of the ventricular system by injection of drugs however the results also show that there are many factors that can affect the drug flow paths through the ventricular system and thus the areas reachable, by these drugs. (author)

  20. Can fruits and vegetables be used as substitute phantoms for normal human brain tissues in magnetic resonance imaging?

    International Nuclear Information System (INIS)

    Teramoto, Daisuke; Ushioda, Yuichi; Sasaki, Ayaka; Sakurai Yuki; Nagahama, Hiroshi; Nakamura, Manami; Sugimori, Hiroyuki; Sakata, Motomichi

    2013-01-01

    Various custom-made phantoms designed to optimize magnetic resonance imaging (MRI) sequences have been created and subsequently reported in Japanese Society of Radiological Technology (JSRT). However, custom-made phantoms that correctly match the T 1 -value and T 2 -values of human brain tissue (gray matter and white matter) cannot be made easily or quickly. The aim of this project was to search for alternative materials, such as fruits and vegetables, for optimizing MRI sequences. The following eight fruits and vegetables were investigated: apple, tomato, melon, apple mango (Mangifera indica), banana, avocado, peach, and eggplant. Their potential was studied for use in modeling phantoms of normal human brain tissues. MRI (T 1 - and T 2 -weighted sequences) was performed on the human brain and the fruits and vegetables using various concentrations of contrast medium (gadolinium) in the same size tubes as the custom-made phantom. The authors compared the signal intensity (SI) in human brain tissue (gray matter and white matter) with that of the fruits and the custom-made phantom. The T 1 and T 2 values were measured for banana tissue and compared with those for human brain tissue in the literature. Our results indicated that banana tissue is similar to human brain tissue (both gray matter and white matter). Banana tissue can thus be employed as an alternative phantom for the human brain for the purpose of MRI. (author)

  1. Differential regional brain growth and rotation of the prenatal human tentorium cerebelli.

    Science.gov (United States)

    Jeffery, Nathan

    2002-02-01

    Folds of dura mater, the falx cerebri and tentorium cerebelli, traverse the vertebrate endocranial cavity and compartmentalize the brain. Previous studies suggest that the tentorial fold has adopted an increasingly important role in supporting the increased load of the cerebrum during human evolution, brought about by encephalization and an adaptation to bipedal posture. Ontogenetic studies of the fetal tentorium suggest that its midline profile rotates inferoposteriorly towards the foramen magnum in response to disproportionate growth of the cerebrum. This study tests the hypothesis that differential growth of the cerebral and cerebellar components of the brain underlies the inferoposterior rotation of the tentorium cerebelli during human fetal development. Brain volumes and tentorial angles were taken from high-resolution magnetic resonance images of 46 human fetuses ranging from 10 to 29 gestational weeks. Apart from the expected increases of both supratentorial and infratentorial brain volumes with age, the results confirm previous studies showing a significant relative enlargement of the supratentorial volume. Correlated with this enlargement was a rotation of the midline section of the tentorium towards the posterior cranial base. These findings support the concept that increases of supratentorial volume relative to infratentorial volume affect an inferoposterior rotation of the human fetal tentorium cerebelli. These results are discussed in the context of the role played by the tentorium cerebelli during human evolution and underline implications for phylogenetic and ontogenetic models of encephalization.

  2. Cluster imaging of multi-brain networks (CIMBN: a general framework for hyperscanning and modeling a group of interacting brains

    Directory of Open Access Journals (Sweden)

    Lian eDuan

    2015-07-01

    Full Text Available Studying the neural basis of human social interactions is a key topic in the field of social neuroscience. Brain imaging studies in this field usually focus on the neural correlates of the social interactions between two participants. However, as the participant number further increases, even by a small amount, great difficulties raise. One challenge is how to concurrently scan all the interacting brains with high ecological validity, especially for a large number of participants. The other challenge is how to effectively model the complex group interaction behaviors emerging from the intricate neural information exchange among a group of socially organized people. Confronting these challenges, we propose a new approach called Cluster Imaging of Multi-brain Networks (CIMBN. CIMBN consists of two parts. The first part is a cluster imaging technique with high ecological validity based on multiple functional near-infrared spectroscopy (fNIRS systems. Using this technique, we can easily extend the simultaneous imaging capacity of social neuroscience studies up to dozens of participants. The second part of CIMBN is a multi-brain network (MBN modeling method based on graph theory. By taking each brain as a network node and the relationship between any two brains as a network edge, one can construct a network model for a group of interacting brains. The emergent group social behaviors can then be studied using the network’s properties, such as its topological structure and information exchange efficiency. Although there is still much work to do, as a general framework for hyperscanning and modeling a group of interacting brains, CIMBN can provide new insights into the neural correlates of group social interactions, and advance social neuroscience and social psychology.

  3. A Novel Human Body Area Network for Brain Diseases Analysis.

    Science.gov (United States)

    Lin, Kai; Xu, Tianlang

    2016-10-01

    Development of wireless sensor and mobile communication technology provide an unprecedented opportunity for realizing smart and interactive healthcare systems. Designing such systems aims to remotely monitor the health and diagnose the diseases for users. In this paper, we design a novel human body area network for brain diseases analysis, which is named BABDA. Considering the brain is one of the most complex organs in the human body, the BABDA system provides four function modules to ensure the high quality of the analysis result, which includes initial data collection, data correction, data transmission and comprehensive data analysis. The performance evaluation conducted in a realistic environment with several criteria shows the availability and practicability of the BABDA system.

  4. Right-lateralized brain oscillations in human spatial navigation.

    Science.gov (United States)

    Jacobs, Joshua; Korolev, Igor O; Caplan, Jeremy B; Ekstrom, Arne D; Litt, Brian; Baltuch, Gordon; Fried, Itzhak; Schulze-Bonhage, Andreas; Madsen, Joseph R; Kahana, Michael J

    2010-05-01

    During spatial navigation, lesion and functional imaging studies suggest that the right hemisphere has a unique functional role. However, studies of direct human brain recordings have not reported interhemisphere differences in navigation-related oscillatory activity. We investigated this apparent discrepancy using intracranial electroencephalographic recordings from 24 neurosurgical patients playing a virtual taxi driver game. When patients were virtually moving in the game, brain oscillations at various frequencies increased in amplitude compared with periods of virtual stillness. Using log-linear analysis, we analyzed the region and frequency specificities of this pattern and found that neocortical movement-related gamma oscillations (34-54 Hz) were significantly lateralized to the right hemisphere, especially in posterior neocortex. We also observed a similar right lateralization of gamma oscillations related to searching for objects at unknown virtual locations. Thus, our results indicate that gamma oscillations in the right neocortex play a special role in human spatial navigation.

  5. Learning sculpts the spontaneous activity of the resting human brain

    OpenAIRE

    Lewis, Christopher M.; Baldassarre, Antonello; Committeri, Giorgia; Romani, Gian Luca; Corbetta, Maurizio

    2009-01-01

    The brain is not a passive sensory-motor analyzer driven by environmental stimuli, but actively maintains ongoing representations that may be involved in the coding of expected sensory stimuli, prospective motor responses, and prior experience. Spontaneous cortical activity has been proposed to play an important part in maintaining these ongoing, internal representations, although its functional role is not well understood. One spontaneous signal being intensely investigated in the human brai...

  6. Segmenting Brain Tissues from Chinese Visible Human Dataset by Deep-Learned Features with Stacked Autoencoder

    Directory of Open Access Journals (Sweden)

    Guangjun Zhao

    2016-01-01

    Full Text Available Cryosection brain images in Chinese Visible Human (CVH dataset contain rich anatomical structure information of tissues because of its high resolution (e.g., 0.167 mm per pixel. Fast and accurate segmentation of these images into white matter, gray matter, and cerebrospinal fluid plays a critical role in analyzing and measuring the anatomical structures of human brain. However, most existing automated segmentation methods are designed for computed tomography or magnetic resonance imaging data, and they may not be applicable for cryosection images due to the imaging difference. In this paper, we propose a supervised learning-based CVH brain tissues segmentation method that uses stacked autoencoder (SAE to automatically learn the deep feature representations. Specifically, our model includes two successive parts where two three-layer SAEs take image patches as input to learn the complex anatomical feature representation, and then these features are sent to Softmax classifier for inferring the labels. Experimental results validated the effectiveness of our method and showed that it outperformed four other classical brain tissue detection strategies. Furthermore, we reconstructed three-dimensional surfaces of these tissues, which show their potential in exploring the high-resolution anatomical structures of human brain.

  7. Investigation of G72 (DAOA expression in the human brain

    Directory of Open Access Journals (Sweden)

    Hirsch Steven

    2008-12-01

    Full Text Available Abstract Background Polymorphisms at the G72/G30 locus on chromosome 13q have been associated with schizophrenia or bipolar disorder in more than ten independent studies. Even though the genetic findings are very robust, the physiological role of the predicted G72 protein has thus far not been resolved. Initial reports suggested G72 as an activator of D-amino acid oxidase (DAO, supporting the glutamate dysfunction hypothesis of schizophrenia. However, these findings have subsequently not been reproduced and reports of endogenous human G72 mRNA and protein expression are extremely limited. In order to better understand the function of this putative schizophrenia susceptibility gene, we attempted to demonstrate G72 mRNA and protein expression in relevant human brain regions. Methods The expression of G72 mRNA was studied by northern blotting and semi-quantitative SYBR-Green and Taqman RT-PCR. Protein expression in human tissue lysates was investigated by western blotting using two custom-made specific anti-G72 peptide antibodies. An in-depth in silico analysis of the G72/G30 locus was performed in order to try and identify motifs or regulatory elements that provide insight to G72 mRNA expression and transcript stability. Results Despite using highly sensitive techniques, we failed to identify significant levels of G72 mRNA in a variety of human tissues (e.g. adult brain, amygdala, caudate nucleus, fetal brain, spinal cord and testis human cell lines or schizophrenia/control post mortem BA10 samples. Furthermore, using western blotting in combination with sensitive detection methods, we were also unable to detect G72 protein in a number of human brain regions (including cerebellum and amygdala, spinal cord or testis. A detailed in silico analysis provides several lines of evidence that support the apparent low or absent expression of G72. Conclusion Our results suggest that native G72 protein is not normally present in the tissues that we analysed

  8. Modeling brain resonance phenomena using a neural mass model.

    Directory of Open Access Journals (Sweden)

    Andreas Spiegler

    2011-12-01

    Full Text Available Stimulation with rhythmic light flicker (photic driving plays an important role in the diagnosis of schizophrenia, mood disorder, migraine, and epilepsy. In particular, the adjustment of spontaneous brain rhythms to the stimulus frequency (entrainment is used to assess the functional flexibility of the brain. We aim to gain deeper understanding of the mechanisms underlying this technique and to predict the effects of stimulus frequency and intensity. For this purpose, a modified Jansen and Rit neural mass model (NMM of a cortical circuit is used. This mean field model has been designed to strike a balance between mathematical simplicity and biological plausibility. We reproduced the entrainment phenomenon observed in EEG during a photic driving experiment. More generally, we demonstrate that such a single area model can already yield very complex dynamics, including chaos, for biologically plausible parameter ranges. We chart the entire parameter space by means of characteristic Lyapunov spectra and Kaplan-Yorke dimension as well as time series and power spectra. Rhythmic and chaotic brain states were found virtually next to each other, such that small parameter changes can give rise to switching from one to another. Strikingly, this characteristic pattern of unpredictability generated by the model was matched to the experimental data with reasonable accuracy. These findings confirm that the NMM is a useful model of brain dynamics during photic driving. In this context, it can be used to study the mechanisms of, for example, perception and epileptic seizure generation. In particular, it enabled us to make predictions regarding the stimulus amplitude in further experiments for improving the entrainment effect.

  9. Bayesian Joint Modeling of Multiple Brain Functional Networks

    OpenAIRE

    Lukemire, Joshua; Kundu, Suprateek; Pagnoni, Giuseppe; Guo, Ying

    2017-01-01

    Brain function is organized in coordinated modes of spatio-temporal activity (functional networks) exhibiting an intrinsic baseline structure with variations under different experimental conditions. Existing approaches for uncovering such network structures typically do not explicitly model shared and differential patterns across networks, thus potentially reducing the detection power. We develop an integrative modeling approach for jointly modeling multiple brain networks across experimental...

  10. Temperament, character and serotonin activity in the human brain

    DEFF Research Database (Denmark)

    Tuominen, L; Salo, J; Hirvonen, J

    2013-01-01

    The psychobiological model of personality by Cloninger and colleagues originally hypothesized that interindividual variability in the temperament dimension 'harm avoidance' (HA) is explained by differences in the activity of the brain serotonin system. We assessed brain serotonin transporter (5-HTT......-existing Temperament and Character Inventory (TCI) scores. A total of 22 subjects free of psychiatric and somatic disorders were included in the matched high- and low-HA groups. The main outcome measure was regional 5-HTT binding potential (BPND) in high- and low-HA groups estimated with PET and [11C]N,N-dimethyl-2...

  11. Mapping the human brain during a specific Vojta's tactile input: the ipsilateral putamen's role.

    Science.gov (United States)

    Sanz-Esteban, Ismael; Calvo-Lobo, Cesar; Ríos-Lago, Marcos; Álvarez-Linera, Juan; Muñoz-García, Daniel; Rodríguez-Sanz, David

    2018-03-01

    A century of research in human brain parcellation has demonstrated that different brain areas are associated with functional tasks. New neuroscientist perspectives to achieve the parcellation of the human brain have been developed to know the brain areas activation and its relationship with different stimuli. This descriptive study aimed to compare brain regions activation by specific tactile input (STI) stimuli according to the Vojta protocol (STI-group) to a non-STI stimulation (non-STI-group). An exploratory functional magnetic resonance imaging (fMRI) study was performed. The 2 groups of participants were passively stimulated by an expert physical therapist using the same paradigm structure, although differing in the place of stimulation. The stimulation was presented to participants using a block design in all cases. A sample of 16 healthy participants, 5 men and 11 women, with mean age 31.31 ± 8.13 years was recruited. Indeed, 12 participants were allocated in the STI-group and 4 participants in the non-STI-group. fMRI was used to map the human brain in vivo while these tactile stimuli were being applied. Data were analyzed using a general linear model in SPM12 implemented in MATLAB. Differences between groups showed a greater activation in the right cortical areas (temporal and frontal lobes), subcortical regions (thalamus, brainstem, and basal nuclei), and in the cerebellum (anterior lobe). STI-group had specific difference brain activation areas, such as the ipsilateral putamen. Future studies should study clinical implications in neurorehabilitation patients.

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

    OpenAIRE

    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 hemisphe...

  13. A new microcontroller-based human brain hypothermia system.

    Science.gov (United States)

    Kapidere, Metin; Ahiska, Raşit; Güler, Inan

    2005-10-01

    Many studies show that artificial hypothermia of brain in conditions of anesthesia with the rectal temperature lowered down to 33 degrees C produces pronounced prophylactic effect protecting the brain from anoxia. Out of the methods employed now in clinical practice for reducing the oxygen consumption by the cerebral tissue, the most efficacious is craniocerebral hypothermia (CCH). It is finding even more extensive application in cardiovascular surgery, neurosurgery, neurorenimatology and many other fields of medical practice. In this study, a microcontroller-based designed human brain hypothermia system (HBHS) is designed and constructed. The system is intended for cooling and heating the brain. HBHS consists of a thermoelectric hypothermic helmet, a control and a power unit. Helmet temperature is controlled by 8-bit PIC16F877 microcontroller which is programmed using MPLAB editor. Temperature is converted to 10-bit digital and is controlled automatically by the preset values which have been already entered in the microcontroller. Calibration is controlled and the working range is tested. Temperature of helmet is controlled between -5 and +46 degrees C by microcontroller, with the accuracy of +/-0.5 degrees C.

  14. Permeability of PEGylated immunoarsonoliposomes through in vitro blood brain barrier-medulloblastoma co-culture models for brain tumor therapy.

    Science.gov (United States)

    Al-Shehri, Abdulghani; Favretto, Marco E; Ioannou, Panayiotis V; Romero, Ignacio A; Couraud, Pierre-Olivier; Weksler, Babette Barbash; Parker, Terry L; Kallinteri, Paraskevi

    2015-03-01

    Owing to restricted access of pharmacological agents into the brain due to blood brain barrier (BBB) there is a need: 1. to develop a more representative 3-D-co-culture model of tumor-BBB interaction to investigate drug and nanoparticle transport into the brain for diagnostic and therapeutic evaluation. 2. to address the lack of new alternative methods to animal testing according to replacement-reduction-refinement principles. In this work, in vitro BBB-medulloblastoma 3-D-co-culture models were established using immortalized human primary brain endothelial cells (hCMEC/D3). hCMEC/D3 cells were cultured in presence and in absence of two human medulloblastoma cell lines on Transwell membranes. In vitro models were characterized for BBB formation, zonula occludens-1 expression and permeability to dextran. Transferrin receptors (Tfr) expressed on hCMEC/D3 were exploited to facilitate arsonoliposome (ARL) permeability through the BBB to the tumor by covalently attaching an antibody specific to human Tfr. The effect of anticancer ARLs on hCMEC/D3 was assessed. In vitro BBB and BBB-tumor co-culture models were established successfully. BBB permeability was affected by the presence of tumor aggregates as suggested by increased permeability of ARLs. There was a 6-fold and 8-fold increase in anti-Tfr-ARL uptake into VC312R and BBB-DAOY co-culture models, respectively, compared to plain ARLs. The three-dimensional models might be appropriate models to study the transport of various drugs and nanocarriers (liposomes and immunoarsonoliposomes) through the healthy and diseased BBB. The immunoarsonoliposomes can be potentially used as anticancer agents due to good tolerance of the in vitro BBB model to their toxic effect.

  15. Insulin and C-peptide in human brain neurons (insulin/C-peptide/brain peptides/immunohistochemistry/radioimmunoassay)

    International Nuclear Information System (INIS)

    Dorn, A.; Bernstein, H.G.; Rinne, A.; Hahn, H.J.; Ziegler, M.

    1983-01-01

    The regional distribution and cellular localization of insulin and C-peptide immunoreactivities were studied in human cadaver brains using the indirect immunofluorescence method, the peroxidase-antiperoxidase technique, and radioimmunoassay. Products of the immune reactions to both polypeptides were observed in most nerve cells in all areas of the brain examined. Immunostaining was mainly restricted to the cell soma and proximal dendrites. Radioimmunoassay revealed that human brain contains insulin and C-peptide in concentrations much higher than the blood, the highest being in the hypothalamus. These findings support the hypothesis that the 'brain insulin' is - at least in part - produced in the CNS. (author)

  16. Ubiquity and specificity of reinforcement signals throughout the human brain.

    Science.gov (United States)

    Vickery, Timothy J; Chun, Marvin M; Lee, Daeyeol

    2011-10-06

    Reinforcements and punishments facilitate adaptive behavior in diverse domains ranging from perception to social interactions. A conventional approach to understanding the corresponding neural substrates focuses on the basal ganglia and its dopaminergic projections. Here, we show that reinforcement and punishment signals are surprisingly ubiquitous in the gray matter of nearly every subdivision of the human brain. Humans played either matching-pennies or rock-paper-scissors games against computerized opponents while being scanned using fMRI. Multivoxel pattern analysis was used to decode previous choices and their outcomes, and to predict upcoming choices. Whereas choices were decodable from a confined set of brain structures, their outcomes were decodable from nearly all cortical and subcortical structures. In addition, signals related to both reinforcements and punishments were recovered reliably in many areas and displayed patterns not consistent with salience-based explanations. Thus, reinforcement and punishment might play global modulatory roles in the entire brain. Copyright © 2011 Elsevier Inc. All rights reserved.

  17. Brain repair after stroke--a novel neurological model.

    Science.gov (United States)

    Small, Steven L; Buccino, Giovanni; Solodkin, Ana

    2013-12-01

    Following stroke, patients are commonly left with debilitating motor and speech impairments. This article reviews the state of the art in neurological repair for stroke and proposes a new model for the future. We suggest that stroke treatment--from the time of the ictus itself to living with the consequences--must be fundamentally neurological, from limiting the extent of injury at the outset, to repairing the consequent damage. Our model links brain and behaviour by targeting brain circuits, and we illustrate the model though action observation treatment, which aims to enhance brain network connectivity. The model is based on the assumptions that the mechanisms of neural repair inherently involve cellular and circuit plasticity, that brain plasticity is a synaptic phenomenon that is largely stimulus-dependent, and that brain repair required both physical and behavioural interventions that are tailored to reorganize specific brain circuits. We review current approaches to brain repair after stroke and present our new model, and discuss the biological foundations, rationales, and data to support our novel approach to upper-extremity and language rehabilitation. We believe that by enhancing plasticity at the level of brain network interactions, this neurological model for brain repair could ultimately lead to a cure for stroke.

  18. Brain repair after stroke—a novel neurological model

    Science.gov (United States)

    Small, Steven L.; Buccino, Giovanni; Solodkin, Ana

    2017-01-01

    Following stroke, patients are commonly left with debilitating motor and speech impairments. This article reviews the state of the art in neurological repair for stroke and proposes a new model for the future. We suggest that stroke treatment—from the time of the ictus itself to living with the consequences—must be fundamentally neurological, from limiting the extent of injury at the outset, to repairing the consequent damage. Our model links brain and behaviour by targeting brain circuits, and we illustrate the model though action observation treatment, which aims to enhance brain network connectivity. The model is based on the assumptions that the mechanisms of neural repair inherently involve cellular and circuit plasticity, that brain plasticity is a synaptic phenomenon that is largely stimulus-dependent, and that brain repair required both physical and behavioural interventions that are tailored to reorganize specific brain circuits. We review current approaches to brain repair after stroke and present our new model, and discuss the biological foundations, rationales, and data to support our novel approach to upper-extremity and language rehabilitation. We believe that by enhancing plasticity at the level of brain network interactions, this neurological model for brain repair could ultimately lead to a cure for stroke. PMID:24217509

  19. "Brain drain, brain gain. . . Brain sustain?" : Challenges in building Portuguese human research capacity

    NARCIS (Netherlands)

    Hasanefendic, Sandra

    2017-01-01

    This paper presents a systematic but essentially descriptive account of the policy measure of stimulating human research capacity development under the policy program "Commitment to Science" in Portugal in the period 2006-2009. It explores the conditions that contributed to the development of the

  20. Mathematical models of human retina.

    Science.gov (United States)

    Tălu, Stefan

    2011-01-01

    To describe the human retina, due the absence of complete topographical data, mathematical models are required. The mathematical formula permits a relatively simple representation to explore the physical and optical characteristics of the retina, with particular parameters. Advanced mathematical models are applied for human vision studies, solid modelling and biomechanical behavior of the retina. The accurate modelling of the retina is important in the development of visual prostheses. The objective of this paper is to present an overview of researches for human retina modelling using mathematical models.

  1. [Isolation and identification of brain tumor stem cells from human brain neuroepithelial tumors].

    Science.gov (United States)

    Fang, Jia-sheng; Deng, Yong-wen; Li, Ming-chu; Chen, Feng-Hua; Wang, Yan-jin; Lu, Ming; Fang, Fang; Wu, Jun; Yang, Zhuan-yi; Zhou, Xang-yang; Wang, Fei; Chen, Cheng

    2007-01-30

    To establish a simplified culture system for the isolation of brain tumor stem cells (BTSCs) from the tumors of human neuroepithelial tissue, to observe the growth and differentiation pattern of BTSCs, and to investigate their expression of the specific markers. Twenty-six patients with brain neuroepithelial tumors underwent tumor resection. Two pieces of tumor tissues were taken from each tumor to be dissociated, triturated into single cells in sterile DMEM-F12 medium, and then filtered. The tumor cells were seeded at a concentration of 200,000 viable cells per mL into serum-free DMEM-F12 medium simply supplemented with B27, human basic fibroblast growth factor (20 microg/L), human epidermal growth factor (20 microg /L), insulin (4 U/L), L-glutamine, penicillin and streptomycin. After the primary brain tumor spheres (BTSs) were generated, they were triturated again and passed in fresh medium. Limiting dilution assay was performed to observe the monoclone formation. 5-bromodeoxyuridine (BrdU) incorporation test was performed to observe the proliferation of the BTS. The BTSCs were cultured in mitogen-free DMEM-F12 medium supplemented with 10% fetal bovine serum to observe their differentiation. Immunocytochemistry was used to examine the expression of CD133 and nestin, specific markers of BTSC, and the rate of CD133 positive cells. Only a minority of subsets of cells from the tumors of neuroepithelial tissue had the capacity to survive, proliferate, and generate free-floating neurosphere-like BTSs in the simplified serum-free medium. These cells attached to the poly-L-lysine coated coverslips in the serum-supplemented medium and differentiated. The BTSCs were CD133 and nestin positive. The rate of CD133 positive cells in the tumor specimens was (21 +/- 6.2)% - (38 +/- 7.0)%. A new simplified culture system for the isolation of BTSCs is established. The tumors of human neuroepithelial tissue contain CD133 and nestin positive tumor stem cells which can be isolated

  2. On a Mathematical Model of Brain Activities

    International Nuclear Information System (INIS)

    Fichtner, K.-H.; Fichtner, L.; Freudenberg, W.; Ohya, M.

    2007-01-01

    The procedure of recognition can be described as follows: There is a set of complex signals stored in the memory. Choosing one of these signals may be interpreted as generating a hypothesis concerning an 'expexted view of the world'. Then the brain compares a signal arising from our senses with the signal chosen from the memory leading to a change of the state of both signals. Furthermore, measurements of that procedure like EEG or MEG are based on the fact that recognition of signals causes a certain loss of excited neurons, i.e. the neurons change their state from 'excited' to 'nonexcited'. For that reason a statistical model of the recognition process should reflect both--the change of the signals and the loss of excited neurons. A first attempt to explain the process of recognition in terms of quantum statistics was given. In the present note it is not possible to present this approach in detail. In lieu we will sketch roughly a few of the basic ideas and structures of the proposed model of the recognition process (Section). Further, we introduce the basic spaces and justify the choice of spaces used in this approach. A more elaborate presentation including all proofs will be given in a series of some forthcoming papers. In this series also the procedures of creation of signals from the memory, amplification, accumulation and transformation of input signals, and measurements like EEG and MEG will be treated in detail

  3. Can structure predict function in the human brain?

    Science.gov (United States)

    Honey, Christopher J; Thivierge, Jean-Philippe; Sporns, Olaf

    2010-09-01

    Over the past decade, scientific interest in the properties of large-scale spontaneous neural dynamics has intensified. Concurrently, novel technologies have been developed for characterizing the connective anatomy of intra-regional circuits and inter-regional fiber pathways. It will soon be possible to build computational models that incorporate these newly detailed structural network measurements to make predictions of neural dynamics at multiple scales. Here, we review the practicality and the value of these efforts, while at the same time considering in which cases and to what extent structure does determine neural function. Studies of the healthy brain, of neural development, and of pathology all yield examples of direct correspondences between structural linkage and dynamical correlation. Theoretical arguments further support the notion that brain network topology and spatial embedding should strongly influence network dynamics. Although future models will need to be tested more quantitatively and against a wider range of empirical neurodynamic features, our present large-scale models can already predict the macroscopic pattern of dynamic correlation across the brain. We conclude that as neuroscience grapples with datasets of increasing completeness and complexity, and attempts to relate the structural and functional architectures discovered at different neural scales, the value of computational modeling will continue to grow. Copyright (c) 2010 Elsevier Inc. All rights reserved.

  4. Assessing human brain impedance using simultaneous surface and intracerebral recordings.

    Science.gov (United States)

    Ranta, Radu; Le Cam, Steven; Tyvaert, Louise; Louis-Dorr, Valérie

    2017-02-20

    Most of the literature on the brain impedance proposes a frequency-independent resistive model. Recently, this conclusion was tackled by a series of papers (Bédard et al., 2006; Bédard and Destexhe, 2009; Gomes et al., 2016), based on microscopic sale modeling and measurements. Our paper aims to investigate the impedance issue using simultaneous in vivo depth and surface signals recorded during intracerebral electrical stimulation of epileptic patients, involving a priori different tissues with different impedances. Our results confirm the conclusions from Logothethis et al. (2007): there is no evidence of frequency dependence of the brain tissue impedance (more precisely, there is no difference, in terms of frequency filtering, between the brain and the skull bone), at least at a macroscopic scale. In order to conciliate findings from both microscopic and macroscopic scales, we recall different neural/synaptic current generators' models from the literature and we propose an original computational model, based on fractional dynamics. Copyright © 2016 IBRO. Published by Elsevier Ltd. All rights reserved.

  5. Toward the holistic, reference, and extendable atlas of the human brain, head, and neck.

    Science.gov (United States)

    Nowinski, Wieslaw L

    2015-06-01

    Despite numerous efforts, a fairly complete (holistic) anatomical model of the whole, normal, adult human brain, which is required as the reference in brain studies and clinical applications, has not yet been constructed. Our ultimate objective is to build this kind of atlas from advanced in vivo imaging. This work presents the taxonomy of our currently developed brain atlases and addresses the design, content, functionality, and current results in the holistic atlas development as well as atlas usefulness and future directions. We have developed to date 35 commercial brain atlases (along with numerous research prototypes), licensed to 63 companies and institutions, and made available to medical societies, organizations, medical schools, and individuals. These atlases have been applied in education, research, and clinical applications. Hundreds of thousands of patients have been treated by using our atlases. Based on this experience, the first version of the holistic and reference atlas of the brain, head, and neck has been developed and made available. The atlas has been created from multispectral 3 and 7 Tesla and high-resolution CT in vivo scans. It is fully 3D, scalable, interactive, and highly detailed with about 3,000 labeled components. This atlas forms a foundation for the development of a multi-level molecular, cellular, anatomical, physiological, and behavioral brain atlas platform.

  6. Social Rewards and Social Networks in the Human Brain.

    Science.gov (United States)

    Fareri, Dominic S; Delgado, Mauricio R

    2014-08-01

    The rapid development of social media and social networking sites in human society within the past decade has brought about an increased focus on the value of social relationships and being connected with others. Research suggests that we pursue socially valued or rewarding outcomes-approval, acceptance, reciprocity-as a means toward learning about others and fulfilling social needs of forming meaningful relationships. Focusing largely on recent advances in the human neuroimaging literature, we review findings highlighting the neural circuitry and processes that underlie pursuit of valued rewarding outcomes across non-social and social domains. We additionally discuss emerging human neuroimaging evidence supporting the idea that social rewards provide a gateway to establishing relationships and forming social networks. Characterizing the link between social network, brain, and behavior can potentially identify contributing factors to maladaptive influences on decision making within social situations. © The Author(s) 2014.

  7. Individual brain structure and modelling predict seizure propagation.

    Science.gov (United States)

    Proix, Timothée; Bartolomei, Fabrice; Guye, Maxime; Jirsa, Viktor K

    2017-03-01

    See Lytton (doi:10.1093/awx018) for a scientific commentary on this article.Neural network oscillations are a fundamental mechanism for cognition, perception and consciousness. Consequently, perturbations of network activity play an important role in the pathophysiology of brain disorders. When structural information from non-invasive brain imaging is merged with mathematical modelling, then generative brain network models constitute personalized in silico platforms for the exploration of causal mechanisms of brain function and clinical hypothesis testing. We here demonstrate with the example of drug-resistant epilepsy that patient-specific virtual brain models derived from diffusion magnetic resonance imaging have sufficient predictive power to improve diagnosis and surgery outcome. In partial epilepsy, seizures originate in a local network, the so-called epileptogenic zone, before recruiting other close or distant brain regions. We create personalized large-scale brain networks for 15 patients and simulate the individual seizure propagation patterns. Model validation is performed against the presurgical stereotactic electroencephalography data and the standard-of-care clinical evaluation. We demonstrate that the individual brain models account for the patient seizure propagation patterns, explain the variability in postsurgical success, but do not reliably augment with the use of patient-specific connectivity. Our results show that connectome-based brain network models have the capacity to explain changes in the organization of brain activity as observed in some brain disorders, thus opening up avenues towards discovery of novel clinical interventions. © The Author (2017). Published by Oxford University Press on behalf of the Guarantors of Brain.

  8. Infection and upregulation of proinflammatory cytokines in human brain vascular pericytes by human cytomegalovirus

    Directory of Open Access Journals (Sweden)

    Alcendor Donald J

    2012-05-01

    Full Text Available Abstract Background Congenital human cytomegalovirus (HCMV infections can result in CNS abnormalities in newborn babies including vision loss, mental retardation, motor deficits, seizures, and hearing loss. Brain pericytes play an essential role in the development and function of the blood–brain barrier yet their unique role in HCMV dissemination and neuropathlogy has not been reported. Methods Primary human brain vascular pericytes were exposed to a primary clinical isolate of HCMV designated ‘SBCMV’. Infectivity was analyzed by microscopy, immunofluorescence, Western blot, and qRT-PCR. Microarrays were performed to identify proinflammatory cytokines upregulated after SBCMV exposure, and the results validated by real-time quantitative polymerase chain reaction (qPCR methodology. In situ cytokine expression of pericytes after exposure to HCMV was examined by ELISA and in vivo evidence of HCMV infection of brain pericytes was shown by dual-labeled immunohistochemistry. Results HCMV-infected human brain vascular pericytes as evidenced by several markers. Using a clinical isolate of HCMV (SBCMV, microscopy of infected pericytes showed virion production and typical cytomegalic cytopathology. This finding was confirmed by the expression of major immediate early and late virion proteins and by the presence of HCMV mRNA. Brain pericytes were fully permissive for CMV lytic replication after 72 to 96 hours in culture compared to human astrocytes or human brain microvascular endothelial cells (BMVEC. However, temporal transcriptional expression of pp65 virion protein after SBCMV infection was lower than that seen with the HCMV Towne laboratory strain. Using RT-PCR and dual-labeled immunofluorescence, proinflammatory cytokines CXCL8/IL-8, CXCL11/ITAC, and CCL5/Rantes were upregulated in SBCMV-infected cells, as were tumor necrosis factor-alpha (TNF-alpha, interleukin-1 beta (IL-1beta, and interleukin-6 (IL-6. Pericytes exposed to SBCMV elicited

  9. Infection and upregulation of proinflammatory cytokines in human brain vascular pericytes by human cytomegalovirus

    Science.gov (United States)

    2012-01-01

    Background Congenital human cytomegalovirus (HCMV) infections can result in CNS abnormalities in newborn babies including vision loss, mental retardation, motor deficits, seizures, and hearing loss. Brain pericytes play an essential role in the development and function of the blood–brain barrier yet their unique role in HCMV dissemination and neuropathlogy has not been reported. Methods Primary human brain vascular pericytes were exposed to a primary clinical isolate of HCMV designated ‘SBCMV’. Infectivity was analyzed by microscopy, immunofluorescence, Western blot, and qRT-PCR. Microarrays were performed to identify proinflammatory cytokines upregulated after SBCMV exposure, and the results validated by real-time quantitative polymerase chain reaction (qPCR) methodology. In situ cytokine expression of pericytes after exposure to HCMV was examined by ELISA and in vivo evidence of HCMV infection of brain pericytes was shown by dual-labeled immunohistochemistry. Results HCMV-infected human brain vascular pericytes as evidenced by several markers. Using a clinical isolate of HCMV (SBCMV), microscopy of infected pericytes showed virion production and typical cytomegalic cytopathology. This finding was confirmed by the expression of major immediate early and late virion proteins and by the presence of HCMV mRNA. Brain pericytes were fully permissive for CMV lytic replication after 72 to 96 hours in culture compared to human astrocytes or human brain microvascular endothelial cells (BMVEC). However, temporal transcriptional expression of pp65 virion protein after SBCMV infection was lower than that seen with the HCMV Towne laboratory strain. Using RT-PCR and dual-labeled immunofluorescence, proinflammatory cytokines CXCL8/IL-8, CXCL11/ITAC, and CCL5/Rantes were upregulated in SBCMV-infected cells, as were tumor necrosis factor-alpha (TNF-alpha), interleukin-1 beta (IL-1beta), and interleukin-6 (IL-6). Pericytes exposed to SBCMV elicited higher levels of IL-6

  10. Olfactory Dysfunctions and Decreased Nitric Oxide Production in the Brain of Human P301L Tau Transgenic Mice.

    Science.gov (United States)

    Hu, Yang; Ding, Wenting; Zhu, Xiaonan; Chen, Ruzhu; Wang, Xuelan

    2016-04-01

    Different patterns of olfactory dysfunction have been found in both patients and mouse models of Alzheimer's Disease. However, the underlying mechanism of the dysfunction remained unknown. Deficits of nitric oxide production in brain can cause olfactory dysfunction by preventing the formation of olfactory memory. The aim of this study was to investigate the behavioral changes in olfaction and alterations in metabolites of nitric oxide, nitrate/nitrite concentration, in the brain of human P301L tau transgenic mice. The tau mice showed impairments in olfaction and increased abnormal phosphorylation of Tau protein at AT8 in different brain areas, especially in olfactory bulb. We now report that these olfactory deficits and Tau pathological changes were accompanied by decreased nitrate/nitrite concentration in the brain, especially in the olfactory bulb, and reduced expression of nNOS in the brain of tau mice. These findings provided evidence of olfactory dysfunctions correlated with decreased nitric oxide production in the brain of tau mice.

  11. The retention of [99mTc]-d,l-HM-PAO in the human brain after intracarotid bolus injection

    DEFF Research Database (Denmark)

    Lassen, N A; Andersen, A R; Friberg, L

    1988-01-01

    , the lipophilic tracer inside the brain, and the hydrophilic form retained in the brain. The retention curve initially drops abruptly, corresponding to the nonextracted fraction of the injectate leaving the brain; it then falls exponentially towards the asymptotic level of the fractional steady-state retention R......[99mTc]-d,l-HM-PAO (HM-PAO) was injected rapidly into the internal carotid artery and its retention in the brain was recorded by external scintillation cameras in eight human subjects. A model is described based on three compartments: the lipophilic tracer in the blood pool of the brain....... Cerebral blood flow (F) was measured using the xenon-133 intracarotid injection method. The first-pass extraction E of HM-PAO was calculated from F using an empiric regression equation. The residue curves for the whole brain after intracarotid HM-PAO injection were analyzed to yield a retention fraction (R...

  12. Modeling human color categorization

    NARCIS (Netherlands)

    van den Broek, Egon; Schouten, Th.E.; Kisters, P.M.F.

    A unique color space segmentation method is introduced. It is founded on features of human cognition, where 11 color categories are used in processing color. In two experiments, human subjects were asked to categorize color stimuli into these 11 color categories, which resulted in markers for a

  13. Bayesian exponential random graph modeling of whole-brain structural networks across lifespan

    OpenAIRE

    Sinke, Michel R T; Dijkhuizen, Rick M; Caimo, Alberto; Stam, Cornelis J; Otte, Wim

    2016-01-01

    Descriptive neural network analyses have provided important insights into the organization of structural and functional networks in the human brain. However, these analyses have limitations for inter-subject or between-group comparisons in which network sizes and edge densities may differ, such as in studies on neurodevelopment or brain diseases. Furthermore, descriptive neural network analyses lack an appropriate generic null model and a unifying framework. These issues may be solved with an...

  14. Why our brains cherish humanity: Mirror neurons and colamus humanitatem

    Directory of Open Access Journals (Sweden)

    John R. Skoyles

    2008-06-01

    Full Text Available Commonsense says we are isolated. After all, our bodies are physically separate. But Seneca’s colamus humanitatem, and John Donne’s observation that “no man is an island” suggests we are neither entirely isolated nor separate. A recent discovery in neuroscience—that of mirror neurons—argues that the brain and the mind is neither built nor functions remote from what happens in other individuals. What are mirror neurons? They are brain cells that process both what happens to or is done by an individual, and, as it were, its perceived “refl ection,” when that same thing happens or is done by another individual. Thus, mirror neurons are both activated when an individual does a particular action, and when that individual perceives that same action done by another. The discovery of mirror neurons suggests we need to radically revise our notions of human nature since they offer a means by which we may not be so separated as we think. Humans unlike other apes are adapted to mirror interact nonverbally when together. Notably, our faces have been evolved to display agile and nimble movements. While this is usually explained as enabling nonverbal communication, a better description would be nonverbal commune based upon mirror neurons. I argue we cherish humanity, colamus humanitatem, because mirror neurons and our adapted mirror interpersonal interface blur the physical boundaries that separate us.

  15. Mapping Multiplex Hubs in Human Functional Brain Networks.

    Science.gov (United States)

    De Domenico, Manlio; Sasai, Shuntaro; Arenas, Alex

    2016-01-01

    Typical brain networks consist of many peripheral regions and a few highly central ones, i.e., hubs, playing key functional roles in cerebral inter-regional interactions. Studies have shown that networks, obtained from the analysis of specific frequency components of brain activity, present peculiar architectures with unique profiles of region centrality. However, the identification of hubs in networks built from different frequency bands simultaneously is still a challenging problem, remaining largely unexplored. Here we identify each frequency component with one layer of a multiplex network and face this challenge by exploiting the recent advances in the analysis of multiplex topologies. First, we show that each frequency band carries unique topological information, fundamental to accurately model brain functional networks. We then demonstrate that hubs in the multiplex network, in general different from those ones obtained after discarding or aggregating the measured signals as usual, provide a more accurate map of brain's most important functional regions, allowing to distinguish between healthy and schizophrenic populations better than conventional network approaches.

  16. Stochastic Models of Human Errors

    Science.gov (United States)

    Elshamy, Maged; Elliott, Dawn M. (Technical Monitor)

    2002-01-01

    Humans play an important role in the overall reliability of engineering systems. More often accidents and systems failure are traced to human errors. Therefore, in order to have meaningful system risk analysis, the reliability of the human element must be taken into consideration. Describing the human error process by mathematical models is a key to analyzing contributing factors. Therefore, the objective of this research effort is to establish stochastic models substantiated by sound theoretic foundation to address the occurrence of human errors in the processing of the space shuttle.

  17. Imaging neuroreceptors in the human brain in health and disease

    International Nuclear Information System (INIS)

    Wagner, H.N. Jr.; Dannals, R.F.; Frost, J.J.

    1985-01-01

    For nearly a century it has been known that chemical activity accompanies mental activity, but only recently has it been possible to begin to examine its exact nature. Positron-emitting radioactive tracers have made it possible to study the chemistry of the human brain in health and disease, using chiefly cyclotron-produced radionuclides, carbon-11, fluorine-18 and oxygen-15. It is now well established that measurable increases in regional cerebral blood flow, and glucose and oxygen metabolism accompany the mental functions of perception, cognition, emotion and motion. On 25 May 1983 the first imaging of a neuroreceptor in the human brain was accomplished with carbon-11 N-methyl spiperone, a ligand that binds preferentially to dopamine-2 receptors, 80% of which are located in the caudate nucleus and putamen. Quantitative imaging of serotonin-2, opiate, benzodiazapine and muscarinic cholinergic receptors has subsequently been accomplished. In studies of normal men and women, it has been found that dopamine and serotonin receptor activity decreases dramatically with age, such a decrease being more pronounced in men than in women and greater in the case of dopamine-2 receptors than in serotonin-2 receptors. Preliminary studies of patients with neuropsychiatric disorders suggest that dopamine-2 receptor activity is diminished in the caudate nucleus of patients with Huntington's disease. Positron tomography permits a quantitative assay of picomolar quantities of neuroreceptors within the living human brain. Studies of patients with Parkinson's disease, Alzheimer's disease, depression, anxiety, schizophrenia, acute and chronic pain states and drug addiction are now in progress. (author)

  18. A Novel Magnetic Resonance Imaging (MRI) Approach for Measuring Weak Electric Currents Inside the Human Brain

    DEFF Research Database (Denmark)

    Göksu, Cihan

    ) and magnetoencephalography (MEG) source localization, or localization of pathological tissues. For example, the accuracy of electric field simulations for NIBS techniques is currently reduced by assigning inaccurate ohmic conductivity values taken from literature to different brain tissues. Therefore, the knowledge......Knowing the electrical conductivity and current density distribution inside the human brain will be useful in various biomedical applications, i.e. for improving the efficiency of non-invasive brain stimulation (NIBS) techniques, the accuracy of electroencephalography (EEG...... of individual ohmic conductivity values may open up the possibility of creating more realistic and accurate head models, which may ameliorate the simulations and practical use of NIBS techniques. Magnetic resonance current density imaging (MRCDI) and magnetic resonance electrical impedance tomography (MREIT...

  19. Accelerated evolution of the ASPM gene controlling brain size begins prior to human brain expansion.

    Directory of Open Access Journals (Sweden)

    Natalay Kouprina

    2004-05-01

    Full Text Available Primary microcephaly (MCPH is a neurodevelopmental disorder characterized by global reduction in cerebral cortical volume. The microcephalic brain has a volume comparable to that of early hominids, raising the possibility that some MCPH genes may have been evolutionary targets in the expansion of the cerebral cortex in mammals and especially primates. Mutations in ASPM, which encodes the human homologue of a fly protein essential for spindle function, are the most common known cause of MCPH. Here we have isolated large genomic clones containing the complete ASPM gene, including promoter regions and introns, from chimpanzee, gorilla, orangutan, and rhesus macaque by transformation-associated recombination cloning in yeast. We have sequenced these clones and show that whereas much of the sequence of ASPM is substantially conserved among primates, specific segments are subject to high Ka/Ks ratios (nonsynonymous/synonymous DNA changes consistent with strong positive selection for evolutionary change. The ASPM gene sequence shows accelerated evolution in the African hominoid clade, and this precedes hominid brain expansion by several million years. Gorilla and human lineages show particularly accelerated evolution in the IQ domain of ASPM. Moreover, ASPM regions under positive selection in primates are also the most highly diverged regions between primates and nonprimate mammals. We report the first direct application of TAR cloning technology to the study of human evolution. Our data suggest that evolutionary selection of specific segments of the ASPM sequence strongly relates to differences in cerebral cortical size.

  20. The neurophysiology of language: Insights from non-invasive brain stimulation in the healthy human brain.

    Science.gov (United States)

    Hartwigsen, Gesa

    2015-09-01

    With the advent of non-invasive brain stimulation (NIBS), a new decade in the study of language has started. NIBS allows for testing the functional relevance of language-related brain activation and enables the researcher to investigate how neural activation changes in response to focal perturbations. This review focuses on the application of NIBS in the healthy brain. First, some basic mechanisms will be introduced and the prerequisites for carrying out NIBS studies of language are addressed. The next section outlines how NIBS can be used to characterize the contribution of the stimulated area to a task. In this context, novel approaches such as multifocal transcranial magnetic stimulation and the condition-and-perturb approach are discussed. The third part addresses the combination of NIBS and neuroimaging in the study of plasticity. These approaches are particularly suited to investigate short-term reorganization in the healthy brain and may inform models of language recovery in post-stroke aphasia. Copyright © 2014 The Author. Published by Elsevier Inc. All rights reserved.

  1. Human blood-brain barrier insulin-like growth factor receptor

    International Nuclear Information System (INIS)

    Duffy, K.R.; Pardridge, W.M.; Rosenfeld, R.G.

    1988-01-01

    Insulin-like growth factor (IGF)-1 and IGF-2, may be important regulatory molecules in the CNS. Possible origins of IGFs in brain include either de novo synthesis or transport of circulating IGFs from blood into brain via receptor mediated transcytosis mechanisms at the brain capillary endothelial wall, ie, the blood-brain barrier (BBB). In the present studies, isolated human brain capillaries are used as an in vitro model system of the human BBB and the characteristics of IGF-1 or IGF-2 binding to this preparation were assessed. The total binding of IGF-2 at 37 degrees C exceeded 130% per mg protein and was threefold greater than the total binding for IGF-1. However, at 37 degrees C nonsaturable binding equaled total binding, suggesting that endocytosis is rate limiting at physiologic temperatures. Binding studies performed at 4 degrees C slowed endocytosis to a greater extent than membrane binding, and specific binding of either IGF-1 or IGF-2 was detectable. Scatchard plots for either peptide were linear and the molar dissociation constant of IGF-1 and IGF-2 binding was 2.1 +/- 0.4 and 1.1 +/- 0.1 nmol/L, respectively. Superphysiologic concentrations of porcine insulin inhibited the binding of both IGF-1 (ED50 = 2 micrograms/mL) and IGF-2 (ED50 = 0.5 microgram/mL). Affinity cross linking of 125 I-IGF-1, 125 I-IGF-2, and 125 I-insulin to isolated human brain capillaries was performed using disuccinimidylsuberate (DSS). These studies revealed a 141 kd binding site for both IGF-1 and IGF-2, and a 133 kd binding site for insulin

  2. Interleukin-6 release from the human brain during prolonged exercise

    DEFF Research Database (Denmark)

    Nybo, Lars; Nielsen, Bodil; Pedersen, Bente Klarlund

    2002-01-01

    bouts: one bout with a normal (38 degrees C) and the other with an elevated (39.5 degrees C) core temperature. The cerebral IL-6 response was determined on the basis of internal jugular venous to arterial IL-6 differences and global cerebral blood flow. There was no net release or uptake of IL-6...... influence of hyperthermia. In conclusion, IL-6 is released from the brain during prolonged exercise in humans and it appears that the duration of the exercise rather than the increase in body temperature dictates the cerebral IL-6 response....

  3. Transcriptome analysis of human brain tissue identifies reduced expression of complement complex C1Q Genes in Rett syndrome.

    Science.gov (United States)

    Lin, Peijie; Nicholls, Laura; Assareh, Hassan; Fang, Zhiming; Amos, Timothy G; Edwards, Richard J; Assareh, Amelia A; Voineagu, Irina

    2016-06-06

    MECP2, the gene mutated in the majority of Rett syndrome cases, is a transcriptional regulator that can activate or repress transcription. Although the transcription regulatory function of MECP2 has been known for over a decade, it remains unclear how transcriptional dysregulation leads to the neurodevelopmental disorder. Notably, little convergence was previously observed between the genes abnormally expressed in the brain of Rett syndrome mouse models and those identified in human studies. Here we carried out a comprehensive transcriptome analysis of human brain tissue from Rett syndrome brain using both RNA-seq and microarrays. We identified over two hundred differentially expressed genes, and identified the complement C1Q complex genes (C1QA, C1QB and C1QC) as a point of convergence between gene expression changes in human and mouse Rett syndrome brain. The results of our study support a role for alterations in the expression level of C1Q complex genes in RTT pathogenesis.

  4. Unmasking Language Lateralization in Human Brain Intrinsic Activity

    Science.gov (United States)

    McAvoy, Mark; Mitra, Anish; Coalson, Rebecca S.; d'Avossa, Giovanni; Keidel, James L.; Petersen, Steven E.; Raichle, Marcus E.

    2016-01-01

    Lateralization of function is a fundamental feature of the human brain as exemplified by the left hemisphere dominance of language. Despite the prominence of lateralization in the lesion, split-brain and task-based fMRI literature, surprisingly little asymmetry has been revealed in the increasingly popular functional imaging studies of spontaneous fluctuations in the fMRI BOLD signal (so-called resting-state fMRI). Here, we show the global signal, an often discarded component of the BOLD signal in resting-state studies, reveals a leftward asymmetry that maps onto regions preferential for semantic processing in left frontal and temporal cortex and the right cerebellum and a rightward asymmetry that maps onto putative attention-related regions in right frontal, temporoparietal, and parietal cortex. Hemispheric asymmetries in the global signal resulted from amplitude modulation of the spontaneous fluctuations. To confirm these findings obtained from normal, healthy, right-handed subjects in the resting-state, we had them perform 2 semantic processing tasks: synonym and numerical magnitude judgment and sentence comprehension. In addition to establishing a new technique for studying lateralization through functional imaging of the resting-state, our findings shed new light on the physiology of the global brain signal. PMID:25636911

  5. MR-visible brain water content in human acute stroke

    DEFF Research Database (Denmark)

    Gideon, P; Rosenbaum, S; Sperling, B

    1999-01-01

    Quantification of metabolite concentrations by proton magnetic resonance spectroscopy (1H-MRS) in the human brain using water as an internal standard is based on the assumption that water content does not change significantly in pathologic brain tissue. To test this, we used 1H-MRS to estimate...... brain water content during the course of cerebral infarction. Measurements were performed serially in the acute, subacute, and chronic phase of infarction. Fourteen patients with acute cerebral infarction were examined as well as 9 healthy controls. To correlate with regional cerebral blood flow (r......CBF) SPECT-scanning using 99mTc-HMPAO as flow tracer was performed in the patients. Mean water content (SD) in the infarct area was 37.7 (5.1); 41.8 (4.8); 35.2 (5.4); and 39.3 (5.1) mol x [kg wet weight](-1) at 0-3; 4-7; 8-21; and >180 days after stroke, respectively. Water content increased between Day 0...

  6. The structure of creative cognition in the human brain

    Science.gov (United States)

    Jung, Rex E.; Mead, Brittany S.; Carrasco, Jessica; Flores, Ranee A.

    2013-01-01

    Creativity is a vast construct, seemingly intractable to scientific inquiry—perhaps due to the vague concepts applied to the field of research. One attempt to limit the purview of creative cognition formulates the construct in terms of evolutionary constraints, namely that of blind variation and selective retention (BVSR). Behaviorally, one can limit the “blind variation” component to idea generation tests as manifested by measures of divergent thinking. The “selective retention” component can be represented by measures of convergent thinking, as represented by measures of remote associates. We summarize results from measures of creative cognition, correlated with structural neuroimaging measures including structural magnetic resonance imaging (sMRI), diffusion tensor imaging (DTI), and proton magnetic resonance spectroscopy (1H-MRS). We also review lesion studies, considered to be the “gold standard” of brain-behavioral studies. What emerges is a picture consistent with theories of disinhibitory brain features subserving creative cognition, as described previously (Martindale, 1981). We provide a perspective, involving aspects of the default mode network (DMN), which might provide a “first approximation” regarding how creative cognition might map on to the human brain. PMID:23847503

  7. Integrated Environmental Modelling: Human decisions, human challenges

    Science.gov (United States)

    Glynn, Pierre D.

    2015-01-01

    Integrated Environmental Modelling (IEM) is an invaluable tool for understanding the complex, dynamic ecosystems that house our natural resources and control our environments. Human behaviour affects the ways in which the science of IEM is assembled and used for meaningful societal applications. In particular, human biases and heuristics reflect adaptation and experiential learning to issues with frequent, sharply distinguished, feedbacks. Unfortunately, human behaviour is not adapted to the more diffusely experienced problems that IEM typically seeks to address. Twelve biases are identified that affect IEM (and science in general). These biases are supported by personal observations and by the findings of behavioural scientists. A process for critical analysis is proposed that addresses some human challenges of IEM and solicits explicit description of (1) represented processes and information, (2) unrepresented processes and information, and (3) accounting for, and cognizance of, potential human biases. Several other suggestions are also made that generally complement maintaining attitudes of watchful humility, open-mindedness, honesty and transparent accountability. These suggestions include (1) creating a new area of study in the behavioural biogeosciences, (2) using structured processes for engaging the modelling and stakeholder communities in IEM, and (3) using ‘red teams’ to increase resilience of IEM constructs and use.

  8. Integrated Environmental Modelling: human decisions, human challenges

    Science.gov (United States)

    Glynn, Pierre D.

    2015-01-01

    Integrated Environmental Modelling (IEM) is an invaluable tool for understanding the complex, dynamic ecosystems that house our natural resources and control our environments. Human behaviour affects the ways in which the science of IEM is assembled and used for meaningful societal applications. In particular, human biases and heuristics reflect adaptation and experiential learning to issues with frequent, sharply distinguished, feedbacks. Unfortunately, human behaviour is not adapted to the more diffusely experienced problems that IEM typically seeks to address. Twelve biases are identified that affect IEM (and science in general). These biases are supported by personal observations and by the findings of behavioural scientists. A process for critical analysis is proposed that addresses some human challenges of IEM and solicits explicit description of (1) represented processes and information, (2) unrepresented processes and information, and (3) accounting for, and cognizance of, potential human biases. Several other suggestions are also made that generally complement maintaining attitudes of watchful humility, open-mindedness, honesty and transparent accountability. These suggestions include (1) creating a new area of study in the behavioural biogeosciences, (2) using structured processes for engaging the modelling and stakeholder communities in IEM, and (3) using ‘red teams’ to increase resilience of IEM constructs and use.

  9. Stable functional networks exhibit consistent timing in the human brain.

    Science.gov (United States)

    Chapeton, Julio I; Inati, Sara K; Zaghloul, Kareem A

    2017-03-01

    Despite many advances in the study of large-scale human functional networks, the question of timing, stability, and direction of communication between cortical regions has not been fully addressed. At the cellular level, neuronal communication occurs through axons and dendrites, and the time required for such communication is well defined and preserved. At larger spatial scales, however, the relationship between timing, direction, and communication between brain regions is less clear. Here, we use a measure of effective connectivity to identify connections between brain regions that exhibit communication with consistent timing. We hypothesized that if two brain regions are communicating, then knowledge of the activity in one region should allow an external observer to better predict activity in the other region, and that such communication involves a consistent time delay. We examine this question using intracranial electroencephalography captured from nine human participants with medically refractory epilepsy. We use a coupling measure based on time-lagged mutual information to identify effective connections between brain regions that exhibit a statistically significant increase in average mutual information at a consistent time delay. These identified connections result in sparse, directed functional networks that are stable over minutes, hours, and days. Notably, the time delays associated with these connections are also highly preserved over multiple time scales. We characterize the anatomic locations of these connections, and find that the propagation of activity exhibits a preferred posterior to anterior temporal lobe direction, consistent across participants. Moreover, networks constructed from connections that reliably exhibit consistent timing between anatomic regions demonstrate features of a small-world architecture, with many reliable connections between anatomically neighbouring regions and few long range connections. Together, our results demonstrate

  10. The brain's silent messenger: using selective attention to decode human thought for brain-based communication.

    Science.gov (United States)

    Naci, Lorina; Cusack, Rhodri; Jia, Vivian Z; Owen, Adrian M

    2013-05-29

    The interpretation of human thought from brain activity, without recourse to speech or action, is one of the most provoking and challenging frontiers of modern neuroscience. In particular, patients who are fully conscious and awake, yet, due to brain damage, are unable to show any behavioral responsivity, expose the limits of the neuromuscular system and the necessity for alternate forms of communication. Although it is well established that selective attention can significantly enhance the neural representation of attended sounds, it remains, thus far, untested as a response modality for brain-based communication. We asked whether its effect could be reliably used to decode answers to binary (yes/no) questions. Fifteen healthy volunteers answered questions (e.g., "Do you have brothers or sisters?") in the fMRI scanner, by selectively attending to the appropriate word ("yes" or "no"). Ninety percent of the answers were decoded correctly based on activity changes within the attention network. The majority of volunteers conveyed their answers with less than 3 min of scanning, suggesting that this technique is suited for communication in a reasonable amount of time. Formal comparison with the current best-established fMRI technique for binary communication revealed improved individual success rates and scanning times required to detect responses. This novel fMRI technique is intuitive, easy to use in untrained participants, and reliably robust within brief scanning times. Possible applications include communication with behaviorally nonresponsive patients.

  11. Exceptional evolutionary divergence of human muscle and brain metabolomes parallels human cognitive and physical uniqueness

    DEFF Research Database (Denmark)

    Bozek, Katarzyna; Wei, Yuning; Yan, Zheng

    2014-01-01

    Metabolite concentrations reflect the physiological states of tissues and cells. However, the role of metabolic changes in species evolution is currently unknown. Here, we present a study of metabolome evolution conducted in three brain regions and two non-neural tissues from humans, chimpanzees...

  12. Telomere length modulation in human astroglial brain tumors.

    Directory of Open Access Journals (Sweden)

    Domenico La Torre

    Full Text Available BACKGROUND: Telomeres alteration during carcinogenesis and tumor progression has been described in several cancer types. Telomeres length is stabilized by telomerase (h-TERT and controlled by several proteins that protect telomere integrity, such as the Telomere Repeat-binding Factor (TRF 1 and 2 and the tankyrase-poli-ADP-ribose polymerase (TANKs-PARP complex. OBJECTIVE: To investigate telomere dysfunction in astroglial brain tumors we analyzed telomeres length, telomerase activity and the expression of a panel of genes controlling the length and structure of telomeres in tissue samples obtained in vivo from astroglial brain tumors with different grade of malignancy. MATERIALS AND METHODS: Eight Low Grade Astrocytomas (LGA, 11 Anaplastic Astrocytomas (AA and 11 Glioblastoma Multiforme (GBM samples were analyzed. Three samples of normal brain tissue (NBT were used as controls. Telomeres length was assessed through Southern Blotting. Telomerase activity was evaluated by a telomere repeat amplification protocol (TRAP assay. The expression levels of TRF1, TRF2, h-TERT and TANKs-PARP complex were determined through Immunoblotting and RT-PCR. RESULTS: LGA were featured by an up-regulation of TRF1 and 2 and by shorter telomeres. Conversely, AA and GBM were featured by a down-regulation of TRF1 and 2 and an up-regulation of both telomerase and TANKs-PARP complex. CONCLUSIONS: In human astroglial brain tumours, up-regulation of TRF1 and TRF2 occurs in the early stages of carcinogenesis determining telomeres shortening and genomic instability. In a later stage, up-regulation of PARP-TANKs and telomerase activation may occur together with an ADP-ribosylation of TRF1, causing a reduced ability to bind telomeric DNA, telomeres elongation and tumor malignant progression.

  13. Animal models of brain dysfunction in phenylketonuria

    NARCIS (Netherlands)

    Martynyuk, A. E.; van Spronsen, F. J.; Van der Zee, E. A.

    2010-01-01

    Phenylketonuria (PKU) is a metabolic disorder that results in significant brain dysfunction if untreated. Although phenylalanine restricted diets instituted at birth have clearly improved PKU outcomes, neuropsychological deficits and neurological changes still represent substantial problems. The

  14. Statistical Challenges in Modeling Big Brain Signals

    KAUST Repository

    Yu, Zhaoxia

    2017-11-01

    Brain signal data are inherently big: massive in amount, complex in structure, and high in dimensions. These characteristics impose great challenges for statistical inference and learning. Here we review several key challenges, discuss possible solutions, and highlight future research directions.

  15. Selectively altering belief formation in the human brain

    Science.gov (United States)

    Sharot, Tali; Kanai, Ryota; Marston, David; Korn, Christoph W.; Rees, Geraint; Dolan, Raymond J.

    2012-01-01

    Humans form beliefs asymmetrically; we tend to discount bad news but embrace good news. This reduced impact of unfavorable information on belief updating may have important societal implications, including the generation of financial market bubbles, ill preparedness in the face of natural disasters, and overly aggressive medical decisions. Here, we selectively improved people’s tendency to incorporate bad news into their beliefs by disrupting the function of the left (but not right) inferior frontal gyrus using transcranial magnetic stimulation, thereby eliminating the engrained “good news/bad news effect.” Our results provide an instance of how selective disruption of regional human brain function paradoxically enhances the ability to incorporate unfavorable information into beliefs of vulnerability. PMID:23011798

  16. Selectively altering belief formation in the human brain.

    Science.gov (United States)

    Sharot, Tali; Kanai, Ryota; Marston, David; Korn, Christoph W; Rees, Geraint; Dolan, Raymond J

    2012-10-16

    Humans form beliefs asymmetrically; we tend to discount bad news but embrace good news. This reduced impact of unfavorable information on belief updating may have important societal implications, including the generation of financial market bubbles, ill preparedness in the face of natural disasters, and overly aggressive medical decisions. Here, we selectively improved people's tendency to incorporate bad news into their beliefs by disrupting the function of the left (but not right) inferior frontal gyrus using transcranial magnetic stimulation, thereby eliminating the engrained "good news/bad news effect." Our results provide an instance of how selective disruption of regional human brain function paradoxically enhances the ability to incorporate unfavorable information into beliefs of vulnerability.

  17. Language representation in the human brain: evidence from cortical mapping.

    Science.gov (United States)

    Bhatnagar, S C; Mandybur, G T; Buckingham, H W; Andy, O J

    2000-09-01

    The manner in which the human brain processes grammatical-syntactic and lexical-semantic functions has been extensively debated in neurolinguistics. The discreteness and selectivity of the representation of syntactic-morphological properties in the dominant frontal cortex and the representation of the lexical-semantics in the temporo-parietal cortex have been questioned. Three right-handed adult male neurosurgical patients undergoing left craniotomy for intractable seizures were evaluated using various grammatical and semantic tasks during cortical mapping. The sampling of language tasks consisted of trials with stimulation (experimental) and without stimulation (control) from sites in the dominant fronto-temporo-parietal cortex The sampling of language implicated a larger cortical area devoted to language (syntactic-morphological and lexical-semantic) tasks. Further, a large part of the fronto-parieto-temporal cortex was involved with syntactic-morphological functions. However, only the parieto-temporal sites were implicated with the ordering of lexicon in sentence construction. These observations suggest that the representation of language in the human brain may be columnar or multilayered. Copyright 2000 Academic Press.

  18. Mapping human brain networks with cortico-cortical evoked potentials

    Science.gov (United States)

    Keller, Corey J.; Honey, Christopher J.; Mégevand, Pierre; Entz, Laszlo; Ulbert, Istvan; Mehta, Ashesh D.

    2014-01-01

    The cerebral cortex forms a sheet of neurons organized into a network of interconnected modules that is highly expanded in humans and presumably enables our most refined sensory and cognitive abilities. The links of this network form a fundamental aspect of its organization, and a great deal of research is focusing on understanding how information flows within and between different regions. However, an often-overlooked element of this connectivity regards a causal, hierarchical structure of regions, whereby certain nodes of the cortical network may exert greater influence over the others. While this is difficult to ascertain non-invasively, patients undergoing invasive electrode monitoring for epilepsy provide a unique window into this aspect of cortical organization. In this review, we highlight the potential for cortico-cortical evoked potential (CCEP) mapping to directly measure neuronal propagation across large-scale brain networks with spatio-temporal resolution that is superior to traditional neuroimaging methods. We first introduce effective connectivity and discuss the mechanisms underlying CCEP generation. Next, we highlight how CCEP mapping has begun to provide insight into the neural basis of non-invasive imaging signals. Finally, we present a novel approach to perturbing and measuring brain network function during cognitive processing. The direct measurement of CCEPs in response to electrical stimulation represents a potentially powerful clinical and basic science tool for probing the large-scale networks of the human cerebral cortex. PMID:25180306

  19. Hypnosis and imaging of the living human brain.

    Science.gov (United States)

    Landry, Mathieu; Raz, Amir

    2015-01-01

    Over more than two decades, studies using imaging techniques of the living human brain have begun to explore the neural correlates of hypnosis. The collective findings provide a gripping, albeit preliminary, account of the underlying neurobiological mechanisms involved in hypnotic phenomena. While substantial advances lend support to different hypotheses pertaining to hypnotic modulation of attention, control, and monitoring processes, the complex interactions among the many mediating variables largely hinder our ability to isolate robust commonalities across studies. The present account presents a critical integrative synthesis of neuroimaging studies targeting hypnosis as a function of suggestion. Specifically, hypnotic induction without task-specific suggestion is examined, as well as suggestions concerning sensation and perception, memory, and ideomotor response. The importance of carefully designed experiments is highlighted to better tease apart the neural correlates that subserve hypnotic phenomena. Moreover, converging findings intimate that hypnotic suggestions seem to induce specific neural patterns. These observations propose that suggestions may have the ability to target focal brain networks. Drawing on evidence spanning several technological modalities, neuroimaging studies of hypnosis pave the road to a more scientific understanding of a dramatic, yet largely evasive, domain of human behavior.

  20. Long distance communication in the human brain: timing constraints for inter-hemispheric synchrony and the origin of brain lateralization

    Directory of Open Access Journals (Sweden)

    FRANCISCO ABOITIZ

    2003-01-01

    Full Text Available Analysis of corpus callosum fiber composition reveals that inter-hemispheric transmission time may put constraints on the development of inter-hemispheric synchronic ensembles, especially in species with large brains like humans. In order to overcome this limitation, a subset of large-diameter callosal fibers are specialized for fast inter-hemispheric transmission, particularly in large-brained species. Nevertheless, the constraints on fast inter-hemispheric communication in large-brained species can somehow contribute to the development of ipsilateral, intrahemispheric networks, which might promote the development of brain lateralization.

  1. Ghrelin modulates encoding-related brain function without enhancing memory formation in humans.

    Science.gov (United States)

    Kunath, N; Müller, N C J; Tonon, M; Konrad, B N; Pawlowski, M; Kopczak, A; Elbau, I; Uhr, M; Kühn, S; Repantis, D; Ohla, K; Müller, T D; Fernández, G; Tschöp, M; Czisch, M; Steiger, A; Dresler, M

    2016-11-15

    Ghrelin regulates energy homeostasis in various species and enhances memory in rodent models. In humans, the role of ghrelin in cognitive processes has yet to be characterized. Here we show in a double-blind randomized crossover design that acute administration of ghrelin alters encoding-related brain activity, however does not enhance memory formation in humans. Twenty-one healthy young male participants had to memorize food- and non-food-related words presented on a background of a virtual navigational route while undergoing fMRI recordings. After acute ghrelin administration, we observed decreased post-encoding resting state fMRI connectivity between the caudate nucleus and the insula, amygdala, and orbitofrontal cortex. In addition, brain activity related to subsequent memory performance was modulated by ghrelin. On the next day, however, no differences were found in free word recall or cued location-word association recall between conditions; and ghrelin's effects on brain activity or functional connectivity were unrelated to memory performance. Further, ghrelin had no effect on a cognitive test battery comprising tests for working memory, fluid reasoning, creativity, mental speed, and attention. In conclusion, in contrast to studies with animal models, we did not find any evidence for the potential of ghrelin acting as a short-term cognitive enhancer in humans. Copyright © 2016 Elsevier Inc. All rights reserved.

  2. Gaze-and-brain-controlled interfaces for human-computer and human-robot interaction

    Directory of Open Access Journals (Sweden)

    Shishkin S. L.

    2017-09-01

    Full Text Available Background. Human-machine interaction technology has greatly evolved during the last decades, but manual and speech modalities remain single output channels with their typical constraints imposed by the motor system’s information transfer limits. Will brain-computer interfaces (BCIs and gaze-based control be able to convey human commands or even intentions to machines in the near future? We provide an overview of basic approaches in this new area of applied cognitive research. Objective. We test the hypothesis that the use of communication paradigms and a combination of eye tracking with unobtrusive forms of registering brain activity can improve human-machine interaction. Methods and Results. Three groups of ongoing experiments at the Kurchatov Institute are reported. First, we discuss the communicative nature of human-robot interaction, and approaches to building a more e cient technology. Specifically, “communicative” patterns of interaction can be based on joint attention paradigms from developmental psychology, including a mutual “eye-to-eye” exchange of looks between human and robot. Further, we provide an example of “eye mouse” superiority over the computer mouse, here in emulating the task of selecting a moving robot from a swarm. Finally, we demonstrate a passive, noninvasive BCI that uses EEG correlates of expectation. This may become an important lter to separate intentional gaze dwells from non-intentional ones. Conclusion. The current noninvasive BCIs are not well suited for human-robot interaction, and their performance, when they are employed by healthy users, is critically dependent on the impact of the gaze on selection of spatial locations. The new approaches discussed show a high potential for creating alternative output pathways for the human brain. When support from passive BCIs becomes mature, the hybrid technology of the eye-brain-computer (EBCI interface will have a chance to enable natural, fluent, and the

  3. Fitted hyperelastic parameters for Human brain tissue from reported tension, compression, and shear tests.

    Science.gov (United States)

    Moran, Richard; Smith, Joshua H; García, José J

    2014-11-28

    The mechanical properties of human brain tissue are the subject of interest because of their use in understanding brain trauma and in developing therapeutic treatments and procedures. To represent the behavior of the tissue, we have developed hyperelastic mechanical models whose parameters are fitted in accordance with experimental test results. However, most studies available in the literature have fitted parameters with data of a single type of loading, such as tension, compression, or shear. Recently, Jin et al. (Journal of Biomechanics 46:2795-2801, 2013) reported data from ex vivo tests of human brain tissue under tension, compression, and shear loading using four strain rates and four different brain regions. However, they do not report parameters of energy functions that can be readily used in finite element simulations. To represent the tissue behavior for the quasi-static loading conditions, we aimed to determine the best fit of the hyperelastic parameters of the hyperfoam, Ogden, and polynomial strain energy functions available in ABAQUS for the low strain rate data, while simultaneously considering all three loading modes. We used an optimization process conducted in MATLAB, calling iteratively three finite element models developed in ABAQUS that represent the three loadings. Results showed a relatively good fit to experimental data in all loading modes using two terms in the energy functions. Values for the shear modulus obtained in this analysis (897-1653Pa) are in the range of those presented in other studies. These energy-function parameters can be used in brain tissue simulations using finite element models. Copyright © 2014 Elsevier Ltd. All rights reserved.

  4. Reptiles: a new model for brain evo-devo research.

    Science.gov (United States)

    Nomura, Tadashi; Kawaguchi, Masahumi; Ono, Katsuhiko; Murakami, Yasunori

    2013-03-01

    Vertebrate brains exhibit vast amounts of anatomical diversity. In particular, the elaborate and complex nervous system of amniotes is correlated with the size of their behavioral repertoire. However, the evolutionary mechanisms underlying species-specific brain morphogenesis remain elusive. In this review we introduce reptiles as a new model organism for understanding brain evolution. These animal groups inherited ancestral traits of brain architectures. We will describe several unique aspects of the reptilian nervous system with a special focus on the telencephalon, and discuss the genetic mechanisms underlying reptile-specific brain morphology. The establishment of experimental evo-devo approaches to studying reptiles will help to shed light on the origin of the amniote brains. Copyright © 2013 Wiley Periodicals, Inc.

  5. BDNF Val66met and 5-HTTLPR polymorphisms predict a human in vivo marker for brain serotonin levels

    DEFF Research Database (Denmark)

    Fisher, Patrick M; Holst, Klaus K; Adamsen, Dea

    2015-01-01

    ) polymorphism. We applied a linear latent variable model (LVM) using regional 5-HT4 binding values (neocortex, amygdala, caudate, hippocampus, and putamen) from 68 healthy humans, allowing us to explicitly model brain-wide and region-specific genotype effects on 5-HT4 binding. Our data supported an LVM wherein...... specifically affects 5-HT4 binding in the neocortex. These findings implicate serotonin signaling as an important molecular mediator underlying the effects of BDNF val66met and 5-HTTLPR on behavior and related risk for neuropsychiatric illness in humans. Hum Brain Mapp, 2014. © 2014 Wiley Periodicals, Inc....

  6. Differences in distribution and regulation of astrocytic aquaporin-4 in human and rat hydrocephalic brain

    DEFF Research Database (Denmark)

    Skjolding, Anders Daehli; Holst, Anders Vedel; Broholm, Helle

    2013-01-01

    findings to human pathophysiology. This study compares expression of aquaporin-4 in hydrocephalic human brain with human controls and hydrocephalic rat brain. Methods:  Cortical biopsies from patients with chronic hydrocephalus (n=29) were sampled secondary to planned surgical intervention. Aquaporin-4...

  7. Multistability in Large Scale Models of Brain Activity.

    Directory of Open Access Journals (Sweden)

    Mathieu Golos

    2015-12-01

    Full Text Available Noise driven exploration of a brain network's dynamic repertoire has been hypothesized to be causally involved in cognitive function, aging and neurodegeneration. The dynamic repertoire crucially depends on the network's capacity to store patterns, as well as their stability. Here we systematically explore the capacity of networks derived from human connectomes to store attractor states, as well as various network mechanisms to control the brain's dynamic repertoire. Using a deterministic graded response Hopfield model with connectome-based interactions, we reconstruct the system's attractor space through a uniform sampling of the initial conditions. Large fixed-point attractor sets are obtained in the low temperature condition, with a bigger number of attractors than ever reported so far. Different variants of the initial model, including (i a uniform activation threshold or (ii a global negative feedback, produce a similarly robust multistability in a limited parameter range. A numerical analysis of the distribution of the attractors identifies spatially-segregated components, with a centro-medial core and several well-delineated regional patches. Those different modes share similarity with the fMRI independent components observed in the "resting state" condition. We demonstrate non-stationary behavior in noise-driven generalizations of the models, with different meta-stable attractors visited along the same time course. Only the model with a global dynamic density control is found to display robust and long-lasting non-stationarity with no tendency toward either overactivity or extinction. The best fit with empirical signals is observed at the edge of multistability, a parameter region that also corresponds to the highest entropy of the attractors.

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

    Science.gov (United States)

    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.

  9. Modeling cognition and disease using human glial chimeric mice.

    Science.gov (United States)

    Goldman, Steven A; Nedergaard, Maiken; Windrem, Martha S

    2015-08-01

    As new methods for producing and isolating human glial progenitor cells (hGPCs) have been developed, the disorders of myelin have become especially compelling targets for cell-based therapy. Yet as animal modeling of glial progenitor cell-based therapies has progressed, it has become clear that transplanted hGPCs not only engraft and expand within murine hosts, but dynamically outcompete the resident progenitors so as to ultimately dominate the host brain. The engrafted human progenitor cells proceed to generate parenchymal astrocytes, and when faced with a hypomyelinated environment, oligodendrocytes as well. As a result, the recipient brains may become inexorably humanized with regards to their resident glial populations, yielding human glial chimeric mouse brains. These brains provide us a fundamentally new tool by which to assess the species-specific attributes of glia in modulating human cognition and information processing. In addition, the cellular humanization of these brains permits their use in studying glial infectious and inflammatory disorders unique to humans, and the effects of those disorders on the glial contributions to cognition. Perhaps most intriguingly, by pairing our ability to construct human glial chimeras with the production of patient-specific hGPCs derived from pluripotential stem cells, we may now establish mice in which a substantial proportion of resident glia are both human and disease-derived. These mice in particular may provide us new opportunities for studying the human-specific contributions of glia to psychopathology, as well as to higher cognition. As such, the assessment of human glial chimeric mice may provide us new insight into the species-specific contributions of glia to human cognitive evolution, as well as to the pathogenesis of human neurological and neuropsychiatric disease. © 2015 Wiley Periodicals, Inc.

  10. Resolving Anatomical and Functional Structure in Human Brain Organization: Identifying Mesoscale Organization in Weighted Network Representations

    Science.gov (United States)

    Lohse, Christian; Bassett, Danielle S.; Lim, Kelvin O.; Carlson, Jean M.

    2014-01-01

    Human brain anatomy and function display a combination of modular and hierarchical organization, suggesting the importance of both cohesive structures and variable resolutions in the facilitation of healthy cognitive processes. However, tools to simultaneously probe these features of brain architecture require further development. We propose and apply a set of methods to extract cohesive structures in network representations of brain connectivity using multi-resolution techniques. We employ a combination of soft thresholding, windowed thresholding, and resolution in community detection, that enable us to identify and isolate structures associated with different weights. One such mesoscale structure is bipartivity, which quantifies the extent to which the brain is divided into two partitions with high connectivity between partitions and low connectivity within partitions. A second, complementary mesoscale structure is modularity, which quantifies the extent to which the brain is divided into multiple communities with strong connectivity within each community and weak connectivity between communities. Our methods lead to multi-resolution curves of these network diagnostics over a range of spatial, geometric, and structural scales. For statistical comparison, we contrast our results with those obtained for several benchmark null models. Our work demonstrates that multi-resolution diagnostic curves capture complex organizational profiles in weighted graphs. We apply these methods to the identification of resolution-specific characteristics of healthy weighted graph architecture and altered connectivity profiles in psychiatric disease. PMID:25275860

  11. Fresh Frozen Plasma Modulates Brain Gene Expression in a Swine Model of Traumatic Brain Injury and Shock

    DEFF Research Database (Denmark)

    Sillesen, Martin; Bambakidis, Ted; Dekker, Simone E

    2017-01-01

    BACKGROUND: Resuscitation with fresh frozen plasma (FFP) decreases brain lesion size and swelling in a swine model of traumatic brain injury and hemorrhagic shock. We hypothesized that brain gene expression profiles after traumatic brain injury and hemorrhagic shock would be modulated by FFP resu...

  12. A digital interactive human brain atlas based on Chinese visible human datasets for anatomy teaching.

    Science.gov (United States)

    Li, Qiyu; Ran, Xu; Zhang, Shaoxiang; Tan, Liwen; Qiu, Mingguo

    2014-01-01

    As we know, the human brain is one of the most complicated organs in the human body, which is the key and difficult point in neuroanatomy and sectional anatomy teaching. With the rapid development and extensive application of imaging technology in clinical diagnosis, doctors are facing higher and higher requirement on their anatomy knowledge. Thus, to cultivate medical students to meet the needs of medical development today and to improve their ability to read and understand radiographic images have become urgent challenges for the medical teachers. In this context, we developed a digital interactive human brain atlas based on the Chinese visible human datasets for anatomy teaching (available for free download from http://www.chinesevisiblehuman.com/down/DHBA.rar). The atlas simultaneously provides views in all 3 primary planes of section. The main structures of the human brain have been anatomically labeled in all 3 views. It is potentially useful for anatomy browsing, user self-testing, and automatic student assessment. In a word, it is interactive, 3D, user friendly, and free of charge, which can provide a new, intuitive means for anatomy teaching.

  13. Using induced pluripotent stem cells derived neurons to model brain diseases

    Directory of Open Access Journals (Sweden)

    Cindy E McKinney

    2017-01-01

    Full Text Available The ability to use induced pluripotent stem cells (iPSC to model brain diseases is a powerful tool for unraveling mechanistic alterations in these disorders. Rodent models of brain diseases have spurred understanding of pathology but the concern arises that they may not recapitulate the full spectrum of neuron disruptions associated with human neuropathology. iPSC derived neurons, or other neural cell types, provide the ability to access pathology in cells derived directly from a patient's blood sample or skin biopsy where availability of brain tissue is limiting. Thus, utilization of iPSC to study brain diseases provides an unlimited resource for disease modelling but may also be used for drug screening for effective therapies and may potentially be used to regenerate aged or damaged cells in the future. Many brain diseases across the spectrum of neurodevelopment, neurodegenerative and neuropsychiatric are being approached by iPSC models. The goal of an iPSC based disease model is to identify a cellular phenotype that discriminates the disease-bearing cells from the control cells. In this mini-review, the importance of iPSC cell models validated for pluripotency, germline competency and function assessments is discussed. Selected examples for the variety of brain diseases that are being approached by iPSC technology to discover or establish the molecular basis of the neuropathology are discussed.

  14. Serotonin 2A receptor agonist binding in the human brain with [C]Cimbi-36

    DEFF Research Database (Denmark)

    Ettrup, A.; da Cunha-Bang, S.; McMahon, Barry P.

    2014-01-01

    [C]Cimbi-36 was recently developed as a selective serotonin 2A (5-HT) receptor agonist radioligand for positron emission tomography (PET) brain imaging. Such an agonist PET radioligand may provide a novel, and more functional, measure of the serotonergic system and agonist binding is more likely ....... Thus, we here describe [C]Cimbi-36 as the first agonist PET radioligand to successfully image and quantify 5-HT receptors in the human brain.Journal of Cerebral Blood Flow & Metabolism advance online publication, 30 April 2014; doi:10.1038/jcbfm.2014.68.......[C]Cimbi-36 was recently developed as a selective serotonin 2A (5-HT) receptor agonist radioligand for positron emission tomography (PET) brain imaging. Such an agonist PET radioligand may provide a novel, and more functional, measure of the serotonergic system and agonist binding is more likely...... than antagonist binding to reflect 5-HT levels in vivo. Here, we show data from a first-in-human clinical trial with [C]Cimbi-36. In 29 healthy volunteers, we found high brain uptake and distribution according to 5-HT receptors with [C]Cimbi-36 PET. The two-tissue compartment model using arterial input...

  15. Neuroanatomical abnormalities in chronic tinnitus in the human brain

    Science.gov (United States)

    Adjamian, Peyman; Hall, Deborah A.; Palmer, Alan R.; Allan, Thomas W.; Langers, Dave R.M.

    2014-01-01

    In this paper, we review studies that have investigated brain morphology in chronic tinnitus in order to better understand the underlying pathophysiology of the disorder. Current consensus is that tinnitus is a disorder involving a distributed network of peripheral and central pathways in the nervous system. However, the precise mechanism remains elusive and it is unclear which structures are involved. Given that brain structure and function are highly related, identification of anatomical differences may shed light upon the mechanism of tinnitus generation and maintenance. We discuss anatomical changes in the auditory cortex, the limbic system, and prefrontal cortex, among others. Specifically, we discuss the gating mechanism of tinnitus and evaluate the evidence in support of the model from studies of brain anatomy. Although individual studies claim significant effects related to tinnitus, outcomes are divergent and even contradictory across studies. Moreover, results are often confounded by the presence of hearing loss. We conclude that, at present, the overall evidence for structural abnormalities specifically related to tinnitus is poor. As this area of research is expanding, we identify some key considerations for research design and propose strategies for future research. PMID:24892904

  16. Reactive astrocytes associated with plaques in TgCRND8 mouse brain and in human Alzheimer brain express phosphoprotein enriched in astrocytes (PEA-15).

    Science.gov (United States)

    Thomason, Lynsie A M; Smithson, Laura J; Hazrati, Lili-Naz; McLaurin, JoAnne; Kawaja, Michael D

    2013-08-02

    To identify potential biomarkers associated with Alzheimer's disease (AD)-like neuropathologies in the murine brain, we conducted proteomic analyses of neocortices from TgCRND8 mice. Here we found that phosphoprotein enriched in astrocytes 15 kDa (PEA-15) is expressed at higher levels in the neocortical proteomes from 6-month old TgCRND8 mice, as compared to non-transgenic mice. Immunostaining for PEA-15 revealed reactive astrocytes associated with the neocortical amyloid plaques in TgCRND8 mice and in post-mortem human AD brains. This is the first report of increased phosphoprotein enriched in astrocytes (PEA-15) expression in reactive astrocytes of an AD mouse model and human AD brains. Copyright © 2013 Federation of European Biochemical Societies. Published by Elsevier B.V. All rights reserved.

  17. Controlling ferrofluid permeability across the blood-brain barrier model

    Science.gov (United States)

    Shi, Di; Sun, Linlin; Mi, Gujie; Sheikh, Lubna; Bhattacharya, Soumya; Nayar, Suprabha; Webster, Thomas J.

    2014-02-01

    In the present study, an in vitro blood-brain barrier model was developed using murine brain endothelioma cells (b.End3 cells). Confirmation of the blood-brain barrier model was completed by examining the permeability of FITC-Dextran at increasing exposure times up to 96 h in serum-free medium and comparing such values with values from the literature. After such confirmation, the permeability of five novel ferrofluid (FF) nanoparticle samples, GGB (ferrofluids synthesized using glycine, glutamic acid and BSA), GGC (glycine, glutamic acid and collagen), GGP (glycine, glutamic acid and PVA), BPC (BSA, PEG and collagen) and CPB (collagen, PVA and BSA), was determined using this blood-brain barrier model. All of the five FF samples were characterized by zeta potential to determine their charge as well as TEM and dynamic light scattering for determining their hydrodynamic diameter. Results showed that FF coated with collagen passed more easily through the blood-brain barrier than FF coated with glycine and glutamic acid based on an increase of 4.5% in permeability. Through such experiments, diverse magnetic nanomaterials (such as FF) were identified for: (1) MRI use since they were less permeable to penetrate the blood-brain barrier to avoid neural tissue toxicity (e.g. GGB) or (2) brain drug delivery since they were more permeable to the blood-brain barrier (e.g. CPB).

  18. Deep brain stimulation, brain maps and personalized medicine: lessons from the human genome project.

    Science.gov (United States)

    Fins, Joseph J; Shapiro, Zachary E

    2014-01-01

    Although the appellation of personalized medicine is generally attributed to advanced therapeutics in molecular medicine, deep brain stimulation (DBS) can also be so categorized. Like its medical counterpart, DBS is a highly personalized intervention that needs to be tailored to a patient's individual anatomy. And because of this, DBS like more conventional personalized medicine, can be highly specific where the object of care is an N = 1. But that is where the similarities end. Besides their differing medical and surgical provenances, these two varieties of personalized medicine have had strikingly different impacts. The molecular variant, though of a more recent vintage has thrived and is experiencing explosive growth, while DBS still struggles to find a sustainable therapeutic niche. Despite its promise, and success as a vetted treatment for drug resistant Parkinson's Disease, DBS has lagged in broadening its development, often encountering regulatory hurdles and financial barriers necessary to mount an adequate number of quality trials. In this paper we will consider why DBS-or better yet neuromodulation-has encountered these challenges and contrast this experience with the more successful advance of personalized medicine. We will suggest that personalized medicine and DBS's differential performance can be explained as a matter of timing and complexity. We believe that DBS has struggled because it has been a journey of scientific exploration conducted without a map. In contrast to molecular personalized medicine which followed the mapping of the human genome and the Human Genome Project, DBS preceded plans for the mapping of the human brain. We believe that this sequence has given personalized medicine a distinct advantage and that the fullest potential of DBS will be realized both as a cartographical or electrophysiological probe and as a modality of personalized medicine.

  19. Novel brain arteriovenous malformation mouse models for type 1 hereditary hemorrhagic telangiectasia.

    Directory of Open Access Journals (Sweden)

    Eun-Jung Choi

    Full Text Available Endoglin (ENG is a causative gene of type 1 hereditary hemorrhagic telangiectasia (HHT1. HHT1 patients have a higher prevalence of brain arteriovenous malformation (AVM than the general population and patients with other HHT subtypes. The pathogenesis of brain AVM in HHT1 patients is currently unknown and no specific medical therapy is available to treat patients. Proper animal models are crucial for identifying the underlying mechanisms for brain AVM development and for testing new therapies. However, creating HHT1 brain AVM models has been quite challenging because of difficulties related to deleting Eng-floxed sequence in Eng(2fl/2fl mice. To create an HHT1 brain AVM mouse model, we used several Cre transgenic mouse lines to delete Eng in different cell-types in Eng(2fl/2fl mice: R26CreER (all cell types after tamoxifen treatment, SM22α-Cre (smooth muscle and endothelial cell and LysM-Cre (lysozyme M-positive macrophage. An adeno-associated viral vector expressing vascular endothelial growth factor (AAV-VEGF was injected into the brain to induce focal angiogenesis. We found that SM22α-Cre-mediated Eng deletion in the embryo caused AVMs in the postnatal brain, spinal cord, and intestines. Induction of Eng deletion in adult mice using R26CreER plus local VEGF stimulation induced the brain AVM phenotype. In both models, Eng-null endothelial cells were detected in the brain AVM lesions, and formed mosaicism with wildtype endothelial cells. However, LysM-Cre-mediated Eng deletion in the embryo did not cause AVM in the postnatal brain even after VEGF stimulation. In this study, we report two novel HHT1 brain AVM models that mimic many phenotypes of human brain AVM and can thus be used for studying brain AVM pathogenesis and testing new therapies. Further, our data indicate that macrophage Eng deletion is insufficient and that endothelial Eng homozygous deletion is required for HHT1 brain AVM development.

  20. New neurons for injured brains? The emergence of new genetic model organisms to study brain regeneration.

    Science.gov (United States)

    Fernández-Hernández, Ismael; Rhiner, Christa

    2015-09-01

    Neuronal circuits in the adult brain have long been viewed as static and stable. However, research in the past 20 years has shown that specialized regions of the adult brain, which harbor adult neural stem cells, continue to produce new neurons in a wide range of species. Brain plasticity is also observed after injury. Depending on the extent and permissive environment of neurogenic regions, different organisms show great variability in their capacity to replace lost neurons by endogenous neurogenesis. In Zebrafish and Drosophila, the formation of new neurons from progenitor cells in the adult brain was only discovered recently. Here, we compare properties of adult neural stem cells, their niches and regenerative responses from mammals to flies. Current models of brain injury have revealed that specific injury-induced genetic programs and comparison of neuronal fitness are implicated in brain repair. We highlight the potential of these recently implemented models of brain regeneration to identify novel regulators of stem cell activation and regenerative neurogenesis. Copyright © 2015 Elsevier Ltd. All rights reserved.

  1. Understanding the mechanisms of familiar voice-identity recognition in the human brain.

    Science.gov (United States)

    Maguinness, Corrina; Roswandowitz, Claudia; Von Kriegstein, Katharina

    2018-03-31

    Humans have a remarkable skill for voice-identity recognition: most of us can remember many voices that surround us as 'unique'. In this review, we explore the computational and neural mechanisms which may support our ability to represent and recognise a unique voice-identity. We examine the functional architecture of voice-sensitive regions in the superior temporal gyrus/sulcus, and bring together findings on how these regions may interact with each other, and additional face-sensitive regions, to support voice-identity processing. We also contrast findings from studies on neurotypicals and clinical populations which have examined the processing of familiar and unfamiliar voices. Taken together, the findings suggest that representations of familiar and unfamiliar voices might dissociate in the human brain. Such an observation does not fit well with current models for voice-identity processing, which by-and-large assume a common sequential analysis of the incoming voice signal, regardless of voice familiarity. We provide a revised audio-visual integrative model of voice-identity processing which brings together traditional and prototype models of identity processing. This revised model includes a mechanism of how voice-identity representations are established and provides a novel framework for understanding and examining the potential differences in familiar and unfamiliar voice processing in the human brain. Copyright © 2018. Published by Elsevier Ltd.

  2. Brain repair after stroke—a novel neurological model

    OpenAIRE

    Small, Steven L.; Buccino, Giovanni; Solodkin, Ana

    2013-01-01

    Following stroke, patients are commonly left with debilitating motor and speech impairments. This article reviews the state of the art in neurological repair for stroke and proposes a new model for the future. We suggest that stroke treatment—from the time of the ictus itself to living with the consequences—must be fundamentally neurological, from limiting the extent of injury at the outset, to repairing the consequent damage. Our model links brain and behaviour by targeting brain circuits, a...

  3. Monte Carlo and phantom study in the brain edema models

    Directory of Open Access Journals (Sweden)

    Yubing Liu

    2017-05-01

    Full Text Available Because the brain edema has a crucial impact on morbidity and mortality, it is important to develop a noninvasive method to monitor the process of the brain edema effectively. When the brain edema occurs, the optical properties of the brain will change. The goal of this study is to access the feasibility and reliability of using noninvasive near-infrared spectroscopy (NIRS monitoring method to measure the brain edema. Specifically, three models, including the water content changes in the cerebrospinal fluid (CSF, gray matter and white matter, were explored. Moreover, these models were numerically simulated by the Monte Carlo studies. Then, the phantom experiments were performed to investigate the light intensity which was measured at different detecting radius on the tissue surface. The results indicated that the light intensity correlated well with the conditions of the brain edema and the detecting radius. Briefly, at the detecting radius of 3.0cm and 4.0cm, the light intensity has a high response to the change of tissue parameters and optical properties. Thus, it is possible to monitor the brain edema noninvasively by NIRS method and the light intensity is a reliable and simple parameter to assess the brain edema.

  4. Brain-to-brain hyperclassification reveals action-specific motor mapping of observed actions in humans.

    Science.gov (United States)

    Smirnov, Dmitry; Lachat, Fanny; Peltola, Tomi; Lahnakoski, Juha M; Koistinen, Olli-Pekka; Glerean, Enrico; Vehtari, Aki; Hari, Riitta; Sams, Mikko; Nummenmaa, Lauri

    2017-01-01

    Seeing an action may activate the corresponding action motor code in the observer. It remains unresolved whether seeing and performing an action activates similar action-specific motor codes in the observer and the actor. We used novel hyperclassification approach to reveal shared brain activation signatures of action execution and observation in interacting human subjects. In the first experiment, two "actors" performed four types of hand actions while their haemodynamic brain activations were measured with 3-T functional magnetic resonance imaging (fMRI). The actions were videotaped and shown to 15 "observers" during a second fMRI experiment. Eleven observers saw the videos of one actor, and the remaining four observers saw the videos of the other actor. In a control fMRI experiment, one of the actors performed actions with closed eyes, and five new observers viewed these actions. Bayesian canonical correlation analysis was applied to functionally realign observers' and actors' fMRI data. Hyperclassification of the seen actions was performed with Bayesian logistic regression trained on actors' data and tested with observers' data. Without the functional realignment, between-subjects accuracy was at chance level. With the realignment, the accuracy increased on average by 15 percentage points, exceeding both the chance level and the accuracy without functional realignment. The highest accuracies were observed in occipital, parietal and premotor cortices. Hyperclassification exceeded chance level also when the actor did not see her own actions. We conclude that the functional brain activation signatures underlying action execution and observation are partly shared, yet these activation signatures may be anatomically misaligned across individuals.

  5. Brain-to-brain hyperclassification reveals action-specific motor mapping of observed actions in humans.

    Directory of Open Access Journals (Sweden)

    Dmitry Smirnov

    Full Text Available Seeing an action may activate the corresponding action motor code in the observer. It remains unresolved whether seeing and performing an action activates similar action-specific motor codes in the observer and the actor. We used novel hyperclassification approach to reveal shared brain activation signatures of action execution and observation in interacting human subjects. In the first experiment, two "actors" performed four types of hand actions while their haemodynamic brain activations were measured with 3-T functional magnetic resonance imaging (fMRI. The actions were videotaped and shown to 15 "observers" during a second fMRI experiment. Eleven observers saw the videos of one actor, and the remaining four observers saw the videos of the other actor. In a control fMRI experiment, one of the actors performed actions with closed eyes, and five new observers viewed these actions. Bayesian canonical correlation analysis was applied to functionally realign observers' and actors' fMRI data. Hyperclassification of the seen actions was performed with Bayesian logistic regression trained on actors' data and tested with observers' data. Without the functional realignment, between-subjects accuracy was at chance level. With the realignment, the accuracy increased on average by 15 percentage points, exceeding both the chance level and the accuracy without functional realignment. The highest accuracies were observed in occipital, parietal and premotor cortices. Hyperclassification exceeded chance level also when the actor did not see her own actions. We conclude that the functional brain activation signatures underlying action execution and observation are partly shared, yet these activation signatures may be anatomically misaligned across individuals.

  6. Motor Skill Acquisition Promotes Human Brain Myelin Plasticity

    Directory of Open Access Journals (Sweden)

    Bimal Lakhani

    2016-01-01

    Full Text Available Experience-dependent structural changes are widely evident in gray matter. Using diffusion weighted imaging (DWI, the neuroplastic effect of motor training on white matter in the brain has been demonstrated. However, in humans it is not known whether specific features of white matter relate to motor skill acquisition or if these structural changes are associated to functional network connectivity. Myelin can be objectively quantified in vivo and used to index specific experience-dependent change. In the current study, seventeen healthy young adults completed ten sessions of visuomotor skill training (10,000 total movements using the right arm. Multicomponent relaxation imaging was performed before and after training. Significant increases in myelin water fraction, a quantitative measure of myelin, were observed in task dependent brain regions (left intraparietal sulcus [IPS] and left parieto-occipital sulcus. In addition, the rate of motor skill acquisition and overall change in myelin water fraction in the left IPS were negatively related, suggesting that a slower rate of learning resulted in greater neuroplastic change. This study provides the first evidence for experience-dependent changes in myelin that are associated with changes in skilled movements in healthy young adults.

  7. Human brain activity with near-infrared spectroscopy

    Science.gov (United States)

    Luo, Qingming; Chance, Britton

    1999-09-01

    Human brain activity was studied with a real time functional Near-InfraRed Imager (fNIRI). The imager has 16 measurement channels and covers 4 cm by 9 cm detection area. Brain activities in occipital, motor and prefrontal area were studied with the fNIRI. In prefrontal stimulation, language cognition, analogies, forming memory for new associations, emotional thinking, and mental arithmetic were carried out. Experimental results measured with fNIRI are demonstrated in this paper. It was shown that fNIRI technique is able to reveal the occipital activity during visual stimulation, and co-register well with results of fMRI in the motor cortex activity during finger tapping. In the studies of the effects of left prefrontal lobe on forming memory for new associations, it is shown that left prefrontal lobe activated more under deep conditions than that under shallow encoding, especially the dorsal part. In the studies of emotional thinking, it was shown that the responses were different between positive- negative emotional thinking and negative-positive emotional thinking. In mental arithmetic studies, higher activation was found in the first task than in the second, regardless of the difficulty, and higher activation was measured in subtraction of 17 than in subtraction of 3.

  8. Local infusion of Staphylococcus aureus into the porcine internal carotid artery as a model of sepsis-related brain abscesses - A pilot study

    DEFF Research Database (Denmark)

    Astrup, Lærke B.; Iburg, Tine M.; Agerholm, Jørgen S.

    2017-01-01

    Brain pathology is an important aspect of human sepsis but is difficult to study in human patients. Th erefore, animal models of sepsis-related brain pathology are needed. As pigs mirror multiple aspects of sepsis-related brain pathology in humans, this makes the pig a potentially suitable model....... Unfortunately, models of sepsis in pigs are difficult to manage due to the accompanying massive systemic inflammatory response. To overcome these difficulties we designed a model in pigs of brain bacteremia established by local brain infusion in order to evaluate if this approach could reduce the systemic...... responses but still reflect the brain pathology of sepsis in humans. As a pilot study to obtain basic knowledge, we evaluated two methods of local infusion: long term infusion (60 minutes) of Staphylococcus aureus suspended in saline and, short-term infusion (10 minutes) of S. aureus embedded in autologous...

  9. The brain's functional network architecture reveals human motives.

    Science.gov (United States)

    Hein, Grit; Morishima, Yosuke; Leiberg, Susanne; Sul, Sunhae; Fehr, Ernst

    2016-03-04

    Goal-directed human behaviors are driven by motives. Motives are, however, purely mental constructs that are not directly observable. Here, we show that the brain's functional network architecture captures information that predicts different motives behind the same altruistic act with high accuracy. In contrast, mere activity in these regions contains no information about motives. Empathy-based altruism is primarily characterized by a positive connectivity from the anterior cingulate cortex (ACC) to the anterior insula (AI), whereas reciprocity-based altruism additionally invokes strong positive connectivity from the AI to the ACC and even stronger positive connectivity from the AI to the ventral striatum. Moreover, predominantly selfish individuals show distinct functional architectures compared to altruists, and they only increase altruistic behavior in response to empathy inductions, but not reciprocity inductions. Copyright © 2016, American Association for the Advancement of Science.

  10. [Age and changes in human brain capillaries (histochemical study)].

    Science.gov (United States)

    Chertok, V M

    1985-02-01

    The vascular-capillary bed in the field 17 of the human brain cortex (from fetuses up to 86 years of age) has been studied by means of some histochemical methods to reveal alcaline phosphatase and Mg-ATPase. As demonstrate quantitative methods, active processes of the capillary bed formation in the cerebral cortex take place before 8-16 years of age. Towards the old age, the amount of the vessels with a high and moderate enzymatic activity decreases, but those with a low enzymatic activity increases. The average parameters of the optic density of the reaction product decreases respectively in the capillary wall, so does the intensity of metabolic processes, while the value of the working surface increases up to 75 years of age.

  11. The power of love on the human brain.

    Science.gov (United States)

    Bianchi-Demicheli, Francesco; Grafton, Scott T; Ortigue, Stephanie

    2006-01-01

    Romantic love has been the source for some of the greatest achievements of mankind throughout the ages. The recent localization of romantic love within subcortico-cortical reward, motivation and emotion systems in the human brain has suggested that love is a goal-directed drive with predictable facilitation effects on cognitive behavior, rather than a pure emotion. Here we show that the subliminal exposure of a beloved's name (romantic prime) during a lexical decision task dramatically improves performance in women in love (Experiment 1), as the subliminal presentation of a passion's descriptive noun does (Experiment 2). The parallel between love and passion allows us to interpret these facilitation effects as corresponding to cognitive top-down processes within a motivation-enhanced neural network.

  12. Role of synchronized oscillatory brain activity for human pain perception.

    Science.gov (United States)

    Hauck, Michael; Lorenz, Jürgen; Engel, Andreas K

    2008-01-01

    The understanding of cortical pain processing in humans has significantly improved since the development of modern neuroimaging techniques. Non-invasive electrophysiological approaches such as electro- and magnetoencephalography have proven to be helpful tools for the real-time investigation of neuronal signals and synchronous communication between cortical areas. In particular, time-frequency decomposition of signals recorded with these techniques seems to be a promising approach because different pain-related oscillatory changes can be observed within different frequency bands, which are likely to be linked to specific sensory and motor functions. In this review we discuss the latest evidence on pain-induced time-frequency signals and propose that changes in oscillatory activity reflect an essential communication mechanism in the brain that is modulated during pain processing. The importance of synchronization processes for normal and pathological pain processing, such as chronic pain states, is discussed.

  13. A MARKOV RANDOM FIELD-BASED APPROACH TO CHARACTERIZING HUMAN BRAIN DEVELOPMENT USING SPATIAL-TEMPORAL TRANSCRIPTOME DATA.

    Science.gov (United States)

    Lin, Zhixiang; Sanders, Stephan J; Li, Mingfeng; Sestan, Nenad; State, Matthew W; Zhao, Hongyu

    2015-03-01

    Human neurodevelopment is a highly regulated biological process. In this article, we study the dynamic changes of neurodevelopment through the analysis of human brain microarray data, sampled from 16 brain regions in 15 time periods of neurodevelopment. We develop a two-step inferential procedure to identify expressed and unexpressed genes and to detect differentially expressed genes between adjacent time periods. Markov Random Field (MRF) models are used to efficiently utilize the information embedded in brain region similarity and temporal dependency in our approach. We develop and implement a Monte Carlo expectation-maximization (MCEM) algorithm to estimate the model parameters. Simulation studies suggest that our approach achieves lower misclassification error and potential gain in power compared with models not incorporating spatial similarity and temporal dependency.

  14. Network dynamics with BrainX3: a large-scale simulation of the human brain network with real-time interaction

    Science.gov (United States)

    Arsiwalla, Xerxes D.; Zucca, Riccardo; Betella, Alberto; Martinez, Enrique; Dalmazzo, David; Omedas, Pedro; Deco, Gustavo; Verschure, Paul F. M. J.

    2015-01-01

    BrainX3 is a large-scale simulation of human brain activity with real-time interaction, rendered in 3D in a virtual reality environment, which combines computational power with human intuition for the exploration and analysis of complex dynamical networks. We ground this simulation on structural connectivity obtained from diffusion spectrum imaging data and model it on neuronal population dynamics. Users can interact with BrainX3 in real-time by perturbing brain regions with transient stimulations to observe reverberating network activity, simulate lesion dynamics or implement network analysis functions from a library of graph theoretic measures. BrainX3 can thus be used as a novel immersive platform for exploration and analysis of dynamical activity patterns in brain networks, both at rest or in a task-related state, for discovery of signaling pathways associated to brain function and/or dysfunction and as a tool for virtual neurosurgery. Our results demonstrate these functionalities and shed insight on the dynamics of the resting-state attractor. Specifically, we found that a noisy network seems to favor a low firing attractor state. We also found that the dynamics of a noisy network is less resilient to lesions. Our simulations on TMS perturbations show that even though TMS inhibits most of the network, it also sparsely excites a few regions. This is presumably due to anti-correlations in the dynamics and suggests that even a lesioned network can show sparsely distributed increased activity compared to healthy resting-state, over specific brain areas. PMID:25759649

  15. Network Dynamics with BrainX3: A Large-Scale Simulation of the Human Brain Network with Real-Time Interaction

    Directory of Open Access Journals (Sweden)

    Xerxes D. Arsiwalla

    2015-02-01

    Full Text Available BrainX3 is a large-scale simulation of human brain activity with real-time interaction, rendered in 3D in a virtual reality environment, which combines computational power with human intuition for the exploration and analysis of complex dynamical networks. We ground this simulation on structural connectivity obtained from diffusion spectrum imaging data and model it on neuronal population dynamics. Users can interact with BrainX3 in real-time by perturbing brain regions with transient stimulations to observe reverberating network activity, simulate lesion dynamics or implement network analysis functions from a library of graph theoretic measures. BrainX3 can thus be used as a novel immersive platform for real-time exploration and analysis of dynamical activity patterns in brain networks, both at rest or in a task-related state, for discovery of signaling pathways associated to brain function and/or dysfunction and as a tool for virtual neurosurgery. Our results demonstrate these functionalities and shed insight on the dynamics of the resting-state attractor. Specifically, we found that a noisy network seems to favor a low firing attractor state. We also found that the dynamics of a noisy network is less resilient to lesions. Our simulations on TMS perturbations show that even though TMS inhibits most of the network, it also sparsely excites a few regions. This is presumably, due to anti-correlations in the dynamics and suggests that even a lesioned network can show sparsely distributed increased activity compared to healthy resting-state, over specific brain areas.

  16. Network dynamics with BrainX(3): a large-scale simulation of the human brain network with real-time interaction.

    Science.gov (United States)

    Arsiwalla, Xerxes D; Zucca, Riccardo; Betella, Alberto; Martinez, Enrique; Dalmazzo, David; Omedas, Pedro; Deco, Gustavo; Verschure, Paul F M J

    2015-01-01

    BrainX(3) is a large-scale simulation of human brain activity with real-time interaction, rendered in 3D in a virtual reality environment, which combines computational power with human intuition for the exploration and analysis of complex dynamical networks. We ground this simulation on structural connectivity obtained from diffusion spectrum imaging data and model it on neuronal population dynamics. Users can interact with BrainX(3) in real-time by perturbing brain regions with transient stimulations to observe reverberating network activity, simulate lesion dynamics or implement network analysis functions from a library of graph theoretic measures. BrainX(3) can thus be used as a novel immersive platform for exploration and analysis of dynamical activity patterns in brain networks, both at rest or in a task-related state, for discovery of signaling pathways associated to brain function and/or dysfunction and as a tool for virtual neurosurgery. Our results demonstrate these functionalities and shed insight on the dynamics of the resting-state attractor. Specifically, we found that a noisy network seems to favor a low firing attractor state. We also found that the dynamics of a noisy network is less resilient to lesions. Our simulations on TMS perturbations show that even though TMS inhibits most of the network, it also sparsely excites a few regions. This is presumably due to anti-correlations in the dynamics and suggests that even a lesioned network can show sparsely distributed increased activity compared to healthy resting-state, over specific brain areas.

  17. Gorilla and Orangutan Brains Conform to the Primate Cellular Scaling Rules: Implications for Human Evolution

    Science.gov (United States)

    Herculano-Houzel, Suzana; Kaas, Jon H.

    2011-01-01

    Gorillas and orangutans are primates at least as large as humans, but their brains amount to about one third of the size of the human brain. This discrepancy has been used as evidence that the human brain is about 3 times larger than it should be for a primate species of its body size. In contrast to the view that the human brain is special in its size, we have suggested that it is the great apes that might have evolved bodies that are unusually large, on the basis of our recent finding that the cellular composition of the human brain matches that expected for a primate brain of its size, making the human brain a linearly scaled-up primate brain in its number of cells. To investigate whether the brain of great apes also conforms to the primate cellular scaling rules identified previously, we determine the numbers of neuronal and other cells that compose the orangutan and gorilla cerebella, use these numbers to calculate the size of the brain and of the cerebral cortex expected for these species, and show that these match the sizes described in the literature. Our results suggest that the brains of great apes also scale linearly in their numbers of neurons like other primate brains, including humans. The conformity of great apes and humans to the linear cellular scaling rules that apply to other primates that diverged earlier in primate evolution indicates that prehistoric Homo species as well as other hominins must have had brains that conformed to the same scaling rules, irrespective of their body size. We then used those scaling rules and published estimated brain volumes for various hominin species to predict the numbers of neurons that composed their brains. We predict that Homo heidelbergensis and Homo neanderthalensis had brains with approximately 80 billion neurons, within the range of variation found in modern Homo sapiens. We propose that while the cellular scaling rules that apply to the primate brain have remained stable in hominin evolution (since they

  18. “Messing with the mind”: evolutionary challenges to human brain augmentation

    Science.gov (United States)

    Saniotis, Arthur; Henneberg, Maciej; Kumaratilake, Jaliya; Grantham, James P.

    2014-01-01

    The issue of brain augmentation has received considerable scientific attention over the last two decades. A key factor to brain augmentation that has been widely overlooked are the complex evolutionary processes which have taken place in evolving the human brain to its current state of functioning. Like other bodily organs, the human brain has been subject to the forces of biological adaptation. The structure and function of the brain, is very complex and only now we are beginning to understand some of the basic concepts of cognition. Therefore, this article proposes that brain-machine interfacing and nootropics are not going to produce “augmented” brains because we do not understand enough about how evolutionary pressures have informed the neural networks which support human cognitive faculties. PMID:25324734

  19. Automatic segmentation of brain MRIs and mapping neuroanatomy across the human lifespan

    Science.gov (United States)

    Keihaninejad, Shiva; Heckemann, Rolf A.; Gousias, Ioannis S.; Rueckert, Daniel; Aljabar, Paul; Hajnal, Joseph V.; Hammers, Alexander

    2009-02-01

    A robust model for the automatic segmentation of human brain images into anatomically defined regions across the human lifespan would be highly desirable, but such structural segmentations of brain MRI are challenging due to age-related changes. We have developed a new method, based on established algorithms for automatic segmentation of young adults' brains. We used prior information from 30 anatomical atlases, which had been manually segmented into 83 anatomical structures. Target MRIs came from 80 subjects (~12 individuals/decade) from 20 to 90 years, with equal numbers of men, women; data from two different scanners (1.5T, 3T), using the IXI database. Each of the adult atlases was registered to each target MR image. By using additional information from segmentation into tissue classes (GM, WM and CSF) to initialise the warping based on label consistency similarity before feeding this into the previous normalised mutual information non-rigid registration, the registration became robust enough to accommodate atrophy and ventricular enlargement with age. The final segmentation was obtained by combination of the 30 propagated atlases using decision fusion. Kernel smoothing was used for modelling the structural volume changes with aging. Example linear correlation coefficients with age were, for lateral ventricular volume, rmale=0.76, rfemale=0.58 and, for hippocampal volume, rmale=-0.6, rfemale=-0.4 (allρ<0.01).

  20. Human mobility: Models and applications

    Science.gov (United States)

    Barbosa, Hugo; Barthelemy, Marc; Ghoshal, Gourab; James, Charlotte R.; Lenormand, Maxime; Louail, Thomas; Menezes, Ronaldo; Ramasco, José J.; Simini, Filippo; Tomasini, Marcello

    2018-03-01

    Recent years have witnessed an explosion of extensive geolocated datasets related to human movement, enabling scientists to quantitatively study individual and collective mobility patterns, and to generate models that can capture and reproduce the spatiotemporal structures and regularities in human trajectories. The study of human mobility is especially important for applications such as estimating migratory flows, traffic forecasting, urban planning, and epidemic modeling. In this survey, we review the approaches developed to reproduce various mobility patterns, with the main focus on recent developments. This review can be used both as an introduction to the fundamental modeling principles of human mobility, and as a collection of technical methods applicable to specific mobility-related problems. The review organizes the subject by differentiating between individual and population mobility and also between short-range and long-range mobility. Throughout the text the description of the theory is intertwined with real-world applications.

  1. Dynamics of the brain: Mathematical models and non-invasive experimental studies

    Science.gov (United States)

    Toronov, V.; Myllylä, T.; Kiviniemi, V.; Tuchin, V. V.

    2013-10-01

    Dynamics is an essential aspect of the brain function. In this article we review theoretical models of neural and haemodynamic processes in the human brain and experimental non-invasive techniques developed to study brain functions and to measure dynamic characteristics, such as neurodynamics, neurovascular coupling, haemodynamic changes due to brain activity and autoregulation, and cerebral metabolic rate of oxygen. We focus on emerging theoretical biophysical models and experimental functional neuroimaging results, obtained mostly by functional magnetic resonance imaging (fMRI) and near-infrared spectroscopy (NIRS). We also included our current results on the effects of blood pressure variations on cerebral haemodynamics and simultaneous measurements of fast processes in the brain by near-infrared spectroscopy and a very novel functional MRI technique called magnetic resonance encephalography. Based on a rapid progress in theoretical and experimental techniques and due to the growing computational capacities and combined use of rapidly improving and emerging neuroimaging techniques we anticipate during next decade great achievements in the overall knowledge of the human brain.

  2. Amyloid-β Dynamics Correlate with Neurological Status in the Injured Human Brain

    OpenAIRE

    Brody, David L.; Magnoni, Sandra; Schwetye, Kate E.; Spinner, Michael L.; Esparza, Thomas J.; Stocchetti, Nino; Zipfel, Gregory J.; Holtzman, David M.

    2008-01-01

    The amyloid-β peptide (Aβ) plays a central pathophysiological role in Alzheimer’s disease, but little is known about the concentration and dynamics of this secreted peptide in the extracellular space of the human brain. We used intracerebral microdialysis to obtain serial brain interstitial fluid (ISF) samples in 18 patients who were undergoing invasive intracranial monitoring after acute brain injury. We found a strong positive correlation between changes in brain ISF Aβ concentrations and n...

  3. A natural human hand model

    NARCIS (Netherlands)

    Van Nierop, O.A.; Van der Helm, A.; Overbeeke, K.J.; Djajadiningrat, T.J.P.

    2007-01-01

    We present a skeletal linked model of the human hand that has natural motion. We show how this can be achieved by introducing a new biology-based joint axis that simulates natural joint motion and a set of constraints that reduce an estimated 150 possible motions to twelve. The model is based on

  4. Development of a Model for Whole Brain Learning of Physiology

    Science.gov (United States)

    Eagleton, Saramarie; Muller, Anton

    2011-01-01

    In this report, a model was developed for whole brain learning based on Curry's onion model. Curry described the effect of personality traits as the inner layer of learning, information-processing styles as the middle layer of learning, and environmental and instructional preferences as the outer layer of learning. The model that was developed…

  5. First radiotherapy of human metastatic brain tumors delivered by a computerized tomography scanner (CTRx).

    Science.gov (United States)

    Rose, J H; Norman, A; Ingram, M; Aoki, C; Solberg, T; Mesa, A

    1999-12-01

    This Phase I study was designed to evaluate the computed tomography (CT) scanner as a device for radiation therapy of human brain tumors (CTRx). This first use in humans of a modified CT for treatment was founded on extensive research experience with canine tumors. An additional objective was to increase the therapeutic radiation dose to tumors compared to normal tissue by concentration of infused contrast material in tumors, an effect available at diagnostic x-ray energies but not at megavoltage energies. A small metastatic brain tumor in each of eight patients received 3-5-weekly fractions of 5 Gy equivalent per fraction from a CT scanner modified to deliver radiation therapy. In each patient, one additional tumor, lying completely outside the volume treated by CTRx, served as a control. The tumor receiving CTRx was treated after infusion of iodinated x-ray contrast media (CM) for dose enhancement. Many of these patients also received conventional 40 Gy whole brain radiation, before, during, or after CTRx treatment. None of the patients showed adverse reactions to the CM or necrosis of the normal brain from the CTRx boost radiation. Monte Carlo calculations of the radiation dose distributions in a model tumor showed that the CTRx irradiation of tumors carrying 10 mg or more of iodine per gram of tumor was as good or better than the dose distribution from conventional 10-MV X-rays. The treated tumor in two of the patients vanished after four treatments, whereas a control tumor in one patient remained constant and grew 4-fold in another patient. The CTRx concept effectively combines a modified CT scanner as a diagnostic device, as a simulator dedicated to radiotherapy, and as a treatment machine. Thus, CTRx could be very useful for radiation oncologists in controlling CM-enhanced and other small brain tumors.

  6. Studying frequency processing of the brain to enhance long-term memory and develop a human brain protocol.

    Science.gov (United States)

    Friedrich, Wernher; Du, Shengzhi; Balt, Karlien

    2015-01-01

    The temporal lobe in conjunction with the hippocampus is responsible for memory processing. The gamma wave is involved with this process. To develop a human brain protocol, a better understanding of the relationship between gamma and long-term memory is vital. A more comprehensive understanding of the human brain and specific analogue waves it uses will support the development of a human brain protocol. Fifty-eight participants aged between 6 and 60 years participated in long-term memory experiments. It is envisaged that the brain could be stimulated through binaural beats (sound frequency) at 40 Hz (gamma) to enhance long-term memory capacity. EEG recordings have been transformed to sound and then to an information standard, namely ASCII. Statistical analysis showed a proportional relationship between long-term memory and gamma activity. Results from EEG recordings indicate a pattern. The pattern was obtained through the de-codification of an EEG recording to sound and then to ASCII. Stimulation of gamma should enhance long term memory capacity. More research is required to unlock the human brains' protocol key. This key will enable the processing of information directly to and from human memory via gamma, the hippocampus and the temporal lobe.

  7. Precommissural Fornix in the Human Brain: A Diffusion Tensor Tractography Study

    OpenAIRE

    Yeo, Sang Seok; Seo, Jeong Pyo; Kwon, Yong Hyun; Jang, Sung Ho

    2013-01-01

    Purpose Other than a single case report, no diffusion tensor tractography (DTT) studies of the precommissural fornix in the human brain have been conducted. In the current study, we attempted to visualize the precommissural fornix in the human brain using DTT. Materials and Methods We recruited 36 healthy volunteers for this study. Diffusion tensor images were scanned using a 1.5-T scanner, and the precommissural fornix was analyzed using Functional Magnetic Resonance Imaging of the Brain (FM...

  8. The human sexual response cycle : Brain imaging evidence linking sex to other pleasures

    NARCIS (Netherlands)

    Georgiadis, J. R.; Kringelbach, M. L.

    Sexual behavior is critical to species survival, yet comparatively little is known about the neural mechanisms in the human brain. Here we systematically review the existing human brain imaging literature on sexual behavior and show that the functional neuroanatomy of sexual behavior is comparable

  9. Noninvasive quantification of human brain antioxidant concentrations after an intravenous bolus of vitamin C

    Science.gov (United States)

    Background: Until now, antioxidant based initiatives for preventing dementia have lacked a means to detect deficiency or measure pharmacologic effect in the human brain in situ. Objective: Our objective was to apply a novel method to measure key human brain antioxidant concentrations throughout the ...

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

    Science.gov (United States)

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

    2015-10-01

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

  11. Novel brain model for training of deep microvascular anastomosis.

    Science.gov (United States)

    Ishikawa, Tatsuya; Yasui, Nobuyuki; Ono, Hidenori

    2010-01-01

    Models of the brain and skull were developed using a selective laser sintering method for training in the procedures of deep microvascular anastomosis. Model A has an artificial skull with two craniotomies, providing fronto-temporal-subtemporal and suboccipital windows. The brain in Model A is soft and elastic, and consists of the brainstem and a hemispheric part with a detailed surface. Rehearsals or training for anastomosis to the insular part of the middle cerebral artery, superior cerebellar artery, posterior cerebral artery, and posterior inferior cerebellar artery can be performed through the craniotomies. Model B has an artificial skull with a bifrontal craniotomy and an artificial brain consisting of the bilateral frontal lobes with an interhemispheric fissure and corpus callosum. Rehearsals or training for anastomosis of the callosal segment of the anterior cerebral artery can be practiced through this craniotomy. These realistic models will help to develop skills for deep vascular anastomosis, which remains a challenging neurosurgical procedure, even for experienced neurosurgeons.

  12. Low resolution brain electromagnetic tomography in a realistic geometry head model: a simulation study

    International Nuclear Information System (INIS)

    Ding Lei; Lai Yuan; He Bin

    2005-01-01

    It is of importance to localize neural sources from scalp recorded EEG. Low resolution brain electromagnetic tomography (LORETA) has received considerable attention for localizing brain electrical sources. However, most such efforts have used spherical head models in representing the head volume conductor. Investigation of the performance of LORETA in a realistic geometry head model, as compared with the spherical model, will provide useful information guiding interpretation of data obtained by using the spherical head model. The performance of LORETA was evaluated by means of computer simulations. The boundary element method was used to solve the forward problem. A three-shell realistic geometry (RG) head model was constructed from MRI scans of a human subject. Dipole source configurations of a single dipole located at different regions of the brain with varying depth were used to assess the performance of LORETA in different regions of the brain. A three-sphere head model was also used to approximate the RG head model, and similar simulations performed, and results compared with the RG-LORETA with reference to the locations of the simulated sources. Multi-source localizations were discussed and examples given in the RG head model. Localization errors employing the spherical LORETA, with reference to the source locations within the realistic geometry head, were about 20-30 mm, for four brain regions evaluated: frontal, parietal, temporal and occipital regions. Localization errors employing the RG head model were about 10 mm over the same four brain regions. The present simulation results suggest that the use of the RG head model reduces the localization error of LORETA, and that the RG head model based LORETA is desirable if high localization accuracy is needed

  13. Exceptional evolutionary divergence of human muscle and brain metabolomes parallels human cognitive and physical uniqueness.

    Directory of Open Access Journals (Sweden)

    Katarzyna Bozek

    2014-05-01

    Full Text Available Metabolite concentrations reflect the physiological states of tissues and cells. However, the role of metabolic changes in species evolution is currently unknown. Here, we present a study of metabolome evolution conducted in three brain regions and two non-neural tissues from humans, chimpanzees, macaque monkeys, and mice based on over 10,000 hydrophilic compounds. While chimpanzee, macaque, and mouse metabolomes diverge following the genetic distances among species, we detect remarkable acceleration of metabolome evolution in human prefrontal cortex and skeletal muscle affecting neural and energy metabolism pathways. These metabolic changes could not be attributed to environmental conditions and were confirmed against the expression of their corresponding enzymes. We further conducted muscle strength tests in humans, chimpanzees, and macaques. The results suggest that, while humans are characterized by superior cognition, their muscular performance might be markedly inferior to that of chimpanzees and macaque monkeys.

  14. Mast Cell Infiltration in Human Brain Metastases Modulates the Microenvironment and Contributes to the Metastatic Potential

    Directory of Open Access Journals (Sweden)

    Ananya Roy

    2017-06-01

    Full Text Available Metastatic brain tumors continue to be a clinical problem, despite new therapeutic advances in cancer treatment. Brain metastases (BMs are among the most common mass lesions in the brain that are resistant to chemotherapies, have a very poor prognosis, and currently lack any efficient diagnostic tests. Predictions estimate that about 40% of lung and breast cancer patients will develop BM. Despite this, very little is known about the immunological and genetic aberrations that drive tumorigenesis in BM. In this study, we demonstrate the infiltration of mast cells (MCs in a large cohort of human BM samples with different tissues of origin for primary cancer. We applied patient-derived BM cell models to the study of BM cell–MC interactions. BM cells when cocultured with MCs demonstrate enhanced growth and self-renewal capacity. Gene set enrichment analyses indicate increased expression of signal transduction and transmembrane proteins related genes in the cocultured BM cells. MCs exert their effect by release of mediators such as IL-8, IL-10, matrix metalloprotease 2, and vascular endothelial growth factor, thereby permitting metastasis. In conclusion, we provide evidence for a role of MCs in BM. Our findings indicate MCs’ capability of modulating gene expression in BM cells and suggest that MCs can serve as a new target for drug development against metastases in the brain.

  15. Mathematical models of human behavior

    DEFF Research Database (Denmark)

    Møllgaard, Anders Edsberg

    During the last 15 years there has been an explosion in human behavioral data caused by the emergence of cheap electronics and online platforms. This has spawned a whole new research field called computational social science, which has a quantitative approach to the study of human behavior. Most...... studies have considered data sets with just one behavioral variable such as email communication. The Social Fabric interdisciplinary research project is an attempt to collect a more complete data set on human behavior by providing 1000 smartphones with pre-installed data collection software to students...... data set, along with work on other behavioral data. The overall goal is to contribute to a quantitative understanding of human behavior using big data and mathematical models. Central to the thesis is the determination of the predictability of different human activities. Upper limits are derived...

  16. The dynamic human brain : Genetic aspects in schizophrenia and health

    NARCIS (Netherlands)

    Brans, R.G.H.

    2009-01-01

    The general aim of this thesis is to explore the possible mechanisms underlying the individual differences in brain structure and brain structure change in healthy adults and schizophrenia patients. For this purpose, Magnetic Resonance Imaging scans of the brain were acquired in schizophrenia

  17. Default Mode Network, Motor Network, Dorsal and Ventral Basal Ganglia Networks in the Rat Brain: Comparison to Human Networks Using Resting State-fMRI

    Science.gov (United States)

    Sierakowiak, Adam; Monnot, Cyril; Aski, Sahar Nikkhou; Uppman, Martin; Li, Tie-Qiang; Damberg, Peter; Brené, Stefan

    2015-01-01

    Rodent models are developed to enhance understanding of the underlying biology of different brain disorders. However, before interpreting findings from animal models in a translational aspect to understand human disease, a fundamental step is to first have knowledge of similarities and differences of the biological systems studied. In this study, we analyzed and verified four known networks termed: default mode network, motor network, dorsal basal ganglia network, and ventral basal ganglia network using resting state functional MRI (rsfMRI) in humans and rats. Our work supports the notion that humans and rats have common robust resting state brain networks and that rsfMRI can be used as a translational tool when validating animal models of brain disorders. In the future, rsfMRI may be used, in addition to short-term interventions, to characterize longitudinal effects on functional brain networks after long-term intervention in humans and rats. PMID:25789862

  18. Expression and localization of claudins-3 and -12 in transformed human brain endothelium

    Directory of Open Access Journals (Sweden)

    Schrade Anja

    2012-02-01

    Full Text Available Abstract Background The aim of this study was to characterize the hCMEC/D3 cell line, an in vitro model of the human Blood Brain Barrier (BBB for the expression of brain endothelial specific claudins-3 and -12. Findings hCMEC/D3 cells express claudins-3 and -12. Claudin-3 is distinctly localized to the TJ whereas claudin -12 is observed in the perinuclear region and completely absent from TJs. We show that the expression of both proteins is lost in cell passage numbers where the BBB properties are no longer fully conserved. Expression and localization of claudin-3 is not modulated by simvastatin shown to improve barrier function in vitro and also recommended for routine hCMEC/D3 culture. Conclusions These results support conservation of claudin-3 and -12 expression in the hCMEC/D3 cell line and make claudin-3 a potential marker for BBB characteristics in vitro.

  19. The Increase of the Functional Entropy of the Human Brain with Age

    Science.gov (United States)

    Yao, Y.; Lu, W. L.; Xu, B.; Li, C. B.; Lin, C. P.; Waxman, D.; Feng, J. F.

    2013-01-01

    We use entropy to characterize intrinsic ageing properties of the human brain. Analysis of fMRI data from a large dataset of individuals, using resting state BOLD signals, demonstrated that a functional entropy associated with brain activity increases with age. During an average lifespan, the entropy, which was calculated from a population of individuals, increased by approximately 0.1 bits, due to correlations in BOLD activity becoming more widely distributed. We attribute this to the number of excitatory neurons and the excitatory conductance decreasing with age. Incorporating these properties into a computational model leads to quantitatively similar results to the fMRI data. Our dataset involved males and females and we found significant differences between them. The entropy of males at birth was lower than that of females. However, the entropies of the two sexes increase at different rates, and intersect at approximately 50 years; after this age, males have a larger entropy. PMID:24103922

  20. Walking through Architectural Spaces: The Impact of Interior Forms on Human Brain Dynamics

    Directory of Open Access Journals (Sweden)

    Maryam Banaei

    2017-09-01

    Full Text Available Neuroarchitecture uses neuroscientific tools to better understand architectural design and its impact on human perception and subjective experience. The form or shape of the built environment is fundamental to architectural design, but not many studies have shown the impact of different forms on the inhabitants’ emotions. This study investigated the neurophysiological correlates of different interior forms on the perceivers’ affective state and the accompanying brain activity. To understand the impact of naturalistic three-dimensional (3D architectural forms, it is essential to perceive forms from different perspectives. We computed clusters of form features extracted from pictures of residential interiors and constructed exemplary 3D room models based on and representing different formal clusters. To investigate human brain activity during 3D perception of architectural spaces, we used a mobile brain/body imaging (MoBI approach recording the electroencephalogram (EEG of participants while they naturally walk through different interior forms in virtual reality (VR. The results revealed a strong impact of curvature geometries on activity in the anterior cingulate cortex (ACC. Theta band activity in ACC correlated with specific feature types (rs (14 = 0.525, p = 0.037 and geometry (rs (14 = −0.579, p = 0.019, providing evidence for a role of this structure in processing architectural features beyond their emotional impact. The posterior cingulate cortex and the occipital lobe were involved in the perception of different room perspectives during the stroll through the rooms. This study sheds new light on the use of mobile EEG and VR in architectural studies and provides the opportunity to study human brain dynamics in participants that actively explore and realistically experience architectural spaces.

  1. Walking through Architectural Spaces: The Impact of Interior Forms on Human Brain Dynamics.

    Science.gov (United States)

    Banaei, Maryam; Hatami, Javad; Yazdanfar, Abbas; Gramann, Klaus

    2017-01-01

    Neuroarchitecture uses neuroscientific tools to better understand architectural design and its impact on human perception and subjective experience. The form or shape of the built environment is fundamental to architectural design, but not many studies have shown the impact of different forms on the inhabitants' emotions. This study investigated the neurophysiological correlates of different interior forms on the perceivers' affective state and the accompanying brain activity. To understand the impact of naturalistic three-dimensional (3D) architectural forms, it is essential to perceive forms from different perspectives. We computed clusters of form features extracted from pictures of residential interiors and constructed exemplary 3D room models based on and representing different formal clusters. To investigate human brain activity during 3D perception of architectural spaces, we used a mobile brain/body imaging (MoBI) approach recording the electroencephalogram (EEG) of participants while they naturally walk through different interior forms in virtual reality (VR). The results revealed a strong impact of curvature geometries on activity in the anterior cingulate cortex (ACC). Theta band activity in ACC correlated with specific feature types ( r s (14) = 0.525, p = 0.037) and geometry ( r s (14) = -0.579, p = 0.019), providing evidence for a role of this structure in processing architectural features beyond their emotional impact. The posterior cingulate cortex and the occipital lobe were involved in the perception of different room perspectives during the stroll through the rooms. This study sheds new light on the use of mobile EEG and VR in architectural studies and provides the opportunity to study human brain dynamics in participants that actively explore and realistically experience architectural spaces.

  2. Toxoplasma gondii-A Gastrointestinal Pathogen Associated with Human Brain Diseases.

    Science.gov (United States)

    Severance, E G; Xiao, J; Jones-Brando, L; Sabunciyan, S; Li, Y; Pletnikov, M; Prandovszky, E; Yolken, R

    2016-01-01

    Serious psychiatric disorders such as schizophrenia, bipolar disorder, and major depression are important causes of mortality and morbidity worldwide. While these are primarily diseases involving altered brain functioning, numerous studies have documented increased rates of gastrointestinal inflammation and dysfunction in many individuals with these disorders. Toxoplasma gondii is an apicomplexan protozoan intracellular parasite with a widespread distribution in both developed and developing countries. Toxoplasma organisms enter the ecosystem through the shedding of oocysts by Toxoplasma-infected felines. In almost all cases of postnatal human infection, Toxoplasma enters its hosts through the intestinal tract either by the ingestion of oocysts or by the consumption of meat from food animals which themselves were infected by Toxoplasma oocysts. It had previously been thought that most cases of Toxoplasma infection in immune competent children and adults were inapparent and asymptomatic. However, recent studies cast doubt on this concept as exposure to Toxoplasma has been associated with a range of acute and chronic symptoms. Of particular note has been the finding of an increased rate of a range of neurological and psychiatric disorders associated with serological evidence of Toxoplasma exposure. A role of Toxoplasma infection in brain diseases is also supported by the consistent finding of altered cognition and behavior in animal models of infections. Much of the attention relating to the role of Toxoplasma infection in neuropsychiatric disorders has focused on the brain, where Toxoplasma tissue cysts can persist for extended periods of time. However, recent discoveries relating to the role of the gastrointestinal tract in cognition and behavior suggest that Toxoplasma may also increase susceptibility to human brain diseases through immune activation, particularly involving the gastrointestinal mucosa. The study of the pathways relating to the pathobiology and

  3. Model brain based learning (BBL and whole brain teaching (WBT in learning

    Directory of Open Access Journals (Sweden)

    Baiq Sri Handayani

    2017-08-01

    Full Text Available The learning process is a process of change in behavior as a form of the result of learning. The learning model is a crucial component of the success of the learning process. The learning model is growing fastly, and each model has different characteristics. Teachers are required to be able to understand each model to teach the students optimally by matching the materials and the learning model. The best of the learning model is the model that based on the brain system in learning that are the model of Brain Based Learning (BBL and the model of Whole Brain Teaching (WBT. The purposes of this article are to