Science.gov

Sample records for brain integrating models

  1. The Virtual Brain Integrates Computational Modeling and Multimodal Neuroimaging

    PubMed Central

    Schirner, Michael; McIntosh, Anthony R.; Jirsa, Viktor K.

    2013-01-01

    Abstract Brain function is thought to emerge from the interactions among neuronal populations. Apart from traditional efforts to reproduce brain dynamics from the micro- to macroscopic scales, complementary approaches develop phenomenological models of lower complexity. Such macroscopic models typically generate only a few selected—ideally functionally relevant—aspects of the brain dynamics. Importantly, they often allow an understanding of the underlying mechanisms beyond computational reproduction. Adding detail to these models will widen their ability to reproduce a broader range of dynamic features of the brain. For instance, such models allow for the exploration of consequences of focal and distributed pathological changes in the system, enabling us to identify and develop approaches to counteract those unfavorable processes. Toward this end, The Virtual Brain (TVB) (www.thevirtualbrain.org), a neuroinformatics platform with a brain simulator that incorporates a range of neuronal models and dynamics at its core, has been developed. This integrated framework allows the model-based simulation, analysis, and inference of neurophysiological mechanisms over several brain scales that underlie the generation of macroscopic neuroimaging signals. In this article, we describe how TVB works, and we present the first proof of concept. PMID:23442172

  2. Efficient multilevel brain tumor segmentation with integrated bayesian model classification.

    PubMed

    Corso, J J; Sharon, E; Dube, S; El-Saden, S; Sinha, U; Yuille, A

    2008-05-01

    We present a new method for automatic segmentation of heterogeneous image data that takes a step toward bridging the gap between bottom-up affinity-based segmentation methods and top-down generative model based approaches. The main contribution of the paper is a Bayesian formulation for incorporating soft model assignments into the calculation of affinities, which are conventionally model free. We integrate the resulting model-aware affinities into the multilevel segmentation by weighted aggregation algorithm, and apply the technique to the task of detecting and segmenting brain tumor and edema in multichannel magnetic resonance (MR) volumes. The computationally efficient method runs orders of magnitude faster than current state-of-the-art techniques giving comparable or improved results. Our quantitative results indicate the benefit of incorporating model-aware affinities into the segmentation process for the difficult case of glioblastoma multiforme brain tumor.

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

    ERIC Educational Resources Information Center

    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…

  4. Multilevel segmentation and integrated bayesian model classification with an application to brain tumor segmentation.

    PubMed

    Corso, Jason J; Sharon, Eitan; Yuille, Alan

    2006-01-01

    We present a new method for automatic segmentation of heterogeneous image data, which is very common in medical image analysis. The main contribution of the paper is a mathematical formulation for incorporating soft model assignments into the calculation of affinities, which are traditionally model free. We integrate the resulting model-aware affinities into the multilevel segmentation by weighted aggregation algorithm. We apply the technique to the task of detecting and segmenting brain tumor and edema in multimodal MR volumes. Our results indicate the benefit of incorporating model-aware affinities into the segmentation process for the difficult case of brain tumor.

  5. Insights From an Integrated Physiologically Based Pharmacokinetic Model for Brain Penetration.

    PubMed

    Trapa, Patrick E; Belova, Elena; Liras, Jenny L; Scott, Dennis O; Steyn, Stefan J

    2016-02-01

    Central-nervous-system, physiologically based pharmacokinetic (PBPK) models predict exposure profiles in the brain, that is, the rate and extent of distribution. The current work develops one such model and presents improved methods for determining key input parameters. A simple linear regression statistical model estimates the passive permeability at the blood-brain barrier from brain uptake index data and descriptors, and a novel analysis extracts the relative active transport parameter from in vitro assays taking into consideration both paracellular transport and unstirred water layers. The integrated PBPK model captures the concentration profiles of both rate-restricted and effluxed compounds with high passive permeability. In many cases, compounds distribute rapidly into the brain and are, therefore, not rate limited. The PBPK model is then simplified to a straightforward equation to describe brain-to-plasma ratios at steady state. The equation can estimate brain penetration either from in vitro efflux data or from in vivo results from another species and, therefore, is a valuable tool in the discovery setting.

  6. Allostasis and the human brain: Integrating models of stress from the social and life sciences

    PubMed Central

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

    2009-01-01

    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 between stress and health, as well as the neural focus of “wear and tear” due to ongoing adaptation. This mediation, in turn, allows us to model the interplay over time between context, current stressor exposure, internal regulation of bodily processes, and health outcomes. We illustrate how this approach facilitates the integration of current findings in human neuroscience and genetics with key constructs from stress models from the social and life sciences, with implications for future research and the design of interventions targeting individuals at risk. PMID:20063966

  7. Integrated modeling of PET and DTI information based on conformal brain mapping

    NASA Astrophysics Data System (ADS)

    Zou, Guangyu; Xi, Yongjian; Heckenburg, Greg; Duan, Ye; Hua, Jing; Gu, Xiangfeng

    2006-03-01

    Recent advances in imaging technologies, such as Magnetic Resonance Imaging (MRI), Positron Emission Tomography (PET) and Diffusion Tensor Imaging (DTI) have accelerated brain research in many aspects. In order to better understand the synergy of the many processes involved in normal brain function, integrated modeling and analysis of MRI, PET, and DTI is highly desirable. Unfortunately, the current state-of-art computational tools fall short in offering a comprehensive computational framework that is accurate and mathematically rigorous. In this paper we present a framework which is based on conformal parameterization of a brain from high-resolution structural MRI data to a canonical spherical domain. This model allows natural integration of information from co-registered PET as well as DTI data and lays the foundation for a quantitative analysis of the relationship between diverse data sets. Consequently, the system can be designed to provide a software environment able to facilitate statistical detection of abnormal functional brain patterns in patients with a large number of neurological disorders.

  8. Modeling of Community Integration Trajectories in the First Five Years after Traumatic Brain Injury.

    PubMed

    Andelic, Nada; Arango-Lasprilla, Juan Carlos; Perrin, Paul B; Sigurdardottir, Solrun; Lu, Juan; Landa, Laiene Olabarrieta; Forslund, Marit V; Roe, Cecilie

    2016-01-01

    The aims of this study were to assess the trajectories of community integration in individuals with traumatic brain injury (TBI) through one, two, and five years post-injury and to examine whether those trajectories could be predicted by demographic and injury characteristics. A longitudinal cohort study was conducted with 105 individuals with moderate-to-severe TBI admitted to a trauma referral center in 2005-2007. Demographics and injury-related factors were extracted from medical records. At the one-, two- and five-year follow-ups, community integration was measured by the Community Integration Questionnaire (CIQ). A hierarchical linear model (HLM) examined whether longitudinal trajectories of community integration could be predicted by: time, sex, age, relationship status, education, employment status, occupation, acute Glasgow Coma Scale score, cause of injury, days in post-traumatic amnesia (PTA), computed tomography Marshall Score, and Injury Severity Score. CIQ scores improved across the three time-points (p<0.001). Additionally, higher trajectories of community integration were predicted by being single at the time of injury (p<.001), higher level of education (p=0.006), employment (p<0.001), and a shorter length of PTA (p<0.001). In a follow-up HLM with interaction terms, time*PTA was statistically significant (p<0.001), suggesting that participants with longer PTA increased in community integration more rapidly than those with shorter PTA. The longitudinal course of community integration described in this study may help rehabilitation professionals to plan more extensive follow-ups and targeted rehabilitation programs in the early stage of recovery for patients with specific demographic and injury characteristics.

  9. C5a alters blood-brain barrier integrity in a human in vitro model of systemic lupus erythematosus.

    PubMed

    Mahajan, Supriya D; Parikh, Neil U; Woodruff, Trent M; Jarvis, James N; Lopez, Molly; Hennon, Teresa; Cunningham, Patrick; Quigg, Richard J; Schwartz, Stanley A; Alexander, Jessy J

    2015-09-01

    The blood-brain barrier (BBB) plays a crucial role in brain homeostasis, thereby maintaining the brain environment precise for optimal neuronal function. Its dysfunction is an intriguing complication of systemic lupus erythematosus (SLE). SLE is a systemic autoimmune disorder where neurological complications occur in 5-50% of cases and is associated with impaired BBB integrity. Complement activation occurs in SLE and is an important part of the clinical profile. Our earlier studies demonstrated that C5a generated by complement activation caused the loss of brain endothelial layer integrity in rodents. The goal of the current study was to determine the translational potential of these studies to a human system. To assess this, we used a two dimensional in vitro BBB model constructed using primary human brain microvascular endothelial cells and astroglial cells, which closely emulates the in vivo BBB allowing the assessment of BBB integrity. Increased permeability monitored by changes in transendothelial electrical resistance and cytoskeletal remodelling caused by actin fiber rearrangement were observed when the cells were exposed to lupus serum and C5a, similar to the observations in mice. In addition, our data show that C5a/C5aR1 signalling alters nuclear factor-κB translocation into nucleus and regulates the expression of the tight junction proteins, claudin-5 and zonula occludens 1 in this setting. Our results demonstrate for the first time that C5a regulates BBB integrity in a neuroinflammatory setting where it affects both endothelial and astroglial cells. In addition, we also demonstrate that our previous findings in a mouse model, were emulated in human cells in vitro, bringing the studies one step closer to understanding the translational potential of C5a/C5aR1 blockade as a promising therapeutic strategy in SLE and other neurodegenerative diseases.

  10. Brain Functioning Models for Learning.

    ERIC Educational Resources Information Center

    Tipps, Steve; And Others

    This paper describes three models of brain function, each of which contributes to an integrated understanding of human learning. The first model, the up-and-down model, emphasizes the interconnection between brain structures and functions, and argues that since physiological, emotional, and cognitive responses are inseparable, the learning context…

  11. The "proactive" model of learning: Integrative framework for model-free and model-based reinforcement learning utilizing the associative learning-based proactive brain concept.

    PubMed

    Zsuga, Judit; Biro, Klara; Papp, Csaba; Tajti, Gabor; Gesztelyi, Rudolf

    2016-02-01

    Reinforcement learning (RL) is a powerful concept underlying forms of associative learning governed by the use of a scalar reward signal, with learning taking place if expectations are violated. RL may be assessed using model-based and model-free approaches. Model-based reinforcement learning involves the amygdala, the hippocampus, and the orbitofrontal cortex (OFC). The model-free system involves the pedunculopontine-tegmental nucleus (PPTgN), the ventral tegmental area (VTA) and the ventral striatum (VS). Based on the functional connectivity of VS, model-free and model based RL systems center on the VS that by integrating model-free signals (received as reward prediction error) and model-based reward related input computes value. Using the concept of reinforcement learning agent we propose that the VS serves as the value function component of the RL agent. Regarding the model utilized for model-based computations we turned to the proactive brain concept, which offers an ubiquitous function for the default network based on its great functional overlap with contextual associative areas. Hence, by means of the default network the brain continuously organizes its environment into context frames enabling the formulation of analogy-based association that are turned into predictions of what to expect. The OFC integrates reward-related information into context frames upon computing reward expectation by compiling stimulus-reward and context-reward information offered by the amygdala and hippocampus, respectively. Furthermore we suggest that the integration of model-based expectations regarding reward into the value signal is further supported by the efferent of the OFC that reach structures canonical for model-free learning (e.g., the PPTgN, VTA, and VS).

  12. Using Drosophila as an integrated model to study mild repetitive traumatic brain injury

    PubMed Central

    Barekat, Ayeh; Gonzalez, Arysa; Mauntz, Ruth E.; Kotzebue, Roxanne W.; Molina, Brandon; El-Mecharrafie, Nadja; Conner, Catherine J.; Garza, Shannon; Melkani, Girish C.; Joiner, William J.; Lipinski, Marta M.; Finley, Kim D.; Ratliff, Eric P.

    2016-01-01

    Traumatic brain injury (TBI) is a major cause of morbidity and mortality worldwide. In addition, there has been a growing appreciation that even repetitive, milder forms of TBI (mTBI) can have long-term deleterious consequences to neural tissues. Hampering our understanding of genetic and environmental factors that influence the cellular and molecular responses to injury has been the limited availability of effective genetic model systems that could be used to identify the key genes and pathways that modulate both the acute and long-term responses to TBI. Here we report the development of a severe and mild-repetitive TBI model using Drosophila. Using this system, key features that are typically found in mammalian TBI models were also identified in flies, including the activation of inflammatory and autophagy responses, increased Tau phosphorylation and neuronal defects that impair sleep-related behaviors. This novel injury paradigm demonstrates the utility of Drosophila as an effective tool to validate genetic and environmental factors that influence the whole animal response to trauma and to identify prospective therapies needed for the treatment of TBI. PMID:27143646

  13. Phenotypic Integration of Neurocranium and Brain

    PubMed Central

    RICHTSMEIER, JOAN T.; ALDRIDGE, KRISTINA; DeLEON, VALERIE B.; PANCHAL, JAYESH; KANE, ALEX A.; MARSH, JEFFREY L.; YAN, PENG; COLE, THEODORE M.

    2009-01-01

    Evolutionary history of Mammalia provides strong evidence that the morphology of skull and brain change jointly in evolution. Formation and development of brain and skull co-occur and are dependent upon a series of morphogenetic and patterning processes driven by genes and their regulatory programs. Our current concept of skull and brain as separate tissues results in distinct analyses of these tissues by most researchers. In this study, we use 3D computed tomography and magnetic resonance images of pediatric individuals diagnosed with premature closure of cranial sutures (craniosynostosis) to investigate phenotypic relationships between the brain and skull. It has been demonstrated previously that the skull and brain acquire characteristic dysmorphologies in isolated craniosynostosis, but relatively little is known of the developmental interactions that produce these anomalies. Our comparative analysis of phenotypic integration of brain and skull in premature closure of the sagittal and the right coronal sutures demonstrates that brain and skull are strongly integrated and that the significant differences in patterns of association do not occur local to the prematurely closed suture. We posit that the current focus on the suture as the basis for this condition may identify a proximate, but not the ultimate cause for these conditions. Given that premature suture closure reduces the number of cranial bones, and that a persistent loss of skull bones is demonstrated over the approximately 150 million years of synapsid evolution, craniosynostosis may serve as an informative model for evolution of the mammalian skull. PMID:16526048

  14. Modeling invariant object processing based on tight integration of simulated and empirical data in a Common Brain Space

    PubMed Central

    Peters, Judith C.; Reithler, Joel; Goebel, Rainer

    2012-01-01

    Recent advances in Computer Vision and Experimental Neuroscience provided insights into mechanisms underlying invariant object recognition. However, due to the different research aims in both fields models tended to evolve independently. A tighter integration between computational and empirical work may contribute to cross-fertilized development of (neurobiologically plausible) computational models and computationally defined empirical theories, which can be incrementally merged into a comprehensive brain model. After reviewing theoretical and empirical work on invariant object perception, this article proposes a novel framework in which neural network activity and measured neuroimaging data are interfaced in a common representational space. This enables direct quantitative comparisons between predicted and observed activity patterns within and across multiple stages of object processing, which may help to clarify how high-order invariant representations are created from low-level features. Given the advent of columnar-level imaging with high-resolution fMRI, it is time to capitalize on this new window into the brain and test which predictions of the various object recognition models are supported by this novel empirical evidence. PMID:22408617

  15. HITS-CLIP and integrative modeling define the Rbfox splicing-regulatory network linked to brain development and autism.

    PubMed

    Weyn-Vanhentenryck, Sebastien M; Mele, Aldo; Yan, Qinghong; Sun, Shuying; Farny, Natalie; Zhang, Zuo; Xue, Chenghai; Herre, Margaret; Silver, Pamela A; Zhang, Michael Q; Krainer, Adrian R; Darnell, Robert B; Zhang, Chaolin

    2014-03-27

    The RNA binding proteins Rbfox1/2/3 regulate alternative splicing in the nervous system, and disruption of Rbfox1 has been implicated in autism. However, comprehensive identification of functional Rbfox targets has been challenging. Here, we perform HITS-CLIP for all three Rbfox family members in order to globally map, at a single-nucleotide resolution, their in vivo RNA interaction sites in the mouse brain. We find that the two guanines in the Rbfox binding motif UGCAUG are critical for protein-RNA interactions and crosslinking. Using integrative modeling, these interaction sites, combined with additional datasets, define 1,059 direct Rbfox target alternative splicing events. Over half of the quantifiable targets show dynamic changes during brain development. Of particular interest are 111 events from 48 candidate autism-susceptibility genes, including syndromic autism genes Shank3, Cacna1c, and Tsc2. Alteration of Rbfox targets in some autistic brains is correlated with downregulation of all three Rbfox proteins, supporting the potential clinical relevance of the splicing-regulatory network.

  16. Superbinding in Integrative Brain Function and Memory

    DTIC Science & Technology

    2007-11-02

    A:\\basar.doc 1 SUPERBINDING IN INTEGRATIVE BRAIN FUNCTION AND MEMORY E. Basar1,2, M. Özgören1,2, S. Karakas1,3 1TUBITAK Brain Dynamics...percepts and integrative brain function. Keywords- superbinding, oscillations, binding, coherence 1 Aim of the report The present report aims to...introduce the superbinding theory to describe the machineries of integrative brain function instead of single neuron doctrine. This concept is based on

  17. Developing Enhanced Blood–Brain Barrier Permeability Models: Integrating External Bio-Assay Data in QSAR Modeling

    PubMed Central

    Wang, Wenyi; Kim, Marlene T.; Sedykh, Alexander

    2015-01-01

    Purpose Experimental Blood–Brain Barrier (BBB) permeability models for drug molecules are expensive and time-consuming. As alternative methods, several traditional Quantitative Structure-Activity Relationship (QSAR) models have been developed previously. In this study, we aimed to improve the predictivity of traditional QSAR BBB permeability models by employing relevant public bio-assay data in the modeling process. Methods We compiled a BBB permeability database consisting of 439 unique compounds from various resources. The database was split into a modeling set of 341 compounds and a validation set of 98 compounds. Consensus QSAR modeling workflow was employed on the modeling set to develop various QSAR models. A five-fold cross-validation approach was used to validate the developed models, and the resulting models were used to predict the external validation set compounds. Furthermore, we used previously published membrane transporter models to generate relevant transporter profiles for target compounds. The transporter profiles were used as additional biological descriptors to develop hybrid QSAR BBB models. Results The consensus QSAR models have R2=0.638 for fivefold cross-validation and R2=0.504 for external validation. The consensus model developed by pooling chemical and transporter descriptors showed better predictivity (R2=0.646 for five-fold cross-validation and R2=0.526 for external validation). Moreover, several external bio-assays that correlate with BBB permeability were identified using our automatic profiling tool. Conclusions The BBB permeability models developed in this study can be useful for early evaluation of new compounds (e.g., new drug candidates). The combination of chemical and biological descriptors shows a promising direction to improve the current traditional QSAR models. PMID:25862462

  18. Creating the brain and interacting with the brain: an integrated approach to understanding the brain.

    PubMed

    Morimoto, Jun; Kawato, Mitsuo

    2015-03-06

    In the past two decades, brain science and robotics have made gigantic advances in their own fields, and their interactions have generated several interdisciplinary research fields. First, in the 'understanding the brain by creating the brain' approach, computational neuroscience models have been applied to many robotics problems. Second, such brain-motivated fields as cognitive robotics and developmental robotics have emerged as interdisciplinary areas among robotics, neuroscience and cognitive science with special emphasis on humanoid robots. Third, in brain-machine interface research, a brain and a robot are mutually connected within a closed loop. In this paper, we review the theoretical backgrounds of these three interdisciplinary fields and their recent progress. Then, we introduce recent efforts to reintegrate these research fields into a coherent perspective and propose a new direction that integrates brain science and robotics where the decoding of information from the brain, robot control based on the decoded information and multimodal feedback to the brain from the robot are carried out in real time and in a closed loop.

  19. Identification of neuronal and angiogenic growth factors in an in vitro blood-brain barrier model system: Relevance in barrier integrity and tight junction formation and complexity.

    PubMed

    Freese, Christian; Hanada, Sanshiro; Fallier-Becker, Petra; Kirkpatrick, C James; Unger, Ronald E

    2017-05-01

    We previously demonstrated that the co-cultivation of endothelial cells with neural cells resulted in an improved integrity of the in vitro blood-brain barrier (BBB), and that this model could be useful to evaluate the transport properties of potential central nervous system disease drugs through the microvascular brain endothelial. In this study we have used real-time PCR, fluorescent microscopy, protein arrays and enzyme-linked immunosorbent assays to determine which neural- and endothelial cell-derived factors are produced in the co-culture and improve the integrity of the BBB. In addition, a further improvement of the BBB integrity was achieved by adjusting serum concentrations and growth factors or by the addition of brain pericytes. Under specific conditions expression of angiogenic, angiostatic and neurotrophic factors such as endostatin, pigment epithelium derived factor (PEDF/serpins-F1), tissue inhibitor of metalloproteinases (TIMP-1), and vascular endothelial cell growth factor (VEGF) closely mimicked the in vivo situation. Freeze-fracture analysis of these cultures demonstrated the quality and organization of the endothelial tight junction structures and their association to the two different lipidic leaflets of the membrane. Finally, a multi-cell culture model of the BBB with a transendothelial electrical resistance up to 371 (±15) Ω×cm(2) was developed, which may be useful for preliminary screening of drug transport across the BBB and to evaluate cellular crosstalk of cells involved in the neurovascular unit.

  20. Chronic rapamycin restores brain vascular integrity and function through NO synthase activation and improves memory in symptomatic mice modeling Alzheimer's disease

    PubMed Central

    Lin, Ai-Ling; Zheng, Wei; Halloran, Jonathan J; Burbank, Raquel R; Hussong, Stacy A; Hart, Matthew J; Javors, Martin; Shih, Yen-Yu Ian; Muir, Eric; Solano Fonseca, Rene; Strong, Randy; Richardson, Arlan G; Lechleiter, James D; Fox, Peter T; Galvan, Veronica

    2013-01-01

    Vascular pathology is a major feature of Alzheimer's disease (AD) and other dementias. We recently showed that chronic administration of the target-of-rapamycin (TOR) inhibitor rapamycin, which extends lifespan and delays aging, halts the progression of AD-like disease in transgenic human (h)APP mice modeling AD when administered before disease onset. Here we demonstrate that chronic reduction of TOR activity by rapamycin treatment started after disease onset restored cerebral blood flow (CBF) and brain vascular density, reduced cerebral amyloid angiopathy and microhemorrhages, decreased amyloid burden, and improved cognitive function in symptomatic hAPP (AD) mice. Like acetylcholine (ACh), a potent vasodilator, acute rapamycin treatment induced the phosphorylation of endothelial nitric oxide (NO) synthase (eNOS) and NO release in brain endothelium. Administration of the NOS inhibitor L-NG-Nitroarginine methyl ester reversed vasodilation as well as the protective effects of rapamycin on CBF and vasculature integrity, indicating that rapamycin preserves vascular density and CBF in AD mouse brains through NOS activation. Taken together, our data suggest that chronic reduction of TOR activity by rapamycin blocked the progression of AD-like cognitive and histopathological deficits by preserving brain vascular integrity and function. Drugs that inhibit the TOR pathway may have promise as a therapy for AD and possibly for vascular dementias. PMID:23801246

  1. The integration of large-scale neural network modeling and functional brain imaging in speech motor control

    PubMed Central

    Golfinopoulos, E.; Tourville, J.A.; Guenther, F.H.

    2009-01-01

    Speech production demands a number of integrated processing stages. The system must encode the speech motor programs that command movement trajectories of the articulators and monitor transient spatiotemporal variations in auditory and somatosensory feedback. Early models of this system proposed that independent neural regions perform specialized speech processes. As technology advanced, neuroimaging data revealed that the dynamic sensorimotor processes of speech require a distributed set of interacting neural regions. The DIVA (Directions into Velocities of Articulators) neurocomputational model elaborates on early theories, integrating existing data and contemporary ideologies, to provide a mechanistic account of acoustic, kinematic, and functional magnetic resonance imaging (fMRI) data on speech acquisition and production. This large-scale neural network model is composed of several interconnected components whose cell activities and synaptic weight strengths are governed by differential equations. Cells in the model are associated with neuroanatomical substrates and have been mapped to locations in Montreal Neurological Institute stereotactic space, providing a means to compare simulated and empirical fMRI data. The DIVA model also provides a computational and neurophysiological framework within which to interpret and organize research on speech acquisition and production in fluent and dysfluent child and adult speakers. The purpose of this review article is to demonstrate how the DIVA model is used to motivate and guide functional imaging studies. We describe how model predictions are evaluated using voxel-based, region-of-interest-based parametric analyses and inter-regional effective connectivity modeling of fMRI data. PMID:19837177

  2. A framework for integrating the songbird brain

    PubMed Central

    Smith, V.A.; Wada, K.; Rivas, M.V.; McElroy, M.; Smulders, T.V.; Carninci, P.; Hayashizaki, Y.; Dietrich, F.; Wu, X.; McConnell, P.; Yu, J.; Wang, P.P.; Hartemink, A.J.; Lin, S.

    2008-01-01

    Biological systems by default involve complex components with complex relationships. To decipher how biological systems work, we assume that one needs to integrate information over multiple levels of complexity. The songbird vocal communication system is ideal for such integration due to many years of ethological investigation and a discreet dedicated brain network. Here we announce the beginnings of a songbird brain integrative project that involves high-throughput, molecular, anatomical, electrophysiological and behavioral levels of analysis. We first formed a rationale for inclusion of specific biological levels of analysis, then developed high-throughput molecular technologies on songbird brains, developed technologies for combined analysis of electrophysiological activity and gene regulation in awake behaving animals, and developed bioinformatic tools that predict causal interactions within and between biological levels of organization. This integrative brain project is fitting for the interdisciplinary approaches taken in the current songbird issue of the Journal of Comparative Physiology A and is expected to be conducive to deciphering how brains generate and perceive complex behaviors. PMID:12471494

  3. Integrated Visualization of Human Brain Connectome Data.

    PubMed

    Li, Huang; Fang, Shiaofen; Goni, Joaquin; Contreras, Joey A; Liang, Yanhua; Cai, Chengtao; West, John D; Risacher, Shannon L; Wang, Yang; Sporns, Olaf; Saykin, Andrew J; Shen, Li

    2015-01-01

    Visualization plays a vital role in the analysis of multi-modal neuroimaging data. A major challenge in neuroimaging visualization is how to integrate structural, functional and connectivity data to form a comprehensive visual context for data exploration, quality control, and hypothesis discovery. We develop a new integrated visualization solution for brain imaging data by combining scientific and information visualization techniques within the context of the same anatomic structure. New surface texture techniques are developed to map non-spatial attributes onto the brain surfaces from MRI scans. Two types of non-spatial information are represented: (1) time-series data from resting-state functional MRI measuring brain activation; (2) network properties derived from structural connectivity data for different groups of subjects, which may help guide the detection of differentiation features. Through visual exploration, this integrated solution can help identify brain regions with highly correlated functional activations as well as their activation patterns. Visual detection of differentiation features can also potentially discover image based phenotypic biomarkers for brain diseases.

  4. Integrating Retinoic Acid Signaling with Brain Function

    ERIC Educational Resources Information Center

    Luo, Tuanlian; Wagner, Elisabeth; Drager, Ursula C.

    2009-01-01

    The vitamin A derivative retinoic acid (RA) regulates the transcription of about a 6th of the human genome. Compelling evidence indicates a role of RA in cognitive activities, but its integration with the molecular mechanisms of higher brain functions is not known. Here we describe the properties of RA signaling in the mouse, which point to…

  5. Brain Networks for Integrative Rhythm Formation

    PubMed Central

    Thaut, Michael H.; Demartin, Martina; Sanes, Jerome N.

    2008-01-01

    Background Performance of externally paced rhythmic movements requires brain and behavioral integration of sensory stimuli with motor commands. The underlying brain mechanisms to elaborate beat-synchronized rhythm and polyrhythms that musicians readily perform may differ. Given known roles in perceiving time and repetitive movements, we hypothesized that basal ganglia and cerebellar structures would have greater activation for polyrhythms than for on-the-beat rhythms. Methodology/Principal Findings Using functional MRI methods, we investigated brain networks for performing rhythmic movements paced by auditory cues. Musically trained participants performed rhythmic movements at 2 and 3 Hz either at a 1∶1 on-the-beat or with a 3∶2 or a 2∶3 stimulus-movement structure. Due to their prior musical experience, participants performed the 3∶2 or 2∶3 rhythmic movements automatically. Both the isorhythmic 1∶1 and the polyrhythmic 3∶2 or 2∶3 movements yielded the expected activation in contralateral primary motor cortex and related motor areas and ipsilateral cerebellum. Direct comparison of functional MRI signals obtained during 3∶2 or 2∶3 and on-the-beat rhythms indicated activation differences bilaterally in the supplementary motor area, ipsilaterally in the supramarginal gyrus and caudate-putamen and contralaterally in the cerebellum. Conclusions/Significance The activated brain areas suggest the existence of an interconnected brain network specific for complex sensory-motor rhythmic integration that might have specificity for elaboration of musical abilities. PMID:18509462

  6. Obesity, Fitness, and Brain Integrity in Adolescence

    PubMed Central

    Ross, Naima; Yau, Po Lai; Convit, Antonio

    2015-01-01

    Objective We set out to ascertain the relationship between insulin resistance, fitness, and brain structure and function in adolescents. Design and Methods We studied 79 obese and 51 non-obese participants who were recruited from the community, all without type 2 diabetes mellitus. All participants received medical, endocrine, neuropsychological, and MRI evaluations as well as a 6-minute walk test that was used to estimate fitness (maximal oxygen consumption). Results Obese adolescents had significantly thinner orbitofrontal cortices and performed significantly worse on Visual Working Memory tasks and the Digit Vigilance task. Insulin sensitivity and maximal oxygen consumption (VO2 max) were both highly correlated with central obesity and orbitofrontal cortical thickness, although insulin sensitivity was the stronger predictor for orbitofrontal cortical thickness. We also found that VO2 max was the only significant physiological variable related to visual working memory. Conclusions This is the first study to report positive associations between insulin resistance, VO2 max, and frontal lobe brain integrity in adolescents. Given the importance of brain health for learning and school performance, we conclude that schools should also emphasize physical fitness in order to maintain structural and functional brain integrity and facilitate academic achievement. PMID:25843937

  7. Genomic integrity and the ageing brain.

    PubMed

    Chow, Hei-man; Herrup, Karl

    2015-11-01

    DNA damage is correlated with and may drive the ageing process. Neurons in the brain are postmitotic and are excluded from many forms of DNA repair; therefore, neurons are vulnerable to various neurodegenerative diseases. The challenges facing the field are to understand how and when neuronal DNA damage accumulates, how this loss of genomic integrity might serve as a 'time keeper' of nerve cell ageing and why this process manifests itself as different diseases in different individuals.

  8. Consciousness, information integration, and the brain.

    PubMed

    Tononi, Giulio

    2005-01-01

    Clinical observations have established that certain parts of the brain are essential for consciousness whereas other parts are not. For example, different areas of the cerebral cortex contribute different modalities and submodalities of consciousness, whereas the cerebellum does not, despite having even more neurons. It is also well established that consciousness depends on the way the brain functions. For example, consciousness is much reduced during slow wave sleep and generalized seizures, even though the levels of neural activity are comparable or higher than in wakefulness. To understand why this is so, empirical observations on the neural correlates of consciousness need to be complemented by a principled theoretical approach. Otherwise, it is unlikely that we could ever establish to what extent consciousness is present in neurological conditions such as akinetic mutism, psychomotor seizures, or sleepwalking, and to what extent it is present in newborn babies and animals. A principled approach is provided by the information integration theory of consciousness. This theory claims that consciousness corresponds to a system's capacity to integrate information, and proposes a way to measure such capacity. The information integration theory can account for several neurobiological observations concerning consciousness, including: (i) the association of consciousness with certain neural systems rather than with others; (ii) the fact that neural processes underlying consciousness can influence or be influenced by neural processes that remain unconscious; (iii) the reduction of consciousness during dreamless sleep and generalized seizures; and (iv) the time requirements on neural interactions that support consciousness.

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

    PubMed Central

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

    2015-01-01

    Network-based analyses of brain imaging data consistently reveal distinct modules and connector nodes with diverse global connectivity across the modules. How discrete the functions of modules are, how dependent the computational load of each module is to the other modules’ processing, and what the precise role of connector nodes is for between-module communication remains underspecified. Here, we use a network model of the brain derived from resting-state functional MRI (rs-fMRI) data and investigate the modular functional architecture of the human brain by analyzing activity at different types of nodes in the network across 9,208 experiments of 77 cognitive tasks in the BrainMap database. Using an author–topic model of cognitive functions, we find a strong spatial correspondence between the cognitive functions and the network’s modules, suggesting that each module performs a discrete cognitive function. Crucially, activity at local nodes within the modules does not increase in tasks that require more cognitive functions, demonstrating the autonomy of modules’ functions. However, connector nodes do exhibit increased activity when more cognitive functions are engaged in a task. Moreover, connector nodes are located where brain activity is associated with many different cognitive functions. Connector nodes potentially play a role in between-module communication that maintains the modular function of the brain. Together, these findings provide a network account of the brain’s modular yet integrated implementation of cognitive functions. PMID:26598686

  10. Functional Anatomy of the Thalamus as a Model of Integrated Structural and Functional Connectivity of the Human Brain In Vivo.

    PubMed

    Mastropasqua, Chiara; Bozzali, Marco; Spanò, Barbara; Koch, Giacomo; Cercignani, Mara

    2015-07-01

    While methods of measuring non-invasively both, functional and structural brain connectivity are available, the degree of overlap between them is still unknown. In this paper this issue is addressed by investigating the connectivity pattern of a brain structure with many, well characterized structural connections, namely the thalamus. Diffusion-weighted and resting state (RS) functional MRI (fMRI) data were collected in a group of 38 healthy participants. Probabilistic tractography was performed to parcellate the thalamus into regions structurally connected to different cortical areas. The resulting regions were used as seeds for seed-based analysis of RS fMRI data. The tractographic parcellation was thus cross-validated against functional connectivity data by evaluating the overlap between the functional and structural thalamo-cortical connections originating from the parcellated regions. Our data show only a partial overall correspondence between structural and functional connections, in the same group of healthy individuals, thus suggesting that the two approaches provide complementary and not overlapping information. Future studies are warranted to extend the results we obtained in the thalamus to other structures, and to confirm that the mechanisms behind functional connectivity are more complex than just expressing structural connectivity.

  11. Integrated Modeling Systems

    DTIC Science & Technology

    1989-01-01

    Summer 1979). WMSI Working Paper No. 291A. 173 Dyer , J. and R. Sarin. "Measurable Multiattribute Value Functions," Operations Research. 27:4 (July...J. McCall. "Expected Utility Maximizing Job Search," Chapter 7 of Studies in the Economics of Search, 1979, North-Holland. WMSI Working Paper No. 274...model integration, solver integration, and integration of various utilities . Model integration is further divided into four subtypes based on a four-level

  12. A Right Brain/Left Brain Model of Acting.

    ERIC Educational Resources Information Center

    Bowlen, Clark

    Using current right brain/left brain research, this paper develops a model that explains acting's underlying quality--the actor is both himself and the character. Part 1 presents (1) the background of the right brain/left brain theory, (2) studies showing that propositional communication is a left hemisphere function while affective communication…

  13. The Integrated Medical Model

    NASA Technical Reports Server (NTRS)

    Kerstman, Eric; Minard, Charles; Saile, Lynn; Freiere deCarvalho, Mary; Myers, Jerry; Walton, Marlei; Butler, Douglas; Iyengar, Sriram; Johnson-Throop, Kathy; Baumann, David

    2010-01-01

    The goals of the Integrated Medical Model (IMM) are to develop an integrated, quantified, evidence-based decision support tool useful to crew health and mission planners and to help align science, technology, and operational activities intended to optimize crew health, safety, and mission success. Presentation slides address scope and approach, beneficiaries of IMM capabilities, history, risk components, conceptual models, development steps, and the evidence base. Space adaptation syndrome is used to demonstrate the model's capabilities.

  14. Integrating neuroinformatics tools in TheVirtualBrain

    PubMed Central

    Woodman, M. Marmaduke; Pezard, Laurent; Domide, Lia; Knock, Stuart A.; Sanz-Leon, Paula; Mersmann, Jochen; McIntosh, Anthony R.; Jirsa, Viktor

    2014-01-01

    TheVirtualBrain (TVB) is a neuroinformatics Python package representing the convergence of clinical, systems, and theoretical neuroscience in the analysis, visualization and modeling of neural and neuroimaging dynamics. TVB is composed of a flexible simulator for neural dynamics measured across scales from local populations to large-scale dynamics measured by electroencephalography (EEG), magnetoencephalography (MEG) and functional magnetic resonance imaging (fMRI), and core analytic and visualization functions, all accessible through a web browser user interface. A datatype system modeling neuroscientific data ties together these pieces with persistent data storage, based on a combination of SQL and HDF5. These datatypes combine with adapters allowing TVB to integrate other algorithms or computational systems. TVB provides infrastructure for multiple projects and multiple users, possibly participating under multiple roles. For example, a clinician might import patient data to identify several potential lesion points in the patient's connectome. A modeler, working on the same project, tests these points for viability through whole brain simulation, based on the patient's connectome, and subsequent analysis of dynamical features. TVB also drives research forward: the simulator itself represents the culmination of several simulation frameworks in the modeling literature. The availability of the numerical methods, set of neural mass models and forward solutions allows for the construction of a wide range of brain-scale simulation scenarios. This paper briefly outlines the history and motivation for TVB, describing the framework and simulator, giving usage examples in the web UI and Python scripting. PMID:24795617

  15. Integrated Modeling Environment

    NASA Technical Reports Server (NTRS)

    Mosier, Gary; Stone, Paul; Holtery, Christopher

    2006-01-01

    The Integrated Modeling Environment (IME) is a software system that establishes a centralized Web-based interface for integrating people (who may be geographically dispersed), processes, and data involved in a common engineering project. The IME includes software tools for life-cycle management, configuration management, visualization, and collaboration.

  16. Structural model integrity

    NASA Technical Reports Server (NTRS)

    Wallerstein, D. V.; Lahey, R. S.; Haggenmacher, G. W.

    1977-01-01

    Many of the practical aspects and problems of ensuring the integrity of a structural model are discussed, as well as the steps which have been taken in the NASTRAN system to assure that these checks can be routinely performed. Model integrity as used applies not only to the structural model but also to the loads applied to the model. Emphasis is also placed on the fact that when dealing with substructure analysis, all of the checking procedures discussed should be applied at the lowest level of substructure prior to any coupling.

  17. Brain temperature changes during selective cooling with endovascular intracarotid cold saline infusion: simulation using human data fitted with an integrated mathematical model.

    PubMed

    Neimark, Matthew Aaron Harold; Konstas, Angelos Aristeidis; Lee, Leslie; Laine, Andrew Francis; Pile-Spellman, John; Choi, Jae

    2013-03-01

    The feasibility of rapid cerebral hypothermia induction in humans with intracarotid cold saline infusion (ICSI) was investigated using a hybrid approach of jugular venous bulb temperature (JVBT) sampling and mathematical modeling of transient and steady state brain temperature distribution. This study utilized both forward mathematical modeling, in which brain temperatures were predicted based on input saline temperatures, and inverse modeling, where brain temperatures were inferred based on JVBT. Changes in ipsilateral anterior circulation territory temperature (IACT) were estimated in eight patients as a result of 10 min of a cold saline infusion of 33 ml/min. During ICSI, the measured JVBT dropped by 0.76±0.18°C while the modeled JVBT decreased by 0.86±0.18°C. The modeled IACT decreased by 2.1±0.23°C. In the inverse model, IACT decreased by 1.9±0.23°C. The results of this study suggest that mild cerebral hypothermia can be induced rapidly and safely with ICSI in the neuroangiographical setting. The JVBT corrected mathematical model can be used as a non-invasive estimate of transient and steady state cerebral temperature changes.

  18. Cyberinfrastructure for the digital brain: spatial standards for integrating rodent brain atlases

    PubMed Central

    Zaslavsky, Ilya; Baldock, Richard A.; Boline, Jyl

    2014-01-01

    Biomedical research entails capture and analysis of massive data volumes and new discoveries arise from data-integration and mining. This is only possible if data can be mapped onto a common framework such as the genome for genomic data. In neuroscience, the framework is intrinsically spatial and based on a number of paper atlases. This cannot meet today's data-intensive analysis and integration challenges. A scalable and extensible software infrastructure that is standards based but open for novel data and resources, is required for integrating information such as signal distributions, gene-expression, neuronal connectivity, electrophysiology, anatomy, and developmental processes. Therefore, the International Neuroinformatics Coordinating Facility (INCF) initiated the development of a spatial framework for neuroscience data integration with an associated Digital Atlasing Infrastructure (DAI). A prototype implementation of this infrastructure for the rodent brain is reported here. The infrastructure is based on a collection of reference spaces to which data is mapped at the required resolution, such as the Waxholm Space (WHS), a 3D reconstruction of the brain generated using high-resolution, multi-channel microMRI. The core standards of the digital atlasing service-oriented infrastructure include Waxholm Markup Language (WaxML): XML schema expressing a uniform information model for key elements such as coordinate systems, transformations, points of interest (POI)s, labels, and annotations; and Atlas Web Services: interfaces for querying and updating atlas data. The services return WaxML-encoded documents with information about capabilities, spatial reference systems (SRSs) and structures, and execute coordinate transformations and POI-based requests. Key elements of INCF-DAI cyberinfrastructure have been prototyped for both mouse and rat brain atlas sources, including the Allen Mouse Brain Atlas, UCSD Cell-Centered Database, and Edinburgh Mouse Atlas Project. PMID

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

    PubMed

    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.

  20. Searching for the one and many emotional brains. Comment on "The quartet theory of human emotions: An integrative and neurofunctional model" by S. Koelsch et al.

    NASA Astrophysics Data System (ADS)

    Armony, Jorge L.

    2015-06-01

    Over the past hundred years or so, several neurally-based, or at least neurally-inspired, models of emotion have been proposed, with varying degrees of acceptance and success. Early ones were mostly based on data obtained from experiments conducted in non-human animals using classical conditioning paradigms, thus focusing on defensive (threat) and appetitive (reward) behaviors. Some features of the models were sometimes confirmed as being also applicable to humans, usually in experiments with patients suffering from focal brain lesions - although inconsistent, or even contradictory findings were often reported.

  1. The Integrated Medical Model

    NASA Technical Reports Server (NTRS)

    Butler, Douglas J.; Kerstman, Eric

    2010-01-01

    This slide presentation reviews the goals and approach for the Integrated Medical Model (IMM). The IMM is a software decision support tool that forecasts medical events during spaceflight and optimizes medical systems during simulations. It includes information on the software capabilities, program stakeholders, use history, and the software logic.

  2. An Integrated Model Recontextualized

    ERIC Educational Resources Information Center

    O'Meara, KerryAnn; Saltmarsh, John

    2016-01-01

    In this commentary, authors KerryAnn O'Meara and John Saltmarsh reflect on their 2008 "Journal of Higher Education Outreach and Engagement" article "An Integrated Model for Advancing the Scholarship of Engagement: Creating Academic Homes for the Engaged Scholar," reprinted in this 20th anniversary issue of "Journal of…

  3. Dynamic Functional Segregation and Integration in Human Brain Network During Complex Tasks.

    PubMed

    Ren, Shen; Li, Junhua; Taya, Fumihiko; deSouza, Joshua; Thakor, Nitish; Bezerianos, Anastasios

    2016-09-09

    The analysis of the topology and organisation of brain networks is known to greatly benefit from network measures in graph theory. However, to evaluate dynamic changes of brain functional connectivity, more sophisticated quantitative metrics characterising temporal evolution of brain topological features are required. To simplify conversion of time-varying brain connectivity to a static graph representation is straightforward but the procedure loses temporal information that could be critical in understanding the brain functions. To extend the understandings of functional segregation and integration to a dynamic fashion, we recommend dynamic graph metrics to characterise temporal changes of topological features of brain networks. This study investigated functional segregation and integration of brain networks over time by dynamic graph metrics derived from EEG signals during an experimental protocol: performance of complex flight simulation tasks with multiple levels of difficulty. We modelled time-varying brain functional connectivity as multilayer networks, in which each layer models brain connectivity at time window t + t. Dynamic graph metrics were calculated to quantify temporal and topological properties of the network. Results show that brain networks under the performance of complex tasks reveal a dynamic small-world architecture with a number of frequently connected nodes or hubs, which supports the balance of information segregation and integration in brain over time. The results also show that greater cognitive workloads caused by more difficult tasks induced a more globally efficient but less clustered dynamic small-world functional network. Our study illustrates that task-related changes of functional brain network segregation and integration can be characterised by dynamic graph metrics.

  4. Hierarchical Models in the Brain

    PubMed Central

    Friston, Karl

    2008-01-01

    This paper describes a general model that subsumes many parametric models for continuous data. The model comprises hidden layers of state-space or dynamic causal models, arranged so that the output of one provides input to another. The ensuing hierarchy furnishes a model for many types of data, of arbitrary complexity. Special cases range from the general linear model for static data to generalised convolution models, with system noise, for nonlinear time-series analysis. Crucially, all of these models can be inverted using exactly the same scheme, namely, dynamic expectation maximization. This means that a single model and optimisation scheme can be used to invert a wide range of models. We present the model and a brief review of its inversion to disclose the relationships among, apparently, diverse generative models of empirical data. We then show that this inversion can be formulated as a simple neural network and may provide a useful metaphor for inference and learning in the brain. PMID:18989391

  5. What Brain Sciences Reveal about Integrating Theory and Practice

    ERIC Educational Resources Information Center

    Patton, Michael Quinn

    2014-01-01

    Theory and practice are integrated in the human brain. Situation recognition and response are key to this integration. Scholars of decision making and expertise have found that people with great expertise are more adept at situational recognition and intentional about their decision-making processes. Several interdisciplinary fields of inquiry…

  6. Epigenetic Integration of the Developing Brain and Face

    PubMed Central

    Parsons, Trish E.; Schmidt, Eric J.; Boughner, Julia C.; Jamniczky, Heather A.; Marcucio, Ralph S.; Hallgrímsson, Benedikt

    2011-01-01

    The integration of the brain and face and to what extent this relationship constrains or enables evolutionary change in the craniofacial complex is an issue of long-standing interest in vertebrate evolution. To investigate brain-face integration, we studied the covariation between the forebrain and midface at gestational days 10-10.5 in four strains of laboratory mice. We found that phenotypic variation in the forebrain is highly correlated with that of the face during face formation such that variation in the size of the forebrain correlates with the degree of prognathism and orientation of the facial prominences. This suggests strongly that the integration of the brain and face is relevant to the etiology of midfacial malformations such as orofacial clefts. This axis of integration also has important implications for the evolutionary developmental biology of the mammalian craniofacial complex. PMID:21901785

  7. Left Brain, Right Brain, Super Brain: The Holistic Model.

    ERIC Educational Resources Information Center

    Yellin, David

    Recent discoveries about the whole brain seem to call for a holistic approach to learning, one in which educators would teach the whole person, including physical and emotional states as well as cognitive abilities. Three holistic techniques are particularly relevant to education: (1) biofeedback; (2) yoga; and (3) the Lozanov method. Biofeedback…

  8. Cognitive Models as Bridge between Brain and Behavior.

    PubMed

    Love, Bradley C

    2016-04-01

    How can disparate neural and behavioral measures be integrated? Turner and colleagues propose joint modeling as a solution. Joint modeling mutually constrains the interpretation of brain and behavioral measures by exploiting their covariation structure. Simultaneous estimation allows for more accurate prediction than would be possible by considering these measures in isolation.

  9. Integrated Assessment Modeling

    SciTech Connect

    Edmonds, James A.; Calvin, Katherine V.; Clarke, Leon E.; Janetos, Anthony C.; Kim, Son H.; Wise, Marshall A.; McJeon, Haewon C.

    2012-10-31

    This paper discusses the role of Integrated Assessment models (IAMs) in climate change research. IAMs are an interdisciplinary research platform, which constitutes a consistent scientific framework in which the large-scale interactions between human and natural Earth systems can be examined. In so doing, IAMs provide insights that would otherwise be unavailable from traditional single-discipline research. By providing a broader view of the issue, IAMs constitute an important tool for decision support. IAMs are also a home of human Earth system research and provide natural Earth system scientists information about the nature of human intervention in global biogeophysical and geochemical processes.

  10. Cardiorespiratory fitness and brain volume and white matter integrity

    PubMed Central

    Zhu, Na; Schreiner, Pamela J.; Launer, Lenore J.; Whitmer, Rachel A.; Sidney, Stephen; Demerath, Ellen; Thomas, William; Bouchard, Claude; He, Ka; Erus, Guray; Battapady, Harsha; Bryan, R. Nick

    2015-01-01

    Objective: We hypothesized that greater cardiorespiratory fitness is associated with lower odds of having unfavorable brain MRI findings. Methods: We studied 565 healthy, middle-aged, black and white men and women in the CARDIA (Coronary Artery Risk Development in Young Adults) Study. The fitness measure was symptom-limited maximal treadmill test duration (Maxdur); brain MRI was measured 5 years later. Brain MRI measures were analyzed as means and as proportions below the 15th percentile (above the 85th percentile for white matter abnormal tissue volume). Results: Per 1-minute-higher Maxdur, the odds ratio for having less whole brain volume was 0.85 (p = 0.04) and for having low white matter integrity was 0.80 (p = 0.02), adjusted for age, race, sex, clinic, body mass index, smoking, alcohol, diet, physical activity, education, blood pressure, diabetes, total cholesterol, and lung function (plus intracranial volume for white matter integrity). No significant associations were observed between Maxdur and abnormal tissue volume or blood flow in white matter. Findings were similar for associations with continuous brain MRI measures. Conclusions: Greater physical fitness was associated with more brain volume and greater white matter integrity measured 5 years later in middle-aged adults. PMID:25957331

  11. Extensive abnormality of brain white matter integrity in pathological gambling.

    PubMed

    Joutsa, Juho; Saunavaara, Jani; Parkkola, Riitta; Niemelä, Solja; Kaasinen, Valtteri

    2011-12-30

    Several magnetic resonance imaging (MRI) studies in substance use disorders have shown brain white matter integrity abnormalities, but there are no studies in pathological gambling, a form of behavioral addiction. Our objective was to investigate possible changes in regional brain gray and white matter volumes, and axonal white matter integrity in pathological gamblers compared to healthy controls. Twenty-four subjects (12 clinically diagnosed male pathological gamblers and 12 age-matched healthy male volunteers) underwent structural and diffusion weighted brain MRI scans, which were analyzed with voxel-based morphometry and tract based spatial statistics. In pathological gamblers, widespread lower white matter integrity (lower fractional anisotropy, higher mean diffusivity) was seen in multiple brain regions including the corpus callosum, the cingulum, the superior longitudinal fascicle, the inferior fronto-occipital fascicle, the anterior limb of internal capsule, the anterior thalamic radiation, the inferior longitudinal fascicle and the uncinate/inferior fronto-occipital fascicle. There were no volumetric differences in gray or white matter between pathological gamblers and controls. The results suggest that pathological gambling is associated with extensive lower integrity of several brain white matter tracts. The diffusion abnormality closely resembles previous findings in individuals with substance addictions.

  12. Mixed oligomers and monomeric amyloid-β disrupts endothelial cells integrity and reduces monomeric amyloid-β transport across hCMEC/D3 cell line as an in vitro blood-brain barrier model.

    PubMed

    Qosa, Hisham; LeVine, Harry; Keller, Jeffrey N; Kaddoumi, Amal

    2014-09-01

    Senile amyloid plaques are one of the diagnostic hallmarks of Alzheimer's disease (AD). However, the severity of clinical symptoms of AD is weakly correlated with the plaque load. AD symptoms severity is reported to be more strongly correlated with the level of soluble amyloid-β (Aβ) assemblies. Formation of soluble Aβ assemblies is stimulated by monomeric Aβ accumulation in the brain, which has been related to its faulty cerebral clearance. Studies tend to focus on the neurotoxicity of specific Aβ species. There are relatively few studies investigating toxic effects of Aβ on the endothelial cells of the blood-brain barrier (BBB). We hypothesized that a soluble Aβ pool more closely resembling the in vivo situation composed of a mixture of Aβ40 monomer and Aβ42 oligomer would exert higher toxicity against hCMEC/D3 cells as an in vitro BBB model than either component alone. We observed that, in addition to a disruptive effect on the endothelial cells integrity due to enhancement of the paracellular permeability of the hCMEC/D3 monolayer, the Aβ mixture significantly decreased monomeric Aβ transport across the cell culture model. Consistent with its effect on Aβ transport, Aβ mixture treatment for 24h resulted in LRP1 down-regulation and RAGE up-regulation in hCMEC/D3 cells. The individual Aβ species separately failed to alter Aβ clearance or the cell-based BBB model integrity. Our study offers, for the first time, evidence that a mixture of soluble Aβ species, at nanomolar concentrations, disrupts endothelial cells integrity and its own transport across an in vitro model of the BBB.

  13. Glacial integrative modelling.

    PubMed

    Ganopolski, Andrey

    2003-09-15

    Understanding the mechanisms of past climate changes requires modelling of the complex interaction between all major components of the Earth system: atmosphere, ocean, cryosphere, lithosphere and biosphere. This paper reviews attempts at such an integrative approach to modelling climate changes during the glacial age. In particular, the roles of different factors in shaping glacial climate are compared based on the results of simulations with an Earth-system model of intermediate complexity, CLIMBER-2. It is shown that ice sheets, changes in atmospheric compositions, vegetation cover, and reorganization of the ocean thermohaline circulation play important roles in glacial climate changes. Another example of this approach is the modelling of two major types of abrupt glacial climate changes: Dansgaard-Oeschger and Heinrich events. Our results corroborate some of the early proposed mechanisms, which relate abrupt climate changes to the internal instability of the ocean thermohaline circulation and ice sheets. At the same time, it is shown that realistic representation of the temporal evolution of the palaeoclimatic background is crucial to simulate observed features of the glacial abrupt climate changes.

  14. The organization of prefrontal-subthalamic inputs in primates provides an anatomical substrate for both functional specificity and integration: implications for basal ganglia models and deep brain stimulation

    PubMed Central

    Haynes, William I. A.; Haber, Suzanne N.

    2013-01-01

    The identification of a hyperdirect cortico-subthalamic nucleus connection highlighted the important role of the subthalamic nucleus (STN) in regulating behavior. However, this pathway was shown primarily from motor areas. Hyperdirect pathways associated with cognitive and motivational cortical regions are particularly relevant given recent data from deep brain stimulation, both for neurological and psychiatric disorders. Our experiments were designed to: demonstrate the existence and organization of prefrontal-STN projections, help delineate the ‘limbic’ STN, and determine whether convergence between cortico-STN fibers from functionally diverse cortical areas exists in the STN. We injected anterograde tracers in the ventromedial prefrontal, orbitofrontal, anterior cingulate and dorsal prefrontal cortices of Macaca nemestrina & M. fascicularis to analyze the organization of terminals and passing fibers in the STN. Results show a topographically organized prefrontal hyperdirect pathway in primates. Limbic areas project to the medial tip of the nucleus, straddling its border and extending into the lateral hypothalamus. Associative areas project to the medial half, motor areas to the lateral half. Limbic projections terminated primarily rostrally and motor projections more caudally. The extension of limbic projections into the lateral hypothalamus, suggests that this region be included in the STN. A high degree of convergence exists between projections from functionally diverse cortical areas, creating potentially important interfaces between terminal fields. Taken together, the results provide an anatomical substrate to extend the role of the hyperdirect pathway in models of basal ganglia function, and new keys for understanding deep brain stimulation effects on cognitive and motivational aspects of behavior. PMID:23486951

  15. Integrated Medical Model Overview

    NASA Technical Reports Server (NTRS)

    Myers, J.; Boley, L.; Foy, M.; Goodenow, D.; Griffin, D.; Keenan, A.; Kerstman, E.; Melton, S.; McGuire, K.; Saile, L.; Shah, R.; Garcia, Y.; Sirmons. B.; Walton, M.; Reyes, D.

    2015-01-01

    The Integrated Medical Model (IMM) Project represents one aspect of NASA's Human Research Program (HRP) to quantitatively assess medical risks to astronauts for existing operational missions as well as missions associated with future exploration and commercial space flight ventures. The IMM takes a probabilistic approach to assessing the likelihood and specific outcomes of one hundred medical conditions within the envelope of accepted space flight standards of care over a selectable range of mission capabilities. A specially developed Integrated Medical Evidence Database (iMED) maintains evidence-based, organizational knowledge across a variety of data sources. Since becoming operational in 2011, version 3.0 of the IMM, the supporting iMED, and the expertise of the IMM project team have contributed to a wide range of decision and informational processes for the space medical and human research community. This presentation provides an overview of the IMM conceptual architecture and range of application through examples of actual space flight community questions posed to the IMM project.

  16. Brain white matter tract integrity as a neural foundation for general intelligence.

    PubMed

    Penke, L; Maniega, S Muñoz; Bastin, M E; Valdés Hernández, M C; Murray, C; Royle, N A; Starr, J M; Wardlaw, J M; Deary, I J

    2012-10-01

    General intelligence is a robust predictor of important life outcomes, including educational and occupational attainment, successfully managing everyday life situations, good health and longevity. Some neuronal correlates of intelligence have been discovered, mainly indicating that larger cortices in widespread parieto-frontal brain networks and efficient neuronal information processing support higher intelligence. However, there is a lack of established associations between general intelligence and any basic structural brain parameters that have a clear functional meaning. Here, we provide evidence that lower brain-wide white matter tract integrity exerts a substantial negative effect on general intelligence through reduced information-processing speed. Structural brain magnetic resonance imaging scans were acquired from 420 older adults in their early 70s. Using quantitative tractography, we measured fractional anisotropy and two white matter integrity biomarkers that are novel to the study of intelligence: longitudinal relaxation time (T1) and magnetisation transfer ratio. Substantial correlations among 12 major white matter tracts studied allowed the extraction of three general factors of biomarker-specific brain-wide white matter tract integrity. Each was independently associated with general intelligence, together explaining 10% of the variance, and their effect was completely mediated by information-processing speed. Unlike most previously established neurostructural correlates of intelligence, these findings suggest a functionally plausible model of intelligence, where structurally intact axonal fibres across the brain provide the neuroanatomical infrastructure for fast information processing within widespread brain networks, supporting general intelligence.

  17. Stress, neurotransmitters, corticosterone and body-brain integration.

    PubMed

    Mora, Francisco; Segovia, Gregorio; Del Arco, Alberto; de Blas, Marta; Garrido, Pedro

    2012-10-02

    Stress can be defined as a brain-body reaction towards stimuli arising from the environment or from internal cues that are interpreted as a disruption of homeostasis. The organization of the response to a stressful situation involves not only the activity of different types of neurotransmitter systems in several areas of the limbic system, but also the response of neurons in these areas to several other chemicals and hormones, chiefly glucocorticoids, released from peripheral organs and glands. Thus, stress is probably the process through which body-brain integration plays a major role. Here we review first the responses to an acute stress in terms of neurotransmitters such as dopamine, acetylcholine, glutamate and GABA in areas of the brain involved in the regulation of stress responses. These areas include the prefrontal cortex, amygdala, hippocampus and nucleus accumbens and the interaction among those areas. Then, we consider the role of glucocorticoids and review some recent data about the interaction of these steroids with several neurotransmitters in those same areas of the brain. Also the actions of other substances (neuromodulators) released from peripheral organs such as the pancreas, liver or gonads (insulin, IGF-1, estrogens) are reviewed. The role of an environmental enrichment on these same responses is also discussed. Finally a section is devoted to put into perspective all these environmental-brain-body-brain interactions during stress and their consequences on aging. It is concluded that the integrative perspective framed in this review is relevant for better understanding of how the organism responds to stressful challenges and how this can be modified through different environmental conditions during the process of aging. This article is part of a Special Issue entitled: Brain Integration.

  18. An Embodied Brain Model of the Human Foetus

    PubMed Central

    Yamada, Yasunori; Kanazawa, Hoshinori; Iwasaki, Sho; Tsukahara, Yuki; Iwata, Osuke; Yamada, Shigehito; Kuniyoshi, Yasuo

    2016-01-01

    Cortical learning via sensorimotor experiences evoked by bodily movements begins as early as the foetal period. However, the learning mechanisms by which sensorimotor experiences guide cortical learning remain unknown owing to technical and ethical difficulties. To bridge this gap, we present an embodied brain model of a human foetus as a coupled brain-body-environment system by integrating anatomical/physiological data. Using this model, we show how intrauterine sensorimotor experiences related to bodily movements induce specific statistical regularities in somatosensory feedback that facilitate cortical learning of body representations and subsequent visual-somatosensory integration. We also show how extrauterine sensorimotor experiences affect these processes. Our embodied brain model can provide a novel computational approach to the mechanistic understanding of cortical learning based on sensorimotor experiences mediated by complex interactions between the body, environment and nervous system. PMID:27302194

  19. Exercise maintains blood-brain barrier integrity during early stages of brain metastasis formation.

    PubMed

    Wolff, Gretchen; Davidson, Sarah J; Wrobel, Jagoda K; Toborek, Michal

    2015-08-07

    Tumor cell extravasation into the brain requires passage through the blood-brain barrier, which is a highly protected microvascular environment fortified with tight junction (TJ) proteins. TJ integrity can be regulated under physiological and pathophysiological conditions. There is evidence that exercise can modulate oxidation status within the brain microvasculature and protect against tumor cell extravasation and metastasis formation. In order to study these events, mature male mice were given access to voluntary exercise on a running wheel (exercise) or access to a locked wheel (sedentary) for five weeks. The average running distance was 9.0 ± 0.2 km/day. Highly metastatic tumor cells (murine Lewis lung carcinoma) were then infused into the brain microvasculature through the internal carotid artery. Analyses were performed at early stage (48 h) and late stage (3 weeks) post tumor cell infusion. Immunohistochemical analysis revealed fewer isolated tumor cells extravasating into the brain at both 48 h and 3 weeks post surgery in exercised mice. Occludin protein levels were reduced in the sedentary tumor group, but maintained in the exercised tumor group at 48 h post tumor cell infusion. These results indicate that voluntary exercise may participate in modulating blood-brain barrier integrity thereby protecting the brain during metastatic progression.

  20. Chronic systemic IL-1β exacerbates central neuroinflammation independently of the blood-brain barrier integrity.

    PubMed

    Murta, Verónica; Farías, María Isabel; Pitossi, Fernando Juan; Ferrari, Carina Cintia

    2015-01-15

    Peripheral circulating cytokines are involved in immune to brain communication and systemic inflammation is considered a risk factor for flaring up the symptoms in most neurodegenerative diseases. We induced both central inflammatory demyelinating lesion, and systemic inflammation with an interleukin-1β expressing adenovector. The peripheral pro-inflammatory stimulus aggravated the ongoing central lesion independently of the blood-brain barrier (BBB) integrity. This model allows studying the role of specific molecules and cells (neutrophils) from the innate immune system, in the relationship between central and peripheral communication, and on relapsing episodes of demyelinating lesions, along with the role of BBB integrity.

  1. Physical Activity Affects Brain Integrity in HIV + Individuals

    PubMed Central

    Ortega, Mario; Baker, Laurie M.; Vaida, Florin; Paul, Robert; Basco, Brian; Ances, Beau M.

    2015-01-01

    Prior research has suggested benefits of aerobic physical activity (PA) on cognition and brain volumes in HIV uninfected (HIV−) individuals, however, few studies have explored the relationships between PA and brain integrity (cognition and structural brain volumes) in HIV-infected (HIV +) individuals. Seventy HIV + individuals underwent neuropsychological testing, structural neuroimaging, laboratory tests, and completed a PA questionnaire, recalling participation in walking, running, and jogging activities over the last year. A PA engagement score of weekly metabolic equivalent (MET) hr of activity was calculated using a compendium of PAs. HIV + individuals were classified as physically active (any energy expended above resting expenditure, n = 22) or sedentary (n = 48). Comparisons of neuropsychological performance, grouped by executive and motor domains, and brain volumes were completed between groups. Physically active and sedentary HIV + individuals had similar demographic and laboratory values, but the active group had higher education (14.0 vs. 12.6 years, p = .034). Physically active HIV + individuals performed better on executive (p = .040, unadjusted; p = .043, adjusted) but not motor function (p = .17). In addition, among the physically active group the amount of physical activity (METs) positively correlated with executive (Pearson’s r = 0.45, p = 0.035) but not motor (r = 0.21; p = .35) performance. In adjusted analyses the physically active HIV + individuals had larger putamen volumes (p = .019). A positive relationship exists between PA and brain integrity in HIV + individuals. Results from the present study emphasize the importance to conduct longitudinal interventional investigation to determine if PA improves brain integrity in HIV + individuals. PMID:26581799

  2. Integrated genomic and epigenomic analysis of breast cancer brain metastasis.

    PubMed

    Salhia, Bodour; Kiefer, Jeff; Ross, Julianna T D; Metapally, Raghu; Martinez, Rae Anne; Johnson, Kyle N; DiPerna, Danielle M; Paquette, Kimberly M; Jung, Sungwon; Nasser, Sara; Wallstrom, Garrick; Tembe, Waibhav; Baker, Angela; Carpten, John; Resau, Jim; Ryken, Timothy; Sibenaller, Zita; Petricoin, Emanuel F; Liotta, Lance A; Ramanathan, Ramesh K; Berens, Michael E; Tran, Nhan L

    2014-01-01

    The brain is a common site of metastatic disease in patients with breast cancer, which has few therapeutic options and dismal outcomes. The purpose of our study was to identify common and rare events that underlie breast cancer brain metastasis. We performed deep genomic profiling, which integrated gene copy number, gene expression and DNA methylation datasets on a collection of breast brain metastases. We identified frequent large chromosomal gains in 1q, 5p, 8q, 11q, and 20q and frequent broad-level deletions involving 8p, 17p, 21p and Xq. Frequently amplified and overexpressed genes included ATAD2, BRAF, DERL1, DNMTRB and NEK2A. The ATM, CRYAB and HSPB2 genes were commonly deleted and underexpressed. Knowledge mining revealed enrichment in cell cycle and G2/M transition pathways, which contained AURKA, AURKB and FOXM1. Using the PAM50 breast cancer intrinsic classifier, Luminal B, Her2+/ER negative, and basal-like tumors were identified as the most commonly represented breast cancer subtypes in our brain metastasis cohort. While overall methylation levels were increased in breast cancer brain metastasis, basal-like brain metastases were associated with significantly lower levels of methylation. Integrating DNA methylation data with gene expression revealed defects in cell migration and adhesion due to hypermethylation and downregulation of PENK, EDN3, and ITGAM. Hypomethylation and upregulation of KRT8 likely affects adhesion and permeability. Genomic and epigenomic profiling of breast brain metastasis has provided insight into the somatic events underlying this disease, which have potential in forming the basis of future therapeutic strategies.

  3. A model for brain life history evolution.

    PubMed

    González-Forero, Mauricio; Faulwasser, Timm; Lehmann, Laurent

    2017-03-01

    Complex cognition and relatively large brains are distributed across various taxa, and many primarily verbal hypotheses exist to explain such diversity. Yet, mathematical approaches formalizing verbal hypotheses would help deepen the understanding of brain and cognition evolution. With this aim, we combine elements of life history and metabolic theories to formulate a metabolically explicit mathematical model for brain life history evolution. We assume that some of the brain's energetic expense is due to production (learning) and maintenance (memory) of energy-extraction skills (or cognitive abilities, knowledge, information, etc.). We also assume that individuals use such skills to extract energy from the environment, and can allocate this energy to grow and maintain the body, including brain and reproductive tissues. The model can be used to ask what fraction of growth energy should be allocated at each age, given natural selection, to growing brain and other tissues under various biological settings. We apply the model to find uninvadable allocation strategies under a baseline setting ("me vs nature"), namely when energy-extraction challenges are environmentally determined and are overcome individually but possibly with maternal help, and use modern-human data to estimate model's parameter values. The resulting uninvadable strategies yield predictions for brain and body mass throughout ontogeny and for the ages at maturity, adulthood, and brain growth arrest. We find that: (1) a me-vs-nature setting is enough to generate adult brain and body mass of ancient human scale and a sequence of childhood, adolescence, and adulthood stages; (2) large brains are favored by intermediately challenging environments, moderately effective skills, and metabolically expensive memory; and (3) adult skill is proportional to brain mass when metabolic costs of memory saturate the brain metabolic rate allocated to skills.

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

    PubMed

    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.

  5. Integration of epidemiology, immunobiology, and translational research for brain tumors.

    PubMed

    Okada, Hideho; Scheurer, Michael E; Sarkar, Saumendra N; Bondy, Melissa L

    2013-05-01

    We recently identified a pivotal role for the host type I interferon (IFN) pathway in immunosurveillance against de novo mouse glioma development, especially through the regulation of immature myeloid cells (IMCs) in the glioma microenvironment. The present paper summarizes our published work in a number of areas. We have identified single-nucleotide polymorphisms (SNPs) in human IFN genes that dictate altered prognosis of patients with glioma. One of these SNPs (rs12553612) is located in the promoter of IFNA8 and influences its activity. Conversely, recent epidemiologic data show that chronic use of nonsteroidal anti-inflammatory drugs lowers the risk of glioma. We translated these findings back to our de novo glioma model and found that cyclooxygenase-2 inhibition enhances antiglioma immunosurveillance by reducing glioma-associated IMCs. Taken together, these findings suggest that alterations in myeloid cell function condition the brain for glioma development. Finally, in preliminary work, we have begun applying novel immunotherapeutic approaches to patients with low-grade glioma with the aim of preventing malignant transformation. Future research will hopefully better integrate epidemiological, immunobiological, and translational techniques to develop novel, preventive approaches for malignant gliomas.

  6. An Adaptive Complex Network Model for Brain Functional Networks

    PubMed Central

    Gomez Portillo, Ignacio J.; Gleiser, Pablo M.

    2009-01-01

    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. PMID:19738902

  7. Computational modeling of brain tumors: discrete, continuum or hybrid?

    NASA Astrophysics Data System (ADS)

    Wang, Zhihui; Deisboeck, Thomas S.

    In spite of all efforts, patients diagnosed with highly malignant brain tumors (gliomas), continue to face a grim prognosis. Achieving significant therapeutic advances will also require a more detailed quantitative understanding of the dynamic interactions among tumor cells, and between these cells and their biological microenvironment. Data-driven computational brain tumor models have the potential to provide experimental tumor biologists with such quantitative and cost-efficient tools to generate and test hypotheses on tumor progression, and to infer fundamental operating principles governing bidirectional signal propagation in multicellular cancer systems. This review highlights the modeling objectives of and challenges with developing such in silico brain tumor models by outlining two distinct computational approaches: discrete and continuum, each with representative examples. Future directions of this integrative computational neuro-oncology field, such as hybrid multiscale multiresolution modeling are discussed.

  8. Branes and integrable lattice models

    NASA Astrophysics Data System (ADS)

    Yagi, Junya

    2017-01-01

    This is a brief review of my work on the correspondence between four-dimensional 𝒩 = 1 supersymmetric field theories realized by brane tilings and two-dimensional integrable lattice models. I explain how to construct integrable lattice models from extended operators in partially topological quantum field theories, and elucidate the correspondence as an application of this construction.

  9. A model for brain life history evolution

    PubMed Central

    Lehmann, Laurent

    2017-01-01

    Complex cognition and relatively large brains are distributed across various taxa, and many primarily verbal hypotheses exist to explain such diversity. Yet, mathematical approaches formalizing verbal hypotheses would help deepen the understanding of brain and cognition evolution. With this aim, we combine elements of life history and metabolic theories to formulate a metabolically explicit mathematical model for brain life history evolution. We assume that some of the brain’s energetic expense is due to production (learning) and maintenance (memory) of energy-extraction skills (or cognitive abilities, knowledge, information, etc.). We also assume that individuals use such skills to extract energy from the environment, and can allocate this energy to grow and maintain the body, including brain and reproductive tissues. The model can be used to ask what fraction of growth energy should be allocated at each age, given natural selection, to growing brain and other tissues under various biological settings. We apply the model to find uninvadable allocation strategies under a baseline setting (“me vs nature”), namely when energy-extraction challenges are environmentally determined and are overcome individually but possibly with maternal help, and use modern-human data to estimate model’s parameter values. The resulting uninvadable strategies yield predictions for brain and body mass throughout ontogeny and for the ages at maturity, adulthood, and brain growth arrest. We find that: (1) a me-vs-nature setting is enough to generate adult brain and body mass of ancient human scale and a sequence of childhood, adolescence, and adulthood stages; (2) large brains are favored by intermediately challenging environments, moderately effective skills, and metabolically expensive memory; and (3) adult skill is proportional to brain mass when metabolic costs of memory saturate the brain metabolic rate allocated to skills. PMID:28278153

  10. Integrability of the Rabi Model

    SciTech Connect

    Braak, D.

    2011-09-02

    The Rabi model is a paradigm for interacting quantum systems. It couples a bosonic mode to the smallest possible quantum model, a two-level system. I present the analytical solution which allows us to consider the question of integrability for quantum systems that do not possess a classical limit. A criterion for quantum integrability is proposed which shows that the Rabi model is integrable due to the presence of a discrete symmetry. Moreover, I introduce a generalization with no symmetries; the generalized Rabi model is the first example of a nonintegrable but exactly solvable system.

  11. Pediatric Rodent Models of Traumatic Brain Injury.

    PubMed

    Semple, Bridgette D; Carlson, Jaclyn; Noble-Haeusslein, Linda J

    2016-01-01

    Due to a high incidence of traumatic brain injury (TBI) in children and adolescents, age-specific studies are necessary to fully understand the long-term consequences of injuries to the immature brain. Preclinical and translational research can help elucidate the vulnerabilities of the developing brain to insult, and provide model systems to formulate and evaluate potential treatments aimed at minimizing the adverse effects of TBI. Several experimental TBI models have therefore been scaled down from adult rodents for use in juvenile animals. The following chapter discusses these adapted models for pediatric TBI, and the importance of age equivalence across species during model development and interpretation. Many neurodevelopmental processes are ongoing throughout childhood and adolescence, such that neuropathological mechanisms secondary to a brain insult, including oxidative stress, metabolic dysfunction and inflammation, may be influenced by the age at the time of insult. The long-term evaluation of clinically relevant functional outcomes is imperative to better understand the persistence and evolution of behavioral deficits over time after injury to the developing brain. Strategies to modify or protect against the chronic consequences of pediatric TBI, by supporting the trajectory of normal brain development, have the potential to improve quality of life for brain-injured children.

  12. Integrated Models in Education.

    ERIC Educational Resources Information Center

    Butler-Por, Nava

    1979-01-01

    Examines educational change in Israeli junior high schools which was intended to integrate ethnic, social, and ability groups into a single national entity. Topics discussed include peer tutoring, busing, tutorial work given by gifted students to slow learners, and student motivation. Journal availability: see SO 507 297. (DB)

  13. Integrated Computational Model Development

    DTIC Science & Technology

    2014-03-01

    specific material properties. 15. SUBJECT TERMS alloy design, microstructure, mechanical properties, fatigue behavior, crack growth behavior...microstructure, processing, constitution, or alloy might not be correct. A critical piece of ICME is the “integration.” For years materials laboratories...experimental techniques. These four areas are explained in more detail below. Alloy Selection Processing Microstructure Lifing Properties Life Prediction Risk

  14. Multiregional integration in the brain during resting-state fMRI activity.

    PubMed

    Hay, Etay; Ritter, Petra; Lobaugh, Nancy J; McIntosh, Anthony R

    2017-03-01

    Data-driven models of functional magnetic resonance imaging (fMRI) activity can elucidate dependencies that involve the combination of multiple brain regions. Activity in some regions during resting-state fMRI can be predicted with high accuracy from the activities of other regions. However, it remains unclear in which regions activity depends on unique integration of multiple predictor regions. To address this question, sparse (parsimonious) models could serve to better determine key interregional dependencies by reducing false positives. We used resting-state fMRI data from 46 subjects, and for each region of interest (ROI) per subject we performed whole-brain recursive feature elimination (RFE) to select the minimal set of ROIs that best predicted activity in the modeled ROI. We quantified the dependence of activity on multiple predictor ROIs, by measuring the gain in prediction accuracy of models that incorporated multiple predictor ROIs compared to models that used a single predictor ROI. We identified regions that showed considerable evidence of multiregional integration and determined the key regions that contributed to their observed activity. Our models reveal fronto-parietal integration networks, little integration in primary sensory regions, as well as redundancy between some regions. Our study demonstrates the utility of whole-brain RFE to generate data-driven models with minimal sets of ROIs that predict activity with high accuracy. By determining the extent to which activity in each ROI depended on integration of signals from multiple ROIs, we find cortical integration networks during resting-state activity.

  15. Multiregional integration in the brain during resting-state fMRI activity

    PubMed Central

    Ritter, Petra; Lobaugh, Nancy J.; McIntosh, Anthony R.

    2017-01-01

    Data-driven models of functional magnetic resonance imaging (fMRI) activity can elucidate dependencies that involve the combination of multiple brain regions. Activity in some regions during resting-state fMRI can be predicted with high accuracy from the activities of other regions. However, it remains unclear in which regions activity depends on unique integration of multiple predictor regions. To address this question, sparse (parsimonious) models could serve to better determine key interregional dependencies by reducing false positives. We used resting-state fMRI data from 46 subjects, and for each region of interest (ROI) per subject we performed whole-brain recursive feature elimination (RFE) to select the minimal set of ROIs that best predicted activity in the modeled ROI. We quantified the dependence of activity on multiple predictor ROIs, by measuring the gain in prediction accuracy of models that incorporated multiple predictor ROIs compared to models that used a single predictor ROI. We identified regions that showed considerable evidence of multiregional integration and determined the key regions that contributed to their observed activity. Our models reveal fronto-parietal integration networks, little integration in primary sensory regions, as well as redundancy between some regions. Our study demonstrates the utility of whole-brain RFE to generate data-driven models with minimal sets of ROIs that predict activity with high accuracy. By determining the extent to which activity in each ROI depended on integration of signals from multiple ROIs, we find cortical integration networks during resting-state activity. PMID:28248957

  16. Ventral tegmental area/substantia nigra and prefrontal cortex rodent organotypic brain slices as an integrated model to study the cellular changes induced by oxygen/glucose deprivation and reperfusion: effect of neuroprotective agents.

    PubMed

    Colombo, Laura; Parravicini, Chiara; Lecca, Davide; Dossi, Elena; Heine, Claudia; Cimino, Mauro; Wanke, Enzo; Illes, Peter; Franke, Heike; Abbracchio, Maria P

    2014-01-01

    Unveiling the roles of distinct cell types in brain response to insults is a partially unsolved challenge and a key issue for new neuroreparative approaches. In vivo models are not able to dissect the contribution of residential microglia and infiltrating blood-borne monocytes/macrophages, which are fundamentally undistinguishable; conversely, cultured cells lack original tissue anatomical and functional complexity, which profoundly alters reactivity. Here, we tested whether rodent organotypic co-cultures from mesencephalic ventral tegmental area/substantia nigra and prefrontal cortex (VTA/SN-PFC) represent a suitable model to study changes induced by oxygen/glucose deprivation and reperfusion (OGD/R). OGD/R induced cytotoxicity to both VTA/SN and PFC slices, with higher VTA/SN susceptibility. Neurons were highly affected, with astrocytes and oligodendrocytes undergoing very mild damage. Marked reactive astrogliosis was also evident. Notably, OGD/R triggered the activation of CD68-expressing microglia and increased expression of Ym1 and Arg1, two markers of "alternatively" activated beneficial microglia. Treatment with two well-known neuroprotective drugs, the anticonvulsant agent valproic acid and the purinergic P2-antagonist PPADS, prevented neuronal damage. Thus, VTA/SN-PFC cultures are an integrated model to investigate OGD/R-induced effects on distinct cells and easily screen neuroprotective agents. The model is particularly adequate to dissect the microglia phenotypic shift in the lack of a functional vascular compartment.

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

    PubMed

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

    2004-07-22

    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 of the integration of letters and speech sounds using functional magnetic resonance imaging (fMRI). Letters and speech sounds were presented unimodally and bimodally in congruent or incongruent combinations. Analysis of single-subject data and group data aligned on the basis of individual cortical anatomy revealed that letters and speech sounds are integrated in heteromodal superior temporal cortex. Interestingly, responses to speech sounds in a modality-specific region of the early auditory cortex were modified by simultaneously presented letters. These results suggest that efficient processing of culturally defined associations between letters and speech sounds relies on neural mechanisms similar to those naturally evolved for integrating audiovisual speech.

  18. Affective state and community integration after traumatic brain injury.

    PubMed

    Juengst, Shannon B; Arenth, Patricia M; Raina, Ketki D; McCue, Michael; Skidmore, Elizabeth R

    2014-12-01

    Previous studies investigating the relationship between affective state and community integration have focused primarily on the influence of depression and anxiety. In addition, they have focused on frequency of participation in various activities, failing to address an individual's subjective satisfaction with participation. The purpose of this study was to examine how affective state contributes to frequency of participation and satisfaction with participation after traumatic brain injury among participants with and without a current major depressive episode. Sixty-four community-dwelling participants with a history of complicated mild-to-severe traumatic brain injury participated in this cross-sectional cohort study. High positive affect contributed significantly to frequency of participation (β = 0.401, P = 0.001), and both high positive affect and low negative affect significantly contributed to better satisfaction with participation (F2,61 = 13.63, P < 0.001). Further investigation to assess the direction of these relationships may better inform effective targets for intervention. These findings highlight the importance of assessing affective state after traumatic brain injury and incorporating a subjective measure of participation when considering community integration outcomes.

  19. Integrated undergraduate research experience for the study of brain injury.

    PubMed

    Barnes, Clifford L; Sierra, Michelle; Delay, Eugene R

    2003-01-01

    We developed a series of hands-on laboratory exercises on "Brain Injury" designed around several pedagogical goals that included the development of: 1) knowledge of the scientific method, 2) student problem solving skills by testing cause and effect relationships, 3) student analytical and critical thinking skills by evaluating and interpreting data, identifying alternative explanations for data, and identifying confounding variables, and 4) student writing skills by reporting their findings in manuscript form. Students, facilitated by the instructor, developed a testable hypothesis on short-term effects of brain injury by analyzing lesion size and astrocytic activity. Four sequential laboratory exercises were used to present and practice ablation techniques, histological processing, microscopic visualization and image-capture, and computer aided image analysis. This exercise culminated in a laboratory report that mimicked a research article. The effectiveness of the laboratory sequence was assessed by measuring the acquisition of 1) content on anatomical, physiological, and cellular responses of the brain to traumatic brain injury, and 2) laboratory skills and methods of data-collection and analysis using surgical procedures, histology, microscopy, and image analysis. Post-course test scores, significantly greater than pre-course test scores and greater than scores from a similar but unstructured laboratory class, indicated that this hands-on approach to teaching an undergraduate research laboratory was successful. Potential variations in the integrated laboratory exercise, including multidisciplinary collaborations, are also noted.

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

    PubMed

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

    2016-09-02

    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.

  1. Understanding How Exercise Promotes Cognitive Integrity in the Aging Brain.

    PubMed

    Laitman, Benjamin M; John, Gareth R

    2015-01-01

    Alterations in the structure and organization of the aging central nervous system (CNS), and associated functional deficits, result in cognitive decline and increase susceptibility to neurodegeneration. Age-related changes to the neurovascular unit (NVU), and their consequences for cerebrovascular function, are implicated as driving cognitive impairment during aging as well as in neurodegenerative disease. The molecular events underlying these effects are incompletely characterized. Similarly, the mechanisms underlying effects of factors that reduce the impact of aging on the brain, such as physical exercise, are also opaque. A study in this issue of PLOS Biology links the NVU to cognitive decline in the aging brain and suggests a potential underlying molecular mechanism. Notably, the study further links the protective effects of chronic exercise on cognition to neurovascular integrity during aging.

  2. 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.

    NASA Astrophysics Data System (ADS)

    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.

  3. Integrated Workforce Modeling System

    NASA Technical Reports Server (NTRS)

    Moynihan, Gary P.

    2000-01-01

    There are several computer-based systems, currently in various phases of development at KSC, which encompass some component, aspect, or function of workforce modeling. These systems may offer redundant capabilities and/or incompatible interfaces. A systems approach to workforce modeling is necessary in order to identify and better address user requirements. This research has consisted of two primary tasks. Task 1 provided an assessment of existing and proposed KSC workforce modeling systems for their functionality and applicability to the workforce planning function. Task 2 resulted in the development of a proof-of-concept design for a systems approach to workforce modeling. The model incorporates critical aspects of workforce planning, including hires, attrition, and employee development.

  4. Neural and Cognitive Modeling with Networks of Leaky Integrator Units

    NASA Astrophysics Data System (ADS)

    Graben, Peter beim; Liebscher, Thomas; Kurths, Jürgen

    After reviewing several physiological findings on oscillations in the electroencephalogram (EEG) and their possible explanations by dynamical modeling, we present neural networks consisting of leaky integrator units as a universal paradigm for neural and cognitive modeling. In contrast to standard recurrent neural networks, leaky integrator units are described by ordinary differential equations living in continuous time. We present an algorithm to train the temporal behavior of leaky integrator networks by generalized back-propagation and discuss their physiological relevance. Eventually, we show how leaky integrator units can be used to build oscillators that may serve as models of brain oscillations and cognitive processes.

  5. Integrable discrete PT symmetric model.

    PubMed

    Ablowitz, Mark J; Musslimani, Ziad H

    2014-09-01

    An exactly solvable discrete PT invariant nonlinear Schrödinger-like model is introduced. It is an integrable Hamiltonian system that exhibits a nontrivial nonlinear PT symmetry. A discrete one-soliton solution is constructed using a left-right Riemann-Hilbert formulation. It is shown that this pure soliton exhibits unique features such as power oscillations and singularity formation. The proposed model can be viewed as a discretization of a recently obtained integrable nonlocal nonlinear Schrödinger equation.

  6. White matter integrity supports BOLD signal variability and cognitive performance in the aging human brain.

    PubMed

    Burzynska, Agnieszka Z; Wong, Chelsea N; Voss, Michelle W; Cooke, Gillian E; McAuley, Edward; Kramer, Arthur F

    2015-01-01

    Decline in cognitive performance in old age is linked to both suboptimal neural processing in grey matter (GM) and reduced integrity of white matter (WM), but the whole-brain structure-function-cognition associations remain poorly understood. Here we apply a novel measure of GM processing-moment-to-moment variability in the blood oxygenation level-dependent signal (SDBOLD)-to study the associations between GM function during resting state, performance on four main cognitive domains (i.e., fluid intelligence, perceptual speed, episodic memory, vocabulary), and WM microstructural integrity in 91 healthy older adults (aged 60-80 years). We modeled the relations between whole-GM SDBOLD with cognitive performance using multivariate partial least squares analysis. We found that greater SDBOLD was associated with better fluid abilities and memory. Most of regions showing behaviorally relevant SDBOLD (e.g., precuneus and insula) were localized to inter- or intra-network "hubs" that connect and integrate segregated functional domains in the brain. Our results suggest that optimal dynamic range of neural processing in hub regions may support cognitive operations that specifically rely on the most flexible neural processing and complex cross-talk between different brain networks. Finally, we demonstrated that older adults with greater WM integrity in all major WM tracts had also greater SDBOLD and better performance on tests of memory and fluid abilities. We conclude that SDBOLD is a promising functional neural correlate of individual differences in cognition in healthy older adults and is supported by overall WM integrity.

  7. An integrative model of the maturation of cognitive control.

    PubMed

    Luna, Beatriz; Marek, Scott; Larsen, Bart; Tervo-Clemmens, Brenden; Chahal, Rajpreet

    2015-07-08

    Brains systems undergo unique and specific dynamic changes at the cellular, circuit, and systems level that underlie the transition to adult-level cognitive control. We integrate literature from these different levels of analyses to propose a novel model of the brain basis of the development of cognitive control. The ability to consistently exert cognitive control improves into adulthood as the flexible integration of component processes, including inhibitory control, performance monitoring, and working memory, increases. Unique maturational changes in brain structure, supported by interactions between dopaminergic and GABAergic systems, contribute to enhanced network synchronization and an improved signal-to-noise ratio. In turn, these factors facilitate the specialization and strengthening of connectivity in networks supporting the transition to adult levels of cognitive control. This model provides a novel understanding of the adolescent period as an adaptive period of heightened experience-seeking necessary for the specialization of brain systems supporting cognitive control.

  8. Integrated modeling for the VLTI

    NASA Astrophysics Data System (ADS)

    Muller, Michael; Wilhelm, Rainer C.; Baier, Horst J.; Koch, Franz

    2004-07-01

    Within the scope of the Very Large Telescope Interferometer (VLTI) project, ESO has developed a software package for integrated modeling of single- and multi-aperture optical telescopes. Integrated modeling is aiming at time-dependent system analysis combining different technical disciplines (optics, mechanical structure, control system with sensors and actuators, environmental disturbances). This allows multi-disciplinary analysis and gives information about cross-coupling effects for system engineering of complex stellar interferometers and telescopes. At the moment the main components of the Integrated Modeling Toolbox are BeamWarrior, a numerical tool for optical analysis of single- and multi-aperture telescopes, and the Structural Modeling Interface, which allows to generate Simulink blocks with reduced size from Finite Element Models of a telescope structure. Based on these tools, models of the various subsystems (e.g. telescope, delay line, beam combiner, atmosphere) can be created in the appropriate disciplines (e.g. optics, structure, disturbance). All subsystem models are integrated into the Matlab/Simulink environment for dynamic control system simulations. The basic output of the model is a complete description of the time-dependent electromagnetic field in each interferometer arm. Alternatively, a more elaborated output can be created, such as an interference fringe pattern at the focus of a beam combining instrument. The concern of this paper is the application of the modeling concept to large complex telescope systems. The concept of the Simulink-based integrated model with the main components telescope structure, optics and control loops is presented. The models for wind loads and atmospheric turbulence are explained. Especially the extension of the modeling approach to a 50 - 100 m class telescope is discussed.

  9. Whole Brain Radiotherapy With Hippocampal Avoidance and Simultaneously Integrated Brain Metastases Boost: A Planning Study

    SciTech Connect

    Gutierrez, Alonso N.; Westerly, David C.; Tome, Wolfgang A. Jaradat, Hazim A..; Mackie, Thomas R.; Bentzen, Soren M.; Khuntia, Deepak; Mehta, Minesh P.

    2007-10-01

    Purpose: To evaluate the feasibility of using tomotherapy to deliver whole brain radiotherapy with hippocampal avoidance, hypothesized to reduce the risk of memory function decline, and simultaneously integrated boost to brain metastases to improve intracranial tumor control. Methods and Materials: Ten patients treated with radiosurgery and whole brain radiotherapy underwent repeat planning using tomotherapy with the original computed tomography scans and magnetic resonance imaging-computed tomography fusion-defined target and normal structure contours. The individually contoured hippocampus was used as a dose-limiting structure (<6 Gy); the whole brain dose was prescribed at 32.25 Gy to 95% in 15 fractions, and the simultaneous boost doses to individual brain metastases were 63 Gy to lesions {>=}2.0 cm in the maximal diameter and 70.8 Gy to lesions <2.0 cm. The plans were generated with a field width (FW) of 2.5 cm and, in 5 patients, with a FW of 1.0 cm. The plans were compared regarding conformation number, prescription isodose/target volume ratio, target coverage, homogeneity index, and mean normalized total dose. Results: A 1.0-cm FW compared with a 2.5-cm FW significantly improved the dose distribution. The mean conformation number improved from 0.55 {+-} 0.16 to 0.60 {+-} 0.13. Whole brain homogeneity improved by 32% (p <0.001). The mean normalized total dose to the hippocampus was 5.9 {+-} 1.3 Gy{sub 2} and 5.8 {+-} 1.9 Gy{sub 2} for 2.5- and 1.0-cm FW, respectively. The mean treatment delivery time for the 2.5- and 1.0-cm FW plans was 10.2 {+-} 1.0 and 21.8 {+-} 1.8 min, respectively. Conclusion: Composite tomotherapy plans achieved three objectives: homogeneous whole brain dose distribution equivalent to conventional whole brain radiotherapy; conformal hippocampal avoidance; and radiosurgically equivalent dose distributions to individual metastases.

  10. Separations and safeguards model integration.

    SciTech Connect

    Cipiti, Benjamin B.; Zinaman, Owen

    2010-09-01

    Research and development of advanced reprocessing plant designs can greatly benefit from the development of a reprocessing plant model capable of transient solvent extraction chemistry. This type of model can be used to optimize the operations of a plant as well as the designs for safeguards, security, and safety. Previous work has integrated a transient solvent extraction simulation module, based on the Solvent Extraction Process Having Interaction Solutes (SEPHIS) code developed at Oak Ridge National Laboratory, with the Separations and Safeguards Performance Model (SSPM) developed at Sandia National Laboratory, as a first step toward creating a more versatile design and evaluation tool. The goal of this work was to strengthen the integration by linking more variables between the two codes. The results from this integrated model show expected operational performance through plant transients. Additionally, ORIGEN source term files were integrated into the SSPM to provide concentrations, radioactivity, neutron emission rate, and thermal power data for various spent fuels. This data was used to generate measurement blocks that can determine the radioactivity, neutron emission rate, or thermal power of any stream or vessel in the plant model. This work examined how the code could be expanded to integrate other separation steps and benchmark the results to other data. Recommendations for future work will be presented.

  11. Modelling Brain Temperature and Cerebral Cooling Methods

    NASA Astrophysics Data System (ADS)

    Blowers, Stephen; Valluri, Prashant; Marshall, Ian; Andrews, Peter; Harris, Bridget; Thrippleton, Michael

    2014-11-01

    Direct measurement of cerebral temperature is invasive and impractical meaning treatments for reduction of core brain temperature rely on predictive mathematical models. Current models rely on continuum equations which heavily simplify thermal interactions between blood and tissue. A novel two-phase 3D porous-fluid model is developed to address these limitations. The model solves porous flow equations in 3D along with energy transport equation in both the blood and tissue phases including metabolic generation. By incorporating geometry data extracted from MRI scans, 3D vasculature can be inserted into a porous brain structure to realistically represent blood distribution within the brain. Therefore, thermal transport and convective heat transfer of blood are solved by means of direct numerical simulations. In application, results show that external scalp cooling has a higher impact on both maximum and average core brain temperatures than previously predicted. Additionally, the extent of alternative treatment methods such as pharyngeal cooling and carotid infusion can be investigated using this model. Acknowledgement: EPSRC DTA.

  12. Compact continuum brain model for human electroencephalogram

    NASA Astrophysics Data System (ADS)

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

    2007-12-01

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

  13. Astrocytic laminin regulates pericyte differentiation and maintains blood brain barrier integrity

    NASA Astrophysics Data System (ADS)

    Yao, Yao; Chen, Zu-Lin; Norris, Erin H.; Strickland, Sidney

    2014-03-01

    Blood brain barrier (BBB) breakdown is not only a consequence of but also contributes to many neurological disorders, including stroke and Alzheimer’s disease. How the basement membrane (BM) contributes to the normal functioning of the BBB remains elusive. Here we use conditional knockout mice and an acute adenovirus-mediated knockdown model to show that lack of astrocytic laminin, a brain-specific BM component, induces BBB breakdown. Using functional blocking antibody and RNAi, we further demonstrate that astrocytic laminin, by binding to integrin α2 receptor, prevents pericyte differentiation from the BBB-stabilizing resting stage to the BBB-disrupting contractile stage, and thus maintains the integrity of BBB. Additionally, loss of astrocytic laminin decreases aquaporin-4 (AQP4) and tight junction protein expression. Altogether, we report a critical role for astrocytic laminin in BBB regulation and pericyte differentiation. These results indicate that astrocytic laminin maintains the integrity of BBB through, at least in part, regulation of pericyte differentiation.

  14. Antiretroviral Treatment with Efavirenz Disrupts the Blood-Brain Barrier Integrity and Increases Stroke Severity

    PubMed Central

    Bertrand, Luc; Dygert, Levi; Toborek, Michal

    2016-01-01

    The introduction of antiretroviral drugs (ARVd) changed the prognosis of HIV infection from a deadly disease to a chronic disease. However, even with undetectable viral loads, patients still develop a wide range of pathologies, including cerebrovascular complications and stroke. It is hypothesized that toxic side effects of ARVd may contribute to these effects. To address this notion, we evaluated the impact of several non-nucleoside reverse transcriptase inhibitors (NNRTI; Efavirenz, Etravirine, Rilpivirine and Nevirapine) on the integrity of the blood-brain barrier, and their impact on severity of stroke. Among studied drugs, Efavirenz, but not other NNRTIs, altered claudin-5 expression, increased endothelial permeability, and disrupted the blood-brain barrier integrity. Importantly, Efavirenz exposure increased the severity of stroke in a model of middle cerebral artery occlusion in mice. Taken together, these results indicate that selected ARVd can exacerbate HIV-associated cerebrovascular pathology. Therefore, careful consideration should be taken when choosing an anti-retroviral therapy regimen. PMID:28008980

  15. Empirical Movement Models for Brain Computer Interfaces.

    PubMed

    Matlack, Charles; Chizeck, Howard; Moritz, Chet T

    2016-06-30

    For brain-computer interfaces (BCIs) which provide the user continuous position control, there is little standardization of performance metrics or evaluative tasks. One candidate metric is Fitts's law, which has been used to describe aimed movements across a range of computer interfaces, and has recently been applied to BCI tasks. Reviewing selected studies, we identify two basic problems with Fitts's law: its predictive performance is fragile, and the estimation of 'information transfer rate' from the model is unsupported. Our main contribution is the adaptation and validation of an alternative model to Fitts's law in the BCI context. We show that the Shannon-Welford model outperforms Fitts's law, showing robust predictive power when target distance and width have disproportionate effects on difficulty. Building on a prior study of the Shannon-Welford model, we show that identified model parameters offer a novel approach to quantitatively assess the role of controldisplay gain in speed/accuracy performance tradeoffs during brain control.

  16. Modeling brain disease in a dish: really?

    PubMed

    Marchetto, Maria C; Gage, Fred H

    2012-06-14

    Cellular programming and reprogramming technology (CPART) presents a novel approach for understanding disease progression and mechanism. In addition, CPART provides an innovative opportunity for developing diagnostic tools and novel drug candidates for therapy. In this Forum, we will discuss obstacles and solutions for modeling brain disease using CPART.

  17. Angiotensin receptors and β-catenin regulate brain endothelial integrity in malaria

    PubMed Central

    Basu-Roy, Upal; Ty, Maureen; Alique, Matilde; Fernandez-Arias, Cristina; Movila, Alexandru; Gomes, Pollyanna; Edagha, Innocent; Wassmer, Samuel C.; Walther, Thomas

    2016-01-01

    Cerebral malaria is characterized by cytoadhesion of Plasmodium falciparum–infected red blood cells (Pf-iRBCs) to endothelial cells in the brain, disruption of the blood-brain barrier, and cerebral microhemorrhages. No available antimalarial drugs specifically target the endothelial disruptions underlying this complication, which is responsible for the majority of malaria-associated deaths. Here, we have demonstrated that ruptured Pf-iRBCs induce activation of β-catenin, leading to disruption of inter–endothelial cell junctions in human brain microvascular endothelial cells (HBMECs). Inhibition of β-catenin–induced TCF/LEF transcription in the nucleus of HBMECs prevented the disruption of endothelial junctions, confirming that β-catenin is a key mediator of P. falciparum adverse effects on endothelial integrity. Blockade of the angiotensin II type 1 receptor (AT1) or stimulation of the type 2 receptor (AT2) abrogated Pf-iRBC–induced activation of β-catenin and prevented the disruption of HBMEC monolayers. In a mouse model of cerebral malaria, modulation of angiotensin II receptors produced similar effects, leading to protection against cerebral malaria, reduced cerebral hemorrhages, and increased survival. In contrast, AT2-deficient mice were more susceptible to cerebral malaria. The interrelation of the β-catenin and the angiotensin II signaling pathways opens immediate host-targeted therapeutic possibilities for cerebral malaria and other diseases in which brain endothelial integrity is compromised. PMID:27643439

  18. Neurodynamical model of collective brain

    NASA Technical Reports Server (NTRS)

    Zak, Michail

    1992-01-01

    A dynamical system which mimics collective purposeful activities of a set of units of intelligence is introduced and discussed. A global control of the unit activities is replaced by the probabilistic correlations between them. These correlations are learned during a long term period of performing collective tasks, and are stored in the synaptic interconnections. The model is represented by a system of ordinary differential equations with terminal attractors and repellers, and does not contain any man-made digital devices.

  19. ITI: The Model. Integrated Thematic Instruction. Third Edition.

    ERIC Educational Resources Information Center

    Kovalik, Susan; Olsen, Karen

    This book presents Integrated Thematic Instruction (ITI), a model for implementing a "brain-compatible" learning environment for students and teachers using a year-long theme to organize curriculum content and skills. The book's introduction identifies six "mismemes" (or mistaken ideas) that have hindered educational reform,…

  20. Verbal Neuropsychological Functions in Aphasia: An Integrative Model

    ERIC Educational Resources Information Center

    Vigliecca, Nora Silvana; Báez, Sandra

    2015-01-01

    A theoretical framework which considers the verbal functions of the brain under a multivariate and comprehensive cognitive model was statistically analyzed. A confirmatory factor analysis was performed to verify whether some recognized aphasia constructs can be hierarchically integrated as latent factors from a homogenously verbal test. The Brief…

  1. Melatonin Preserves Blood-Brain Barrier Integrity and Permeability via Matrix Metalloproteinase-9 Inhibition

    PubMed Central

    Alluri, Himakarnika; Wilson, Rickesha L.; Anasooya Shaji, Chinchusha; Wiggins-Dohlvik, Katie; Patel, Savan; Liu, Yang; Peng, Xu; Beeram, Madhava R.; Davis, Matthew L.; Huang, Jason H.; Tharakan, Binu

    2016-01-01

    Microvascular hyperpermeability that occurs at the level of the blood-brain barrier (BBB) often leads to vasogenic brain edema and elevated intracranial pressure following traumatic brain injury (TBI). At a cellular level, tight junction proteins (TJPs) between neighboring endothelial cells maintain the integrity of the BBB via TJ associated proteins particularly, zonula occludens-1 (ZO-1) that binds to the transmembrane TJPs and actin cytoskeleton intracellularly. The pro-inflammatory cytokine, interleukin-1β (IL-1β) as well as the proteolytic enzymes, matrix metalloproteinase-9 (MMP-9) are key mediators of trauma-associated brain edema. Recent studies indicate that melatonin a pineal hormone directly binds to MMP-9 and also might act as its endogenous inhibitor. We hypothesized that melatonin treatment will provide protection against TBI-induced BBB hyperpermeability via MMP-9 inhibition. Rat brain microvascular endothelial cells grown as monolayers were used as an in vitro model of the BBB and a mouse model of TBI using a controlled cortical impactor was used for all in vivo studies. IL-1β (10 ng/mL; 2 hours)-induced endothelial monolayer hyperpermeability was significantly attenuated by melatonin (10 μg/mL; 1 hour), GM6001 (broad spectrum MMP inhibitor; 10 μM; 1 hour), MMP-9 inhibitor-1 (MMP-9 specific inhibitor; 5 nM; 1 hour) or MMP-9 siRNA transfection (48 hours) in vitro. Melatonin and MMP-9 inhibitor-1 pretreatment attenuated IL-1β-induced MMP-9 activity, loss of ZO-1 junctional integrity and f-actin stress fiber formation. IL-1β treatment neither affected ZO-1 protein or mRNA expression or cell viability. Acute melatonin treatment attenuated BBB hyperpermeability in a mouse controlled cortical impact model of TBI in vivo. In conclusion, one of the protective effects of melatonin against BBB hyperpermeability occurs due to enhanced BBB integrity via MMP-9 inhibition. In addition, acute melatonin treatment provides protection against BBB

  2. Integrated modeling: a look back

    NASA Astrophysics Data System (ADS)

    Briggs, Clark

    2015-09-01

    This paper discusses applications and implementation approaches used for integrated modeling of structural systems with optics over the past 30 years. While much of the development work focused on control system design, significant contributions were made in system modeling and computer-aided design (CAD) environments. Early work appended handmade line-of-sight models to traditional finite element models, such as the optical spacecraft concept from the ACOSS program. The IDEAS2 computational environment built in support of Space Station collected a wider variety of existing tools around a parametric database. Later, IMOS supported interferometer and large telescope mission studies at JPL with MATLAB modeling of structural dynamics, thermal analysis, and geometric optics. IMOS's predecessor was a simple FORTRAN command line interpreter for LQG controller design with additional functions that built state-space finite element models. Specialized language systems such as CAESY were formulated and prototyped to provide more complex object-oriented functions suited to control-structure interaction. A more recent example of optical modeling directly in mechanical CAD is used to illustrate possible future directions. While the value of directly posing the optical metric in system dynamics terms is well understood today, the potential payoff is illustrated briefly via project-based examples. It is quite likely that integrated structure thermal optical performance (STOP) modeling could be accomplished in a commercial off-the-shelf (COTS) tool set. The work flow could be adopted, for example, by a team developing a small high-performance optical or radio frequency (RF) instrument.

  3. Constitutive modelling of brain tissue: experiment and theory.

    PubMed

    Miller, K; Chinzei, K

    1997-01-01

    Recent developments in computer-integrated and robot-aided surgery--in particular, the emergence of automatic surgical tools and robots--as well as advances in virtual reality techniques, call for closer examination of the mechanical properties of very soft tissues (such as brain, liver, kidney, etc.). The ultimate goal of our research into the biomechanics of these tissues is the development of corresponding, realistic mathematical models. This paper contains experimental results of in vitro, uniaxial, unconfined compression of swine brain tissue and discusses a single-phase, non-linear, viscoelastic tissue model. The experimental results obtained for three loading velocities, ranging over five orders of magnitude, are presented. The applied strain rates have been much lower than those applied in previous studies, focused on injury modelling. The stress-strain curves are concave upward for all compression rates containing no linear portion from which a meaningful elastic modulus might be determined. The tissue response stiffened as the loading speed increased, indicating a strong stress-strain rate dependence. The use of the single-phase model is recommended for applications in registration, surgical operation planning and training systems as well as a control system of an image-guided surgical robot. The material constants for the brain tissue are evaluated. Agreement between the proposed theoretical model and experiment is good for compression levels reaching 30% and for loading velocities varying over five orders of magnitude.

  4. Multiscale modeling of brain blow flow

    NASA Astrophysics Data System (ADS)

    Karniadakis, George

    2014-11-01

    Cardiovascular pathologies, such as brain aneurysms, are affected by the global blood circulation as well as by the local microrheology. Hence, developing computational models for such cases requires the coupling of disparate spatial and temporal scales often governed by diverse mathematical descriptions, e.g., by partial differential equations (continuum, 3D or 1D) and ordinary differential equations for discrete particles (atomistic). However, interfacing atomistic-based with continuum-based domain discretizations is a challenging problem that requires both mathematical and computational advances. We will present a physical model of the brain vasculature consisting at the macro level of all major arteries (about 200 down to 0.5 mm), at the mesoscale the fractal arteriolar tree (more than 10 millions down to 20 nm) and at the microscale the capillary bed. Correspondingly, we employ three different methods to model the total brain vasculature by developing proper interface conditions at each level. We will present examples from aneurysms and other hematological diseases, where red blood cell rheology is modeled explicitly.

  5. White Matter Integrity Supports BOLD Signal Variability and Cognitive Performance in the Aging Human Brain

    PubMed Central

    Burzynska, Agnieszka Z.; Wong, Chelsea N.; Voss, Michelle W.; Cooke, Gillian E.; McAuley, Edward; Kramer, Arthur F.

    2015-01-01

    Decline in cognitive performance in old age is linked to both suboptimal neural processing in grey matter (GM) and reduced integrity of white matter (WM), but the whole-brain structure-function-cognition associations remain poorly understood. Here we apply a novel measure of GM processing–moment-to-moment variability in the blood oxygenation level-dependent signal (SDBOLD)—to study the associations between GM function during resting state, performance on four main cognitive domains (i.e., fluid intelligence, perceptual speed, episodic memory, vocabulary), and WM microstructural integrity in 91 healthy older adults (aged 60-80 years). We modeled the relations between whole-GM SDBOLD with cognitive performance using multivariate partial least squares analysis. We found that greater SDBOLD was associated with better fluid abilities and memory. Most of regions showing behaviorally relevant SDBOLD (e.g., precuneus and insula) were localized to inter- or intra-network “hubs” that connect and integrate segregated functional domains in the brain. Our results suggest that optimal dynamic range of neural processing in hub regions may support cognitive operations that specifically rely on the most flexible neural processing and complex cross-talk between different brain networks. Finally, we demonstrated that older adults with greater WM integrity in all major WM tracts had also greater SDBOLD and better performance on tests of memory and fluid abilities. We conclude that SDBOLD is a promising functional neural correlate of individual differences in cognition in healthy older adults and is supported by overall WM integrity. PMID:25853882

  6. Neurometric Modeling: Computational Modeling of Individual Brains

    DTIC Science & Technology

    2011-05-16

    Army Research Office P.O. Box 12211 Research Triangle Park, NC 27709-2211 15. SUBJECT TERMS Neural networks, computational neuroscience, fMRI ...obtained using functional MRI. Algorithmic processing of these measurements can exploit a variety of statistical machine learning methods to... statistical machine learning methods to synthesize a new kind of neuro-cognitive model, which we call neurometric models. These executable models could be

  7. The integrated environmental control model

    SciTech Connect

    Rubin, E.S.; Berkenpas, M.B.; Kalagnanam, J.R.

    1995-11-01

    The capability to estimate the performance and cost of emission control systems is critical to a variety of planning and analysis requirements faced by utilities, regulators, researchers and analysts in the public and private sectors. The computer model described in this paper has been developed for DOe to provide an up-to-date capability for analyzing a variety of pre-combustion, combustion, and post-combustion options in an integrated framework. A unique capability allows performance and costs to be modeled probabilistically, which allows explicit characterization of uncertainties and risks.

  8. Mouse Genetic Models of Human Brain Disorders

    PubMed Central

    Leung, Celeste; Jia, Zhengping

    2016-01-01

    Over the past three decades, genetic manipulations in mice have been used in neuroscience as a major approach to investigate the in vivo function of genes and their alterations. In particular, gene targeting techniques using embryonic stem cells have revolutionized the field of mammalian genetics and have been at the forefront in the generation of numerous mouse models of human brain disorders. In this review, we will first examine childhood developmental disorders such as autism, intellectual disability, Fragile X syndrome, and Williams-Beuren syndrome. We will then explore psychiatric disorders such as schizophrenia and lastly, neurodegenerative disorders including Alzheimer’s disease and Parkinson’s disease. We will outline the creation of these mouse models that range from single gene deletions, subtle point mutations to multi-gene manipulations, and discuss the key behavioral phenotypes of these mice. Ultimately, the analysis of the models outlined in this review will enhance our understanding of the in vivo role and underlying mechanisms of disease-related genes in both normal brain function and brain disorders, and provide potential therapeutic targets and strategies to prevent and treat these diseases. PMID:27047540

  9. Brain mechanisms of Change in Addictions Treatment: Models, Methods, and Emerging Findings.

    PubMed

    Chung, Tammy; Noronha, Antonio; Carroll, Kathleen M; Potenza, Marc N; Hutchison, Kent; Calhoun, Vince D; Gabrieli, John D E; Morgenstern, Jon; Nixon, Sara Jo; Wexler, Bruce E; Brewer, Judson; Ray, Lara; Filbey, Francesca; Strauman, Timothy J; Kober, Hedy; Feldstein Ewing, Sarah W

    2016-09-01

    Increased understanding of "how" and "for whom" treatment works at the level of the brain has potential to transform addictions treatment through the development of innovative neuroscience-informed interventions. The 2015 Science of Change meeting bridged the fields of neuroscience and psychotherapy research to identify brain mechanisms of behavior change that are "common" across therapies, and "specific" to distinct behavioral interventions. Conceptual models of brain mechanisms underlying effects of Cognitive Behavioral Therapy, mindfulness interventions, and Motivational Interviewing were discussed. Presentations covered methods for integrating neuroimaging into psychotherapy research, and novel analytic approaches. Effects of heavy substance use on the brain, and recovery of brain functioning with sustained abstinence, which may be facilitated by cognitive training, were reviewed. Neuroimaging provides powerful tools for determining brain mechanisms underlying psychotherapy and medication effects, predicting and monitoring outcomes, developing novel interventions that target specific brain circuits, and identifying for whom an intervention will be effective.

  10. Dynamic geometry, brain function modeling, and consciousness.

    PubMed

    Roy, Sisir; Llinás, Rodolfo

    2008-01-01

    Pellionisz and Llinás proposed, years ago, a geometric interpretation towards understanding brain function. This interpretation assumes that the relation between the brain and the external world is determined by the ability of the central nervous system (CNS) to construct an internal model of the external world using an interactive geometrical relationship between sensory and motor expression. This approach opened new vistas not only in brain research but also in understanding the foundations of geometry itself. The approach named tensor network theory is sufficiently rich to allow specific computational modeling and addressed the issue of prediction, based on Taylor series expansion properties of the system, at the neuronal level, as a basic property of brain function. It was actually proposed that the evolutionary realm is the backbone for the development of an internal functional space that, while being purely representational, can interact successfully with the totally different world of the so-called "external reality". Now if the internal space or functional space is endowed with stochastic metric tensor properties, then there will be a dynamic correspondence between events in the external world and their specification in the internal space. We shall call this dynamic geometry since the minimal time resolution of the brain (10-15 ms), associated with 40 Hz oscillations of neurons and their network dynamics, is considered to be responsible for recognizing external events and generating the concept of simultaneity. The stochastic metric tensor in dynamic geometry can be written as five-dimensional space-time where the fifth dimension is a probability space as well as a metric space. This extra dimension is considered an imbedded degree of freedom. It is worth noticing that the above-mentioned 40 Hz oscillation is present both in awake and dream states where the central difference is the inability of phase resetting in the latter. This framework of dynamic

  11. Cotangent Models for Integrable Systems

    NASA Astrophysics Data System (ADS)

    Kiesenhofer, Anna; Miranda, Eva

    2017-03-01

    We associate cotangent models to a neighbourhood of a Liouville torus in symplectic and Poisson manifolds focusing on b-Poisson/ b-symplectic manifolds. The semilocal equivalence with such models uses the corresponding action-angle theorems in these settings: the theorem of Liouville-Mineur-Arnold for symplectic manifolds and an action-angle theorem for regular Liouville tori in Poisson manifolds (Laurent- Gengoux et al., IntMath Res Notices IMRN 8: 1839-1869, 2011). Our models comprise regular Liouville tori of Poisson manifolds but also consider the Liouville tori on the singular locus of a b-Poisson manifold. For this latter class of Poisson structures we define a twisted cotangent model. The equivalence with this twisted cotangent model is given by an action-angle theorem recently proved by the authors and Scott (Math. Pures Appl. (9) 105(1):66-85, 2016). This viewpoint of cotangent models provides a new machinery to construct examples of integrable systems, which are especially valuable in the b-symplectic case where not many sources of examples are known. At the end of the paper we introduce non-degenerate singularities as lifted cotangent models on b-symplectic manifolds and discuss some generalizations of these models to general Poisson manifolds.

  12. Random Walks in Model Brain Tissue

    NASA Astrophysics Data System (ADS)

    Grinberg, Farida; Farrher, Ezequiel; Oros-Peusquens, Ana-Maria; Shah, N. Jon

    2011-03-01

    The propagation of water molecules in the brain and the corresponding NMR response are affected by many factors such as compartmentalization, restrictions and anisotropy imposed by the cellular microstructure. Interfacial interactions with cell membranes and exchange additionally come into play. Due to the complexity of the underlying factors, a differentiation between the various contributions to the average NMR signal in in vivo studies represents a difficult task. In this work we perform random-walk Monte Carlo simulations in well-defined model systems aiming at establishing quantitative relations between dynamics and microstructure. The results are compared with experimental data obtained for artificial anisotropic model systems.

  13. Server-based Approach to Web Visualization of Integrated Three-dimensional Brain Imaging Data

    PubMed Central

    Poliakov, Andrew V.; Albright, Evan; Hinshaw, Kevin P.; Corina, David P.; Ojemann, George; Martin, Richard F.; Brinkley, James F.

    2005-01-01

    The authors describe a client-server approach to three-dimensional (3-D) visualization of neuroimaging data, which enables researchers to visualize, manipulate, and analyze large brain imaging datasets over the Internet. All computationally intensive tasks are done by a graphics server that loads and processes image volumes and 3-D models, renders 3-D scenes, and sends the renderings back to the client. The authors discuss the system architecture and implementation and give several examples of client applications that allow visualization and analysis of integrated language map data from single and multiple patients. PMID:15561787

  14. Combining the boundary shift integral and tensor-based morphometry for brain atrophy estimation

    NASA Astrophysics Data System (ADS)

    Michalkiewicz, Mateusz; Pai, Akshay; Leung, Kelvin K.; Sommer, Stefan; Darkner, Sune; Sørensen, Lauge; Sporring, Jon; Nielsen, Mads

    2016-03-01

    Brain atrophy from structural magnetic resonance images (MRIs) is widely used as an imaging surrogate marker for Alzheimers disease. Their utility has been limited due to the large degree of variance and subsequently high sample size estimates. The only consistent and reasonably powerful atrophy estimation methods has been the boundary shift integral (BSI). In this paper, we first propose a tensor-based morphometry (TBM) method to measure voxel-wise atrophy that we combine with BSI. The combined model decreases the sample size estimates significantly when compared to BSI and TBM alone.

  15. The Center for Integrated Molecular Brain Imaging (Cimbi) database.

    PubMed

    Knudsen, Gitte M; Jensen, Peter S; Erritzoe, David; Baaré, William F C; Ettrup, Anders; Fisher, Patrick M; Gillings, Nic; Hansen, Hanne D; Hansen, Lars Kai; Hasselbalch, Steen G; Henningsson, Susanne; Herth, Matthias M; Holst, Klaus K; Iversen, Pernille; Kessing, Lars V; Macoveanu, Julian; Madsen, Kathrine Skak; Mortensen, Erik L; Nielsen, Finn Årup; Paulson, Olaf B; Siebner, Hartwig R; Stenbæk, Dea S; Svarer, Claus; Jernigan, Terry L; Strother, Stephen C; Frokjaer, Vibe G

    2016-01-01

    We here describe a multimodality neuroimaging containing data from healthy volunteers and patients, acquired within the Lundbeck Foundation Center for Integrated Molecular Brain Imaging (Cimbi) in Copenhagen, Denmark. The data is of particular relevance for neurobiological research questions related to the serotonergic transmitter system with its normative data on the serotonergic subtype receptors 5-HT1A, 5-HT1B, 5-HT2A, and 5-HT4 and the 5-HT transporter (5-HTT), but can easily serve other purposes. The Cimbi database and Cimbi biobank were formally established in 2008 with the purpose to store the wealth of Cimbi-acquired data in a highly structured and standardized manner in accordance with the regulations issued by the Danish Data Protection Agency as well as to provide a quality-controlled resource for future hypothesis-generating and hypothesis-driven studies. The Cimbi database currently comprises a total of 1100 PET and 1000 structural and functional MRI scans and it holds a multitude of additional data, such as genetic and biochemical data, and scores from 17 self-reported questionnaires and from 11 neuropsychological paper/computer tests. The database associated Cimbi biobank currently contains blood and in some instances saliva samples from about 500 healthy volunteers and 300 patients with e.g., major depression, dementia, substance abuse, obesity, and impulsive aggression. Data continue to be added to the Cimbi database and biobank.

  16. Endothelial Progenitor Cells Physiology and Metabolic Plasticity in Brain Angiogenesis and Blood-Brain Barrier Modeling

    PubMed Central

    Malinovskaya, Natalia A.; Komleva, Yulia K.; Salmin, Vladimir V.; Morgun, Andrey V.; Shuvaev, Anton N.; Panina, Yulia A.; Boitsova, Elizaveta B.; Salmina, Alla B.

    2016-01-01

    Currently, there is a considerable interest to the assessment of blood-brain barrier (BBB) development as a part of cerebral angiogenesis developmental program. Embryonic and adult angiogenesis in the brain is governed by the coordinated activity of endothelial progenitor cells, brain microvascular endothelial cells, and non-endothelial cells contributing to the establishment of the BBB (pericytes, astrocytes, neurons). Metabolic and functional plasticity of endothelial progenitor cells controls their timely recruitment, precise homing to the brain microvessels, and efficient support of brain angiogenesis. Deciphering endothelial progenitor cells physiology would provide novel engineering approaches to establish adequate microfluidically-supported BBB models and brain microphysiological systems for translational studies. PMID:27990124

  17. Sustained NMDA receptor hypofunction induces compromised neural systems integration and schizophrenia-like alterations in functional brain networks.

    PubMed

    Dawson, Neil; Xiao, Xiaolin; McDonald, Martin; Higham, Desmond J; Morris, Brian J; Pratt, Judith A

    2014-02-01

    Compromised functional integration between cerebral subsystems and dysfunctional brain network organization may underlie the neurocognitive deficits seen in psychiatric disorders. Applying topological measures from network science to brain imaging data allows the quantification of complex brain network connectivity. While this approach has recently been used to further elucidate the nature of brain dysfunction in schizophrenia, the value of applying this approach in preclinical models of psychiatric disease has not been recognized. For the first time, we apply both established and recently derived algorithms from network science (graph theory) to functional brain imaging data from rats treated subchronically with the N-methyl-D-aspartic acid (NMDA) receptor antagonist phencyclidine (PCP). We show that subchronic PCP treatment induces alterations in the global properties of functional brain networks akin to those reported in schizophrenia. Furthermore, we show that subchronic PCP treatment induces compromised functional integration between distributed neural systems, including between the prefrontal cortex and hippocampus, that have established roles in cognition through, in part, the promotion of thalamic dysconnectivity. We also show that subchronic PCP treatment promotes the functional disintegration of discrete cerebral subsystems and also alters the connectivity of neurotransmitter systems strongly implicated in schizophrenia. Therefore, we propose that sustained NMDA receptor hypofunction contributes to the pathophysiology of dysfunctional brain network organization in schizophrenia.

  18. An Integrated Vehicle Modeling Environment

    NASA Technical Reports Server (NTRS)

    Totah, Joseph J.; Kinney, David J.; Kaneshige, John T.; Agabon, Shane

    1999-01-01

    This paper describes an Integrated Vehicle Modeling Environment for estimating aircraft geometric, inertial, and aerodynamic characteristics, and for interfacing with a high fidelity, workstation based flight simulation architecture. The goals in developing this environment are to aid in the design of next generation intelligent fight control technologies, conduct research in advanced vehicle interface concepts for autonomous and semi-autonomous applications, and provide a value-added capability to the conceptual design and aircraft synthesis process. Results are presented for three aircraft by comparing estimates generated by the Integrated Vehicle Modeling Environment with known characteristics of each vehicle under consideration. The three aircraft are a modified F-15 with moveable canards attached to the airframe, a mid-sized, twin-engine commercial transport concept, and a small, single-engine, uninhabited aerial vehicle. Estimated physical properties and dynamic characteristics are correlated with those known for each aircraft over a large portion of the flight envelope of interest. These results represent the completion of a critical step toward meeting the stated goals for developing this modeling environment.

  19. Integrated Resource Planning Model (IRPM)

    SciTech Connect

    Graham, T. B.

    2010-04-01

    The Integrated Resource Planning Model (IRPM) is a decision-support software product for resource-and-capacity planning. Users can evaluate changing constraints on schedule performance, projected cost, and resource use. IRPM is a unique software tool that can analyze complex business situations from a basic supply chain to an integrated production facility to a distributed manufacturing complex. IRPM can be efficiently configured through a user-friendly graphical interface to rapidly provide charts, graphs, tables, and/or written results to summarize postulated business scenarios. There is not a similar integrated resource planning software package presently available. Many different businesses (from government to large corporations as well as medium-to-small manufacturing concerns) could save thousands of dollars and hundreds of labor hours in resource and schedule planning costs. Those businesses also could avoid millions of dollars of revenue lost from fear of overcommitting or from penalties and lost future business for failing to meet promised delivery by using IRPM to perform what-if business-case evaluations. Tough production planning questions that previously were left unanswered can now be answered with a high degree of certainty. Businesses can anticipate production problems and have solutions in hand to deal with those problems. IRPM allows companies to make better plans, decisions, and investments.

  20. Highlighting the structure-function relationship of the brain with the Ising model and graph theory.

    PubMed

    Das, T K; Abeyasinghe, P M; Crone, J S; Sosnowski, A; Laureys, S; Owen, A M; Soddu, A

    2014-01-01

    With the advent of neuroimaging techniques, it becomes feasible to explore the structure-function relationships in the brain. When the brain is not involved in any cognitive task or stimulated by any external output, it preserves important activities which follow well-defined spatial distribution patterns. Understanding the self-organization of the brain from its anatomical structure, it has been recently suggested to model the observed functional pattern from the structure of white matter fiber bundles. Different models which study synchronization (e.g., the Kuramoto model) or global dynamics (e.g., the Ising model) have shown success in capturing fundamental properties of the brain. In particular, these models can explain the competition between modularity and specialization and the need for integration in the brain. Graphing the functional and structural brain organization supports the model and can also highlight the strategy used to process and organize large amount of information traveling between the different modules. How the flow of information can be prevented or partially destroyed in pathological states, like in severe brain injured patients with disorders of consciousness or by pharmacological induction like in anaesthesia, will also help us to better understand how global or integrated behavior can emerge from local and modular interactions.

  1. Fractional Modeling of Viscoelasticity in Brain Aneurysms

    NASA Astrophysics Data System (ADS)

    Yu, Yue; Karniadakis, George

    2014-11-01

    We develop fundamental new numerical methods for fractional order PDEs, and investigate corresponding models for arterial walls. Specifically, the arterial wall is a heterogeneous soft tissue with complex biomechanical properties, and its constitutive laws are typically derived using integer-order differential equations. However, recent simulations on 1D model have indicated that fractional order models may offer a more powerful alternative for describing arterial wall mechanics, because they are less sensitive to the parameter estimation compared with the integer-calculus-based models. We study the specific fractional PDEs that better model the properties of the 3D arterial walls, and for the first time employ them in simulating flow structure interactions for patient-specific brain aneurysms. A comparison study indicates that for the integer order models, the viscous behavior strongly depends on the relaxation parameters while the fractional order models are less sensitive. This finding is consistent with what is observed in the 1D models for arterial networks (Perdikaris & Karniadakis, 2014), except that when the fractional order is small, the 3D fractional-order models are more sensitive to the fractional order compared to the 1D models.

  2. SyM-BBB: A Microfluidic Blood Brain Barrier Model

    PubMed Central

    Prabhakarpandian, Balabhaskar; Shen, Ming-Che; Nichols, Joseph B.; Mills, Ivy R.; Sidoryk-Wegrzynowicz, Marta; Aschner, Michael; Pant, Kapil

    2013-01-01

    Current techniques for mimicking the Blood-Brain Barrier (BBB) largely use incubation chambers (Transwell) separated with a filter and matrix coating to represent and to study barrier permeability. These devices have several critical shortcomings; (a) they do not reproduce critical microenvironmental parameters, primarily anatomical size or hemodynamic shear stress, (b) they often do not provide real-time visualization capability, and (c) they require a large amount of consumables. To overcome these limitations, we have developed a microfluidics based Synthetic Microvasculature model of the Blood-Brain Barrier (SyM-BBB). The SyM-BBB platform is comprised of a plastic, disposable and optically clear microfluidic chip with a microcirculation sized two-compartment chamber. The chamber is designed in such a way as to permit the realization of side-by-side apical and basolateral compartments, thereby simplifying fabrication and facilitating integration with standard instrumentation. The individually addressable apical side is seeded with endothelial cells and the basolateral side can support neuronal cells or conditioned media. In the present study, an immortalized Rat Brain Endothelial cell line (RBE4) was cultured in SyM-BBB with a perfusate of Astrocyte Conditioned Media (ACM). Biochemical analysis showed upregulation of tight junction molecules while permeation studies showed an intact BBB. Finally, transporter assay was successfully demonstrated in SyM-BBB indicating a functional model. PMID:23344641

  3. Adaptive Urban Dispersion Integrated Model

    SciTech Connect

    Wissink, A; Chand, K; Kosovic, B; Chan, S; Berger, M; Chow, F K

    2005-11-03

    Numerical simulations represent a unique predictive tool for understanding the three-dimensional flow fields and associated concentration distributions from contaminant releases in complex urban settings (Britter and Hanna 2003). Utilization of the most accurate urban models, based on fully three-dimensional computational fluid dynamics (CFD) that solve the Navier-Stokes equations with incorporated turbulence models, presents many challenges. We address two in this work; first, a fast but accurate way to incorporate the complex urban terrain, buildings, and other structures to enforce proper boundary conditions in the flow solution; second, ways to achieve a level of computational efficiency that allows the models to be run in an automated fashion such that they may be used for emergency response and event reconstruction applications. We have developed a new integrated urban dispersion modeling capability based on FEM3MP (Gresho and Chan 1998, Chan and Stevens 2000), a CFD model from Lawrence Livermore National Lab. The integrated capability incorporates fast embedded boundary mesh generation for geometrically complex problems and full three-dimensional Cartesian adaptive mesh refinement (AMR). Parallel AMR and embedded boundary gridding support are provided through the SAMRAI library (Wissink et al. 2001, Hornung and Kohn 2002). Embedded boundary mesh generation has been demonstrated to be an automatic, fast, and efficient approach for problem setup. It has been used for a variety of geometrically complex applications, including urban applications (Pullen et al. 2005). The key technology we introduce in this work is the application of AMR, which allows the application of high-resolution modeling to certain important features, such as individual buildings and high-resolution terrain (including important vegetative and land-use features). It also allows the urban scale model to be readily interfaced with coarser resolution meso or regional scale models. This talk

  4. Modeling the brain with laser diodes

    NASA Astrophysics Data System (ADS)

    McAulay, Alastair D.

    2007-09-01

    The Wilson-Cowan mathematical model is popular for representing a neuron in the brain and may be viewed as two cross-coupled dynamical nonlinear neural networks, one excitatory and one inhibitory. This gives rise to two coupled first order equations. Varying an input parameter, the sum of input intensities from all other incoming neurons, causes the Wilson-Cowan neural oscillator to move through a supercritical Hopf bifurcation so as to switch its output from a stable-off when the input is below a firing threshold to a stable-oscillation (limit cycle) for signals above the threshold; the frequency of which depends on the level of input stimulation. The use of frequency to represent pulse rate makes the brain robust against electromagnetic interference and drift. We show that the laser diode rate equations for a single optically injected laser diode can also be modeled by two coupled first order equations that give rise to supercritical Hopf bifurcations. But the laser rate equations have a complex variable where that for the Wilson-Cowan model equations is real. By using the real part of the complex variable (a projection onto the real plane), the optically injected laser diode can exactly simulate the movement through supercritical Hopf bifurcation of the Wilson-Cowan equations by varying the amplitude and frequency of the optical injection.

  5. Animal models of traumatic brain injury

    PubMed Central

    Xiong, Ye; Mahmood, Asim; Chopp, Michael

    2014-01-01

    Traumatic brain injury (TBI) is a leading cause of mortality and morbidity in both civilian life and the battlefield worldwide. Survivors of TBI frequently experience long-term disabling changes in cognition, sensorimotor function and personality. Over the past three decades, animal models have been developed to replicate the various aspects of human TBI, to better understand the underlying pathophysiology and to explore potential treatments. Nevertheless, promising neuroprotective drugs, which were identified to be effective in animal TBI models, have all failed in phase II or phase III clinical trials. This failure in clinical translation of preclinical studies highlights a compelling need to revisit the current status of animal models of TBI and therapeutic strategies. PMID:23329160

  6. On a Quantum Model of Brain Activities

    NASA Astrophysics Data System (ADS)

    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. Why Brains Matter: An Integrational Perspective on "The Symbolic Species."

    ERIC Educational Resources Information Center

    Cowley, Stephen J.

    2002-01-01

    Argues that Deacon's coevolutionary theory provides a basis for changing how we think about language and brains. Instead of ascribing language to either nature or nurture, it is seen as intrinsic to both: biological principles ensure the brain can only function by attuning to its body's worlds. (Author/VWL)

  8. An integrated modelling framework for neural circuits with multiple neuromodulators

    PubMed Central

    Vemana, Vinith

    2017-01-01

    Neuromodulators are endogenous neurochemicals that regulate biophysical and biochemical processes, which control brain function and behaviour, and are often the targets of neuropharmacological drugs. Neuromodulator effects are generally complex partly owing to the involvement of broad innervation, co-release of neuromodulators, complex intra- and extrasynaptic mechanism, existence of multiple receptor subtypes and high interconnectivity within the brain. In this work, we propose an efficient yet sufficiently realistic computational neural modelling framework to study some of these complex behaviours. Specifically, we propose a novel dynamical neural circuit model that integrates the effective neuromodulator-induced currents based on various experimental data (e.g. electrophysiology, neuropharmacology and voltammetry). The model can incorporate multiple interacting brain regions, including neuromodulator sources, simulate efficiently and easily extendable to large-scale brain models, e.g. for neuroimaging purposes. As an example, we model a network of mutually interacting neural populations in the lateral hypothalamus, dorsal raphe nucleus and locus coeruleus, which are major sources of neuromodulator orexin/hypocretin, serotonin and norepinephrine/noradrenaline, respectively, and which play significant roles in regulating many physiological functions. We demonstrate that such a model can provide predictions of systemic drug effects of the popular antidepressants (e.g. reuptake inhibitors), neuromodulator antagonists or their combinations. Finally, we developed user-friendly graphical user interface software for model simulation and visualization for both fundamental sciences and pharmacological studies. PMID:28100828

  9. Brain-skull boundary conditions in a computational deformation model

    NASA Astrophysics Data System (ADS)

    Ji, Songbai; Liu, Fenghong; Roberts, David; Hartov, Alex; Paulsen, Keith

    2007-03-01

    Brain shift poses a significant challenge to accurate image-guided neurosurgery. To this end, finite element (FE) brain models have been developed to estimate brain motion during these procedures. The significance of the brain-skull boundary conditions (BCs) for accurate predictions in these models has been explored in dynamic impact and inertial rotation injury computational simulations where the results have shown that the brain mechanical response is sensitive to the type of BCs applied. We extend the study of brain-skull BCs to quasi-static brain motion simulations which prevail in neurosurgery. Specifically, a frictionless brain-skull BC using a contact penalty method master-slave paradigm is incorporated into our existing deformation forward model (forced displacement method). The initial brain-skull gap (CSF thickness) is assumed to be 2mm for demonstration purposes. The brain surface nodes are assigned as either fixed (at bottom along the gravity direction), free (at brainstem), with prescribed displacement (at craniotomy) or as slave nodes potentially in contact with the skull (all the remaining). Each slave node is assigned a penalty parameter (β=5) such that when the node penetrates the rigid body skull inner-surface (master surface), a contact force is introduced proportionally to the penetration. Effectively, brain surface nodes are allowed to move towards or away from the cranium wall, but are ultimately restricted from penetrating the skull. We show that this scheme improves the model's ability to represent the brain-skull interface.

  10. Endothelial β-Catenin Signaling Is Required for Maintaining Adult Blood-Brain Barrier Integrity and CNS Homeostasis

    PubMed Central

    Tran, Khiem A.; Zhang, Xianming; Predescu, Dan; Huang, Xiaojia; Machado, Roberto F.; Göthert, Joachim R.; Malik, Asrar B.; Valyi-Nagy, Tibor; Zhao, You-Yang

    2015-01-01

    Background The blood-brain barrier (BBB) formed by brain endothelial cells (ECs) interconnected by tight junctions (TJs) is essential for the homeostasis of the central nervous system (CNS). Although studies have shown the importance of various signaling molecules in BBB formation during development, little is known about the molecular basis regulating the integrity of the adult BBB. Methods and Results Using a mouse model with tamoxifen-inducible EC-restricted disruption of ctnnb1 (iCKO), here we show that endothelial β-catenin signaling is essential for maintaining BBB integrity and CNS homeostasis in adult. The iCKO mice developed severe seizures accompanied by neuronal injury, multiple brain petechial hemorrhages, and CNS inflammation, and all died postictal. Disruption of endothelial β-catenin induced BBB breakdown and downregulation of specific TJ proteins Claudin-1 and -3 in adult brain ECs. The clinical relevance of the data is indicated by the observation of decreased expression of Claudin-1 and nuclear β-catenin in brain ECs of hemorrhagic lesions of hemorrhagic stroke patients. Conclusion These results demonstrate the prerequisite role of endothelial β-catenin in maintaining the integrity of adult BBB. The results suggest that BBB dysfunction secondary to defective β-catenin transcription activity is a key pathogenic factor in hemorrhagic stroke, seizure activity and CNS inflammation. PMID:26538583

  11. Multiscale modeling and simulation of brain blood flow

    SciTech Connect

    Perdikaris, Paris; Grinberg, Leopold; Karniadakis, George Em

    2016-02-15

    The aim of this work is to present an overview of recent advances in multi-scale modeling of brain blood flow. In particular, we present some approaches that enable the in silico study of multi-scale and multi-physics phenomena in the cerebral vasculature. We discuss the formulation of continuum and atomistic modeling approaches, present a consistent framework for their concurrent coupling, and list some of the challenges that one needs to overcome in achieving a seamless and scalable integration of heterogeneous numerical solvers. The effectiveness of the proposed framework is demonstrated in a realistic case involving modeling the thrombus formation process taking place on the wall of a patient-specific cerebral aneurysm. This highlights the ability of multi-scale algorithms to resolve important biophysical processes that span several spatial and temporal scales, potentially yielding new insight into the key aspects of brain blood flow in health and disease. Finally, we discuss open questions in multi-scale modeling and emerging topics of future research.

  12. Multiscale modeling and simulation of brain blood flow

    PubMed Central

    Perdikaris, Paris; Grinberg, Leopold; Karniadakis, George Em

    2016-01-01

    The aim of this work is to present an overview of recent advances in multi-scale modeling of brain blood flow. In particular, we present some approaches that enable the in silico study of multi-scale and multi-physics phenomena in the cerebral vasculature. We discuss the formulation of continuum and atomistic modeling approaches, present a consistent framework for their concurrent coupling, and list some of the challenges that one needs to overcome in achieving a seamless and scalable integration of heterogeneous numerical solvers. The effectiveness of the proposed framework is demonstrated in a realistic case involving modeling the thrombus formation process taking place on the wall of a patient-specific cerebral aneurysm. This highlights the ability of multi-scale algorithms to resolve important biophysical processes that span several spatial and temporal scales, potentially yielding new insight into the key aspects of brain blood flow in health and disease. Finally, we discuss open questions in multi-scale modeling and emerging topics of future research. PMID:26909005

  13. Multiscale modeling and simulation of brain blood flow.

    PubMed

    Perdikaris, Paris; Grinberg, Leopold; Karniadakis, George Em

    2016-02-01

    The aim of this work is to present an overview of recent advances in multi-scale modeling of brain blood flow. In particular, we present some approaches that enable the in silico study of multi-scale and multi-physics phenomena in the cerebral vasculature. We discuss the formulation of continuum and atomistic modeling approaches, present a consistent framework for their concurrent coupling, and list some of the challenges that one needs to overcome in achieving a seamless and scalable integration of heterogeneous numerical solvers. The effectiveness of the proposed framework is demonstrated in a realistic case involving modeling the thrombus formation process taking place on the wall of a patient-specific cerebral aneurysm. This highlights the ability of multi-scale algorithms to resolve important biophysical processes that span several spatial and temporal scales, potentially yielding new insight into the key aspects of brain blood flow in health and disease. Finally, we discuss open questions in multi-scale modeling and emerging topics of future research.

  14. An Integrated Neuroscience and Engineering Approach to Classifying Human Brain-States

    DTIC Science & Technology

    2015-12-22

    AFRL-AFOSR-VA-TR-2016-0037 An Integrated Neuroscience and Engineering Approach to Classifying Human Brain-States Adrian Lee UNIVERSITY OF WASHINGTON...to 14-09-2015 4. TITLE AND SUBTITLE An Integrated Neuroscience and Engineering Approach to Classifying Human Brain- States 5a.  CONTRACT NUMBER 5b...UNLIMITED: PB Public Release 13. SUPPLEMENTARY NOTES 14. ABSTRACT Harnessing the capability to read and classify brainwaves into the myriad of possible human

  15. Ex vivo Evans blue assessment of the blood brain barrier in three breast cancer brain metastasis models.

    PubMed

    Do, John; Foster, Deshka; Renier, Corinne; Vogel, Hannes; Rosenblum, Sahar; Doyle, Timothy C; Tse, Victor; Wapnir, Irene

    2014-02-01

    The limited entry of anticancer drugs into the central nervous system represents a special therapeutic challenge for patients with brain metastases and is primarily due to the blood brain barrier (BBB). Albumin-bound Evans blue (EB) dye is too large to cross the BBB but can grossly stain tissue blue when the BBB is disrupted. The course of tumor development and the integrity of the BBB were studied in three preclinical breast cancer brain metastasis (BCBM) models. A luciferase-transduced braintropic clone of MDA-231 cell line was used. Nude mice were subjected to stereotactic intracerebral inoculation, mammary fat pad-derived tumor fragment implantation, or carotid artery injections. EB was injected 30 min prior to euthanasia at various timepoints for each of the BCBM model animals. Serial bioluminescent imaging demonstrated exponential tumor growth in all models. Carotid BCBM appeared as diffuse multifocal cell clusters. EB aided the localization of metastases ex vivo. Tumor implants stained blue at 7 days whereas gross staining was not evident until day 14 in the stereotactic model and day 28 for the carotid model. EB assessment of the integrity of the BBB provides useful information relevant to drug testing in preclinical BCBM models.

  16. Integrated Urban Dispersion Modeling Capability

    SciTech Connect

    Kosovic, B; Chan, S T

    2003-11-03

    Numerical simulations represent a unique predictive tool for developing a detailed understanding of three-dimensional flow fields and associated concentration distributions from releases in complex urban settings (Britter and Hanna 2003). The accurate and timely prediction of the atmospheric dispersion of hazardous materials in densely populated urban areas is a critical homeland and national security need for emergency preparedness, risk assessment, and vulnerability studies. The main challenges in high-fidelity numerical modeling of urban dispersion are the accurate prediction of peak concentrations, spatial extent and temporal evolution of harmful levels of hazardous materials, and the incorporation of detailed structural geometries. Current computational tools do not include all the necessary elements to accurately represent hazardous release events in complex urban settings embedded in high-resolution terrain. Nor do they possess the computational efficiency required for many emergency response and event reconstruction applications. We are developing a new integrated urban dispersion modeling capability, able to efficiently predict dispersion in diverse urban environments for a wide range of atmospheric conditions, temporal and spatial scales, and release event scenarios. This new computational fluid dynamics capability includes adaptive mesh refinement and it can simultaneously resolve individual buildings and high-resolution terrain (including important vegetative and land-use features), treat complex building and structural geometries (e.g., stadiums, arenas, subways, airplane interiors), and cope with the full range of atmospheric conditions (e.g. stability). We are developing approaches for seamless coupling with mesoscale numerical weather prediction models to provide realistic forcing of the urban-scale model, which is critical to its performance in real-world conditions.

  17. Bryostatin-1 Restores Blood Brain Barrier Integrity following Blast-Induced Traumatic Brain Injury

    PubMed Central

    Lucke-Wold, Brandon P.; Logsdon, Aric F.; Smith, Kelly E.; Turner, Ryan C.; Alkon, Daniel L.; Tan, Zhenjun; Naser, Zachary J.; Knotts, Chelsea M.; Huber, Jason D.

    2016-01-01

    Recent wars in Iraq and Afghanistan have accounted for an estimated 270,000 blast exposures among military personnel. Blast traumatic brain injury (TBI) is the ‘signature injury’ of modern warfare. Blood brain barrier (BBB) disruption following blast TBI can lead to long-term and diffuse neuroinflammation. In this study, we investigate for the first time the role of bryostatin-1, a specific protein kinase C (PKC) modulator, in ameliorating BBB breakdown. Thirty seven Sprague–Dawley rats were used for this study. We utilized a clinically relevant and validated blast model to expose animals to moderate blast exposure. Groups included: control, single blast exposure, and single blast exposure + bryostatin-1. Bryostatin-1 was administered i.p. 2.5 mg/kg after blast exposure. Evan’s blue, immunohistochemistry, and western blot analysis were performed to assess injury. Evan’s blue binds to albumin and is a marker for BBB disruption. The single blast exposure caused an increase in permeability compared to control (t=4.808, p<0.05), and a reduction back toward control levels when bryostatin-1 was administered (t=5.113, p<0.01). Three important PKC isozymes, PKCα, PKCδ, and PKCε, were co-localized primarily with endothelial cells but not astrocytes. Bryostatin-1 administration reduced toxic PKCα levels back toward control levels (t=4.559, p<0.01) and increased the neuroprotective isozyme PKCε (t=6.102, p<0.01). Bryostatin-1 caused a significant increase in the tight junction proteins VE-cadherin, ZO-1, and occludin through modulation of PKC activity. Bryostatin-1 ultimately decreased BBB breakdown potentially due to modulation of PKC isozymes. Future work will examine the role of bryostatin-1 in preventing chronic neurodegeneration following repetitive neurotrauma. PMID:25301233

  18. Bryostatin-1 Restores Blood Brain Barrier Integrity following Blast-Induced Traumatic Brain Injury.

    PubMed

    Lucke-Wold, Brandon P; Logsdon, Aric F; Smith, Kelly E; Turner, Ryan C; Alkon, Daniel L; Tan, Zhenjun; Naser, Zachary J; Knotts, Chelsea M; Huber, Jason D; Rosen, Charles L

    2015-12-01

    Recent wars in Iraq and Afghanistan have accounted for an estimated 270,000 blast exposures among military personnel. Blast traumatic brain injury (TBI) is the 'signature injury' of modern warfare. Blood brain barrier (BBB) disruption following blast TBI can lead to long-term and diffuse neuroinflammation. In this study, we investigate for the first time the role of bryostatin-1, a specific protein kinase C (PKC) modulator, in ameliorating BBB breakdown. Thirty seven Sprague-Dawley rats were used for this study. We utilized a clinically relevant and validated blast model to expose animals to moderate blast exposure. Groups included: control, single blast exposure, and single blast exposure + bryostatin-1. Bryostatin-1 was administered i.p. 2.5 mg/kg after blast exposure. Evan's blue, immunohistochemistry, and western blot analysis were performed to assess injury. Evan's blue binds to albumin and is a marker for BBB disruption. The single blast exposure caused an increase in permeability compared to control (t = 4.808, p < 0.05), and a reduction back toward control levels when bryostatin-1 was administered (t = 5.113, p < 0.01). Three important PKC isozymes, PKCα, PKCδ, and PKCε, were co-localized primarily with endothelial cells but not astrocytes. Bryostatin-1 administration reduced toxic PKCα levels back toward control levels (t = 4.559, p < 0.01) and increased the neuroprotective isozyme PKCε (t = 6.102, p < 0.01). Bryostatin-1 caused a significant increase in the tight junction proteins VE-cadherin, ZO-1, and occludin through modulation of PKC activity. Bryostatin-1 ultimately decreased BBB breakdown potentially due to modulation of PKC isozymes. Future work will examine the role of bryostatin-1 in preventing chronic neurodegeneration following repetitive neurotrauma.

  19. Brain functional integration decreases during propofol-induced loss of consciousness.

    PubMed

    Schrouff, Jessica; Perlbarg, Vincent; Boly, Mélanie; Marrelec, Guillaume; Boveroux, Pierre; Vanhaudenhuyse, Audrey; Bruno, Marie-Aurélie; Laureys, Steven; Phillips, Christophe; Pélégrini-Issac, Mélanie; Maquet, Pierre; Benali, Habib

    2011-07-01

    Consciousness has been related to the amount of integrated information that the brain is able to generate. In this paper, we tested the hypothesis that the loss of consciousness caused by propofol anesthesia is associated with a significant reduction in the capacity of the brain to integrate information. To assess the functional structure of the whole brain, functional integration and partial correlations were computed from fMRI data acquired from 18 healthy volunteers during resting wakefulness and propofol-induced deep sedation. Total integration was significantly reduced from wakefulness to deep sedation in the whole brain as well as within and between its constituent networks (or systems). Integration was systematically reduced within each system (i.e., brain or networks), as well as between networks. However, the ventral attentional network maintained interactions with most other networks during deep sedation. Partial correlations further suggested that functional connectivity was particularly affected between parietal areas and frontal or temporal regions during deep sedation. Our findings suggest that the breakdown in brain integration is the neural correlate of the loss of consciousness induced by propofol. They stress the important role played by parietal and frontal areas in the generation of consciousness.

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

    PubMed Central

    2014-01-01

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

  1. INTEGRATED HYDROGEN STORAGE SYSTEM MODEL

    SciTech Connect

    Hardy, B

    2007-11-16

    Hydrogen storage is recognized as a key technical hurdle that must be overcome for the realization of hydrogen powered vehicles. Metal hydrides and their doped variants have shown great promise as a storage material and significant advances have been made with this technology. In any practical storage system the rate of H2 uptake will be governed by all processes that affect the rate of mass transport through the bed and into the particles. These coupled processes include heat and mass transfer as well as chemical kinetics and equilibrium. However, with few exceptions, studies of metal hydrides have focused primarily on fundamental properties associated with hydrogen storage capacity and kinetics. A full understanding of the complex interplay of physical processes that occur during the charging and discharging of a practical storage system requires models that integrate the salient phenomena. For example, in the case of sodium alanate, the size of NaAlH4 crystals is on the order of 300nm and the size of polycrystalline particles may be approximately 10 times larger ({approx}3,000nm). For the bed volume to be as small as possible, it is necessary to densely pack the hydride particles. Even so, in packed beds composed of NaAlH{sub 4} particles alone, it has been observed that the void fraction is still approximately 50-60%. Because of the large void fraction and particle to particle thermal contact resistance, the thermal conductivity of the hydride is very low, on the order of 0.2 W/m-{sup o}C, Gross, Majzoub, Thomas and Sandrock [2002]. The chemical reaction for hydrogen loading is exothermic. Based on the data in Gross [2003], on the order of 10{sup 8}J of heat of is released for the uptake of 5 kg of H{sub 2}2 and complete conversion of NaH to NaAlH{sub 4}. Since the hydride reaction transitions from hydrogen loading to discharge at elevated temperatures, it is essential to control the temperature of the bed. However, the low thermal conductivity of the hydride

  2. Modeling Brain Resonance Phenomena Using a Neural Mass Model

    PubMed Central

    Spiegler, Andreas; Knösche, Thomas R.; Schwab, Karin; Haueisen, Jens; Atay, Fatihcan M.

    2011-01-01

    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. PMID:22215992

  3. Is functional integration of resting state brain networks an unspecific biomarker for working memory performance?

    PubMed

    Alavash, Mohsen; Doebler, Philipp; Holling, Heinz; Thiel, Christiane M; Gießing, Carsten

    2015-03-01

    Is there one optimal topology of functional brain networks at rest from which our cognitive performance would profit? Previous studies suggest that functional integration of resting state brain networks is an important biomarker for cognitive performance. However, it is still unknown whether higher network integration is an unspecific predictor for good cognitive performance or, alternatively, whether specific network organization during rest predicts only specific cognitive abilities. Here, we investigated the relationship between network integration at rest and cognitive performance using two tasks that measured different aspects of working memory; one task assessed visual-spatial and the other numerical working memory. Network clustering, modularity and efficiency were computed to capture network integration on different levels of network organization, and to statistically compare their correlations with the performance in each working memory test. The results revealed that each working memory aspect profits from a different resting state topology, and the tests showed significantly different correlations with each of the measures of network integration. While higher global network integration and modularity predicted significantly better performance in visual-spatial working memory, both measures showed no significant correlation with numerical working memory performance. In contrast, numerical working memory was superior in subjects with highly clustered brain networks, predominantly in the intraparietal sulcus, a core brain region of the working memory network. Our findings suggest that a specific balance between local and global functional integration of resting state brain networks facilitates special aspects of cognitive performance. In the context of working memory, while visual-spatial performance is facilitated by globally integrated functional resting state brain networks, numerical working memory profits from increased capacities for local processing

  4. An Integrated Bayesian Model for DIF Analysis

    ERIC Educational Resources Information Center

    Soares, Tufi M.; Goncalves, Flavio B.; Gamerman, Dani

    2009-01-01

    In this article, an integrated Bayesian model for differential item functioning (DIF) analysis is proposed. The model is integrated in the sense of modeling the responses along with the DIF analysis. This approach allows DIF detection and explanation in a simultaneous setup. Previous empirical studies and/or subjective beliefs about the item…

  5. Mathematical modeling of human brain physiological data

    NASA Astrophysics Data System (ADS)

    Böhm, Matthias; Faltermeier, Rupert; Brawanski, Alexander; Lang, Elmar W.

    2013-12-01

    Recently, a mathematical model of the basic physiological processes regulating the cerebral perfusion and oxygen supply was introduced [Jung , J. Math. Biol.JMBLAJ0303-681210.1007/s00285-005-0343-5 51, 491 (2005)]. Although this model correctly describes the interdependence of arterial blood pressure (ABP) and intracranial pressure (ICP), it fails badly when it comes to explaining certain abnormal correlations seen in about 80% of the recordings of ABP together with ICP and the partial oxygen pressure (TiPO2) of the neuronal tissue, taken at an intensive care unit during neuromonitoring of patients with a severe brain trauma. Such recordings occasionally show segments, where the mean arterial blood pressure is correlated with the partial oxygen pressure in tissue but anticorrelated with the intracranial pressure. The origin of such abnormal correlations has not been fully understood yet. Here, two extensions to the previous approach are proposed which can reproduce such abnormal correlations in simulations quantitatively. Furthermore, as the simulations are based on a mathematical model, additional insight into the physiological mechanisms from which such abnormal correlations originate can be gained.

  6. A Supported Relationships Intervention to Increase the Social Integration of Persons with Traumatic Brain Injuries.

    ERIC Educational Resources Information Center

    Johnson, Katherine; Davis, Paula K.

    1998-01-01

    Three persons with traumatic brain injury (TBI) were matched with four community participants for leisure activities. Community participants were trained and were given specific interactions suggestions. Integrated social contacts were measured using a multiple-baseline design across participants. Results suggest that social integration can be…

  7. Bayesian network models in brain functional connectivity analysis

    PubMed Central

    Zhang, Sheng; Li, Chiang-shan R.

    2013-01-01

    Much effort has been made to better understand the complex integration of distinct parts of the human brain using functional magnetic resonance imaging (fMRI). Altered functional connectivity between brain regions is associated with many neurological and mental illnesses, such as Alzheimer and Parkinson diseases, addiction, and depression. In computational science, Bayesian networks (BN) have been used in a broad range of studies to model complex data set in the presence of uncertainty and when expert prior knowledge is needed. However, little is done to explore the use of BN in connectivity analysis of fMRI data. In this paper, we present an up-to-date literature review and methodological details of connectivity analyses using BN, while highlighting caveats in a real-world application. We present a BN model of fMRI dataset obtained from sixty healthy subjects performing the stop-signal task (SST), a paradigm widely used to investigate response inhibition. Connectivity results are validated with the extant literature including our previous studies. By exploring the link strength of the learned BN’s and correlating them to behavioral performance measures, this novel use of BN in connectivity analysis provides new insights to the functional neural pathways underlying response inhibition. PMID:24319317

  8. Modeling the brain-pituitary-gonad axis in salmon

    SciTech Connect

    Kim, Jonghan; Hayton, William L.; Schultz, Irv R.

    2006-08-24

    To better understand the complexity of the brain-pituitary-gonad axis (BPG) in fish, we developed a biologically based pharmacodynamic model capable of accurately predicting the normal functioning of the BPG axis in salmon. This first-generation model consisted of a set of 13 equations whose formulation was guided by published values for plasma concentrations of pituitary- (FSH, LH) and ovary- (estradiol, 17a,20b-dihydroxy-4-pregnene-3-one) derived hormones measured in Coho salmon over an annual spawning period. In addition, the model incorporated pertinent features of previously published mammalian models and indirect response pharmacodynamic models. Model-based equations include a description of gonadotropin releasing hormone (GnRH) synthesis and release from the hypothalamus, which is controlled by environmental variables such as photoperiod and water temperature. GnRH stimulated the biosynthesis of mRNA for FSH and LH, which were also influenced by estradiol concentration in plasma. The level of estradiol in the plasma was regulated by the oocytes, which moved along a maturation progression. Estradiol was synthesized at a basal rate and as oocytes matured, stimulation of its biosynthesis occurred. The BPG model can be integrated with toxico-genomic, -proteomic data, allowing linkage between molecular based biomarkers and reproduction in fish.

  9. Permeability of ergot alkaloids across the blood-brain barrier in vitro and influence on the barrier integrity

    PubMed Central

    Mulac, Dennis; Hüwel, Sabine; Galla, Hans-Joachim; Humpf, Hans-Ulrich

    2012-01-01

    Scope Ergot alkaloids are secondary metabolites of Claviceps spp. and they have been in the focus of research for many years. Experiments focusing on ergotamine as a former migraine drug referring to the ability to reach the brain revealed controversial results. The question to which extent ergot alkaloids are able to cross the blood-brain barrier is still not answered. Methods and results In order to answer this question we have studied the ability of ergot alkaloids to penetrate the blood-brain barrier in a well established in vitro model system using primary porcine brain endothelial cells. It could clearly be demonstrated that ergot alkaloids are able to cross the blood-brain barrier in high quantities in only a few hours. We could further identify an active transport for ergometrine as a substrate for the BCRP/ABCG2 transporter. Investigations concerning barrier integrity properties have identified ergocristinine as a potent substance to accumulate in these cells ultimately leading to a weakened barrier function. Conclusion For the first time we could show that the so far as biologically inactive described 8-(S) isomers of ergot alkaloids seem to have an influence on barrier integrity underlining the necessity for a risk assessment of ergot alkaloids in food and feed. PMID:22147614

  10. REVIEWS OF TOPICAL PROBLEMS: Models of neural dynamics in brain information processing — the developments of 'the decade'

    NASA Astrophysics Data System (ADS)

    Borisyuk, G. N.; Borisyuk, R. M.; Kazanovich, Yakov B.; Ivanitskii, Genrikh R.

    2002-10-01

    Neural network models are discussed that have been developed during the last decade with the purpose of reproducing spatio-temporal patterns of neural activity in different brain structures. The main goal of the modeling was to test hypotheses of synchronization, temporal and phase relations in brain information processing. The models being considered are those of temporal structure of spike sequences, of neural activity dynamics, and oscillatory models of attention and feature integration.

  11. PLATO: data-oriented approach to collaborative large-scale brain system modeling.

    PubMed

    Kannon, Takayuki; Inagaki, Keiichiro; Kamiji, Nilton L; Makimura, Kouji; Usui, Shiro

    2011-11-01

    The brain is a complex information processing system, which can be divided into sub-systems, such as the sensory organs, functional areas in the cortex, and motor control systems. In this sense, most of the mathematical models developed in the field of neuroscience have mainly targeted a specific sub-system. In order to understand the details of the brain as a whole, such sub-system models need to be integrated toward the development of a neurophysiologically plausible large-scale system model. In the present work, we propose a model integration library where models can be connected by means of a common data format. Here, the common data format should be portable so that models written in any programming language, computer architecture, and operating system can be connected. Moreover, the library should be simple so that models can be adapted to use the common data format without requiring any detailed knowledge on its use. Using this library, we have successfully connected existing models reproducing certain features of the visual system, toward the development of a large-scale visual system model. This library will enable users to reuse and integrate existing and newly developed models toward the development and simulation of a large-scale brain system model. The resulting model can also be executed on high performance computers using Message Passing Interface (MPI).

  12. Brain Wave Biofeedback: Benefits of Integrating Neurofeedback in Counseling

    ERIC Educational Resources Information Center

    Myers, Jane E.; Young, J. Scott

    2012-01-01

    Consistent with the "2009 Standards" of the Council for Accreditation of Counseling and Related Educational Programs, counselors must understand neurobiological behavior in individuals of all developmental levels. This requires understanding the brain and strategies for applying neurobiological concepts in counseling practice, training, and…

  13. The application of integrated knowledge-based systems for the Biomedical Risk Assessment Intelligent Network (BRAIN)

    NASA Technical Reports Server (NTRS)

    Loftin, Karin C.; Ly, Bebe; Webster, Laurie; Verlander, James; Taylor, Gerald R.; Riley, Gary; Culbert, Chris

    1992-01-01

    One of NASA's goals for long duration space flight is to maintain acceptable levels of crew health, safety, and performance. One way of meeting this goal is through BRAIN, an integrated network of both human and computer elements. BRAIN will function as an advisor to mission managers by assessing the risk of inflight biomedical problems and recommending appropriate countermeasures. Described here is a joint effort among various NASA elements to develop BRAIN and the Infectious Disease Risk Assessment (IDRA) prototype. The implementation of this effort addresses the technological aspects of knowledge acquisition, integration of IDRA components, the use of expert systems to automate the biomedical prediction process, development of a user friendly interface, and integration of IDRA and ExerCISys systems. Because C language, CLIPS and the X-Window System are portable and easily integrated, they were chosen ss the tools for the initial IDRA prototype.

  14. Finite difference time domain (FDTD) modeling of implanted deep brain stimulation electrodes and brain tissue.

    PubMed

    Gabran, S R I; Saad, J H; Salama, M M A; Mansour, R R

    2009-01-01

    This paper demonstrates the electromagnetic modeling and simulation of an implanted Medtronic deep brain stimulation (DBS) electrode using finite difference time domain (FDTD). The model is developed using Empire XCcel and represents the electrode surrounded with brain tissue assuming homogenous and isotropic medium. The model is created to study the parameters influencing the electric field distribution within the tissue in order to provide reference and benchmarking data for DBS and intra-cortical electrode development.

  15. An integrated model-based neurosurgical guidance system

    NASA Astrophysics Data System (ADS)

    Ji, Songbai; Fan, Xiaoyao; Fontaine, Kathryn; Hartov, Alex; Roberts, David; Paulsen, Keith

    2010-02-01

    Maximal tumor resection without damaging healthy tissue in open cranial surgeries is critical to the prognosis for patients with brain cancers. Preoperative images (e.g., preoperative magnetic resonance images (pMR)) are typically used for surgical planning as well as for intraoperative image-guidance. However, brain shift even at the start of surgery significantly compromises the accuracy of neuronavigation, if the deformation is not compensated for. Compensating for brain shift during surgical operation is, therefore, critical for improving the accuracy of image-guidance and ultimately, the accuracy of surgery. To this end, we have developed an integrated neurosurgical guidance system that incorporates intraoperative three-dimensional (3D) tracking, acquisition of volumetric true 3D ultrasound (iUS), stereovision (iSV) and computational modeling to efficiently generate model-updated MR image volumes for neurosurgical guidance. The system is implemented with real-time Labview to provide high efficiency in data acquisition as well as with Matlab to offer computational convenience in data processing and development of graphical user interfaces related to computational modeling. In a typical patient case, the patient in the operating room (OR) is first registered to pMR image volume. Sparse displacement data extracted from coregistered intraoperative US and/or stereovision images are employed to guide a computational model that is based on consolidation theory. Computed whole-brain deformation is then used to generate a model-updated MR image volume for subsequent surgical guidance. In this paper, we present the key modular components of our integrated, model-based neurosurgical guidance system.

  16. On a Mathematical Model of Brain Activities

    SciTech Connect

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

    2007-12-03

    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.

  17. Whole-Brain Radiotherapy With Simultaneous Integrated Boost to Multiple Brain Metastases Using Volumetric Modulated Arc Therapy

    SciTech Connect

    Lagerwaard, Frank J. Hoorn, Elles A.P. van der; Verbakel, Wilko; Haasbeek, Cornelis J.A.; Slotman, Ben J.; Senan, Suresh

    2009-09-01

    Purpose: Volumetric modulated arc therapy (RapidArc [RA]; Varian Medical Systems, Palo Alto, CA) allows for the generation of intensity-modulated dose distributions by use of a single gantry rotation. We used RA to plan and deliver whole-brain radiotherapy (WBRT) with a simultaneous integrated boost in patients with multiple brain metastases. Methods and Materials: Composite RA plans were generated for 8 patients, consisting of WBRT (20 Gy in 5 fractions) with an integrated boost, also 20 Gy in 5 fractions, to Brain metastases, and clinically delivered in 3 patients. Summated gross tumor volumes were 1.0 to 37.5 cm{sup 3}. RA plans were measured in a solid water phantom by use of Gafchromic films (International Specialty Products, Wayne, NJ). Results: Composite RA plans could be generated within 1 hour. Two arcs were needed to deliver the mean of 1,600 monitor units with a mean 'beam-on' time of 180 seconds. RA plans showed excellent coverage of planning target volume for WBRT and planning target volume for the boost, with mean volumes receiving at least 95% of the prescribed dose of 100% and 99.8%, respectively. The mean conformity index was 1.36. Composite plans showed much steeper dose gradients outside Brain metastases than plans with a conventional summation of WBRT and radiosurgery. Comparison of calculated and measured doses showed a mean gamma for double-arc plans of 0.30, and the area with a gamma larger than 1 was 2%. In-room times for clinical RA sessions were approximately 20 minutes for each patient. Conclusions: RA treatment planning and delivery of integrated plans of WBRT and boosts to multiple brain metastases is a rapid and accurate technique that has a higher conformity index than conventional summation of WBRT and radiosurgery boost.

  18. Mathematical modelling of blood-brain barrier failure and edema

    NASA Astrophysics Data System (ADS)

    Waters, Sarah; Lang, Georgina; Vella, Dominic; Goriely, Alain

    2015-11-01

    Injuries such as traumatic brain injury and stroke can result in increased blood-brain barrier permeability. This increase may lead to water accumulation in the brain tissue resulting in vasogenic edema. Although the initial injury may be localised, the resulting edema causes mechanical damage and compression of the vasculature beyond the original injury site. We employ a biphasic mixture model to investigate the consequences of blood-brain barrier permeability changes within a region of brain tissue and the onset of vasogenic edema. We find that such localised changes can indeed result in brain tissue swelling and that the type of damage that results (stress damage or strain damage) depends on the ability of the brain to clear edema fluid.

  19. Action and Language Mechanisms in the Brain: Data, Models and Neuroinformatics

    PubMed Central

    Bonaiuto, James J.; Bornkessel-Schlesewsky, Ina; Kemmerer, David; MacWhinney, Brian; Nielsen, Finn Årup; Oztop, Erhan

    2014-01-01

    We assess the challenges of studying action and language mechanisms in the brain, both singly and in relation to each other to provide a novel perspective on neuroinformatics, integrating the development of databases for encoding – separately or together – neurocomputational models and empirical data that serve systems and cognitive neuroscience. PMID:24234916

  20. S-values calculated from a tomographic head/brain model for brain imaging

    NASA Astrophysics Data System (ADS)

    Chao, Tsi-chian; Xu, X. George

    2004-11-01

    A tomographic head/brain model was developed from the Visible Human images and used to calculate S-values for brain imaging procedures. This model contains 15 segmented sub-regions including caudate nucleus, cerebellum, cerebral cortex, cerebral white matter, corpus callosum, eyes, lateral ventricles, lenses, lentiform nucleus, optic chiasma, optic nerve, pons and middle cerebellar peduncle, skull CSF, thalamus and thyroid. S-values for C-11, O-15, F-18, Tc-99m and I-123 have been calculated using this model and a Monte Carlo code, EGS4. Comparison of the calculated S-values with those calculated from the MIRD (1999) stylized head/brain model shows significant differences. In many cases, the stylized head/brain model resulted in smaller S-values (as much as 88%), suggesting that the doses to a specific patient similar to the Visible Man could have been underestimated using the existing clinical dosimetry.

  1. Impaired inter-hemispheric integration in bipolar disorder revealed using brain network analyses

    PubMed Central

    Leow, Alex; Ajilore, Olusola; Zhan, Liang; Arienzo, Donatello; GadElkarim, Johnson; Zhang, Aifeng; Moody, Teena; Van Horn, John; Feusner, Jamie; Kumar, Anand; Thompson, Paul; Altshuler, Lori

    2014-01-01

    Background This represents the first graph theory based brain network analysis study in bipolar disorder, a chronic and disabling psychiatric disorder characterized by severe mood swings. Many imaging studies have investigated white matter in bipolar disorder with results suggesting abnormal white matter structural integrity, particularly in the fronto-limbic and callosal systems. However, many inconsistencies remain in the literature, and no study to-date has conducted brain network analyses using a graph-theoretic approach. Methods We acquired 64-direction diffusion-weighted MRI on 25 euthymic bipolar I disorder subjects and 24 gender and age equivalent healthy subjects. White matter integrity measures including fractional anisotropy and mean diffusivity were compared in the whole brain. Additionally, structural connectivity matrices based on whole brain deterministic tractography were constructed followed by the computation of both global and local brain network measures. We also designed novel metrics to further probe inter-hemispheric integration. Results Network analyses revealed that the bipolar brain networks exhibited significantly longer characteristic path length, lower clustering coefficient, and lower global efficiency relative to those of controls. Further analyses revealed impaired inter-hemispheric but relatively preserved intra-hemispheric integration. These findings were supported by whole brain white matter analyses that revealed significantly lower integrity in the corpus callosum in bipolar subjects. There were also abnormalities in nodal network measures in structures within the limbic system, especially the left hippocampus, the left lateral orbito-frontal cortex, and the bilateral isthmus cingulate. Conclusions These results suggest abnormalities in structural network organization in bipolar disorder, particularly in inter-hemispheric integration and within the limbic system. PMID:23122540

  2. An Instructional Model for Integrating the Calculator.

    ERIC Educational Resources Information Center

    Berlin, Donna F.; White, Arthur L.

    1987-01-01

    The design, selection, and organization of instructional materials that integrate calculators are described in relation to a model based on movement and representational level. Instructional resources and advantages of the model are described. (MNS)

  3. Modeling Blast-Related Brain Injury

    DTIC Science & Technology

    2008-12-01

    02139 D. Moore Defense and Veterans Brain Injury Center (WRAMC) 6900 Georgia Ave. NW, Washington, DC 20307 L. Noels University of Liege Chemin des...chevreuils 1, B4000 Liege , Belgium ABSTRACT Recent military conflicts in Iraq and Afghanistan have highlighted the wartime effect of traumatic brain in

  4. Integrating some mind and brain views of transference: the phenomena.

    PubMed

    Levin, F M

    1997-01-01

    Because understanding the underpinnings of transferential learning allows the analyst to more effectively exploit transference in the clinical situation, as well as to advance psychoanalytic theory, the functions and mechanisms of transference phenomena in learning are subjected to an interdisciplinary analysis. Through transference the brain creates hierarchical databases that make emotional sense of the world, especially the world of human relationships. Transference plays a role in defense and resistance clinically; less explored but equally important is the adaptive potential of transference and its effect on an individual's readiness for structural change through the activation of working memory. Most investigators within psychoanalysis have not considered the importance of similarity judgments and memory priming, especially as these help to explain why transference and its proper handling are effective in treatment. Yet there are complex relationships among transference, similarity judgment, and memory priming that tie together psychoanalysis, cognitive psychology, and neurophysiology. Evidence increasingly suggests a relationship between transference and the transfer of knowledge between various content domains (databases) of mind and brain, which is essential to cognitive and emotional learning. There are indications as well that transference decisively facilitates learning readiness ("windows") in general by means of two of its components: free association and spontaneous (self-initiated) activity. The important question of which mind/brain mechanisms motivate transference is not yet understood comprehensively. However, Vygotsky's work on the zone of proximal development (ZPD), M.Stern's teleonomic theory, schema theory, and neural network theory offer further insights into what motivates transference.

  5. Galectin-1 suppresses methamphetamine induced neuroinflammation in human brain microvascular endothelial cells: Neuroprotective role in maintaining blood brain barrier integrity.

    PubMed

    Parikh, Neil U; Aalinkeel, R; Reynolds, J L; Nair, B B; Sykes, D E; Mammen, M J; Schwartz, S A; Mahajan, S D

    2015-10-22

    Methamphetamine (Meth) abuse can lead to the breakdown of the blood-brain barrier (BBB) integrity leading to compromised CNS function. The role of Galectins in the angiogenesis process in tumor-associated endothelial cells (EC) is well established; however no data are available on the expression of Galectins in normal human brain microvascular endothelial cells and their potential role in maintaining BBB integrity. We evaluated the basal gene/protein expression levels of Galectin-1, -3 and -9 in normal primary human brain microvascular endothelial cells (BMVEC) that constitute the BBB and examined whether Meth altered Galectin expression in these cells, and if Galectin-1 treatment impacted the integrity of an in-vitro BBB. Our results showed that BMVEC expressed significantly higher levels of Galectin-1 as compared to Galectin-3 and -9. Meth treatment increased Galectin-1 expression in BMVEC. Meth induced decrease in TJ proteins ZO-1, Claudin-3 and adhesion molecule ICAM-1 was reversed by Galectin-1. Our data suggests that Galectin-1 is involved in BBB remodeling and can increase levels of TJ proteins ZO-1 and Claudin-3 and adhesion molecule ICAM-1 which helps maintain BBB tightness thus playing a neuroprotective role. Galectin-1 is thus an important regulator of immune balance from neurodegeneration to neuroprotection, which makes it an important therapeutic agent/target in the treatment of drug addiction and other neurological conditions.

  6. Modeling brain circuitry over a wide range of scales

    PubMed Central

    Fua, Pascal; Knott, Graham W.

    2015-01-01

    If we are ever to unravel the mysteries of brain function at its most fundamental level, we will need a precise understanding of how its component neurons connect to each other. Electron Microscopes (EM) can now provide the nanometer resolution that is needed to image synapses, and therefore connections, while Light Microscopes (LM) see at the micrometer resolution required to model the 3D structure of the dendritic network. Since both the topology and the connection strength are integral parts of the brain's wiring diagram, being able to combine these two modalities is critically important. In fact, these microscopes now routinely produce high-resolution imagery in such large quantities that the bottleneck becomes automated processing and interpretation, which is needed for such data to be exploited to its full potential. In this paper, we briefly review the Computer Vision techniques we have developed at EPFL to address this need. They include delineating dendritic arbors from LM imagery, segmenting organelles from EM, and combining the two into a consistent representation. PMID:25904852

  7. Information integration: its relevance to brain function and consciousness.

    PubMed

    Tononi, G

    2010-09-01

    A proper understanding of cognitive functions cannot be achieved without an understanding of consciousness, both at the empirical and at the theoretical level. This paper argues that consciousness has to do with a system's capacity for information integration. In this approach, every causal mechanism capable of choosing among alternatives generates information, and information is integrated to the extent that it is generated by a system above and beyond its parts. The set of integrated informational relationships generated by a complex of mechanisms--its quale--specify both the quantity and the quality of experience. As argued below, depending on the causal structure of a system, information integration can reach a maximum value at a particular spatial and temporal grain size. It is also argued that changes in information integration reflect a system's ability to match the causal structure of the world, both on the input and the output side. After a brief review suggesting that this approach is consistent with several experimental and clinical observations, the paper concludes with some prospective remarks about the relevance of understanding information integration for analyzing cognitive function, both normal and pathological.

  8. Integration of visual and motor functional streams in the human brain.

    PubMed

    Sepulcre, Jorge

    2014-05-01

    A long-standing difficulty in brain research has been to disentangle how information flows across circuits composed by multiple local and distant cerebral areas. At the large-scale level, several brain imaging methods have contributed to the understanding of those circuits by capturing the covariance or coupling patterns of blood oxygen level-dependent (BOLD) activity between distributed brain regions. The hypothesis is that underlying information processes are closely associated to synchronized brain activity, and therefore to the functional connectivity structure of the human brain. In this study, we have used a recently developed method called stepwise functional connectivity analysis. Our results show that motor and visual connectivity merge in a multimodal integration network that links together perception, action and cognition in the human functional connectome.

  9. Dependence of normal brain integral dose and normal tissue complication probability on the prescription isodose values for γ-knife radiosurgery

    NASA Astrophysics Data System (ADS)

    Ma, Lijun

    2001-11-01

    A recent multi-institutional clinical study suggested possible benefits of lowering the prescription isodose lines for stereotactic radiosurgery procedures. In this study, we investigate the dependence of the normal brain integral dose and the normal tissue complication probability (NTCP) on the prescription isodose values for γ-knife radiosurgery. An analytical dose model was developed for γ-knife treatment planning. The dose model was commissioned by fitting the measured dose profiles for each helmet size. The dose model was validated by comparing its results with the Leksell gamma plan (LGP, version 5.30) calculations. The normal brain integral dose and the NTCP were computed and analysed for an ensemble of treatment cases. The functional dependence of the normal brain integral dose and the NCTP versus the prescribing isodose values was studied for these cases. We found that the normal brain integral dose and the NTCP increase significantly when lowering the prescription isodose lines from 50% to 35% of the maximum tumour dose. Alternatively, the normal brain integral dose and the NTCP decrease significantly when raising the prescribing isodose lines from 50% to 65% of the maximum tumour dose. The results may be used as a guideline for designing future dose escalation studies for γ-knife applications.

  10. Task switching in traumatic brain injury relates to cortico-subcortical integrity.

    PubMed

    Leunissen, Inge; Coxon, James P; Caeyenberghs, Karen; Michiels, Karla; Sunaert, Stefan; Swinnen, Stephan P

    2014-05-01

    Suppressing and flexibly adapting actions are a critical part of our daily behavioral repertoire. Traumatic brain injury (TBI) patients show clear impairments in this type of action control; however, the underlying mechanisms are poorly understood. Here, we tested whether white matter integrity of cortico-subcortical pathways could account for impairments in task switching, an important component of executive functioning. Twenty young adults with TBI and eighteen controls performed a switching task requiring attention to global versus local stimulus features. Diffusion weighted images were acquired and whole brain tract-based spatial statistics (TBSS) were used to explore where white matter damage was associated with switching impairment. A crossing fiber model and probabilistic tractography further identified the specific fiber populations. Relative to controls, patients with a history of TBI had a higher switch cost and were less accurate. The TBI group showed a widespread decline in fractional anisotropy (FA) throughout the TBSS skeleton. FA in the superior corona radiata showed a negative relationship with switch cost. More specifically, this involved cortico-subcortical loops with the (pre-)supplementary motor area and superior frontal gyrus. These findings provide evidence for damage to frontal-subcortical projections in TBI, which is associated with task switching impairments.

  11. MOS integrated circuit fault modeling

    NASA Technical Reports Server (NTRS)

    Sievers, M.

    1985-01-01

    Three digital simulation techniques for MOS integrated circuit faults were examined. These techniques embody a hierarchy of complexity bracketing the range of simulation levels. The digital approaches are: transistor-level, connector-switch-attenuator level, and gate level. The advantages and disadvantages are discussed. Failure characteristics are also described.

  12. Mobile Technology Integrated Pedagogical Model

    ERIC Educational Resources Information Center

    Khan, Arshia

    2014-01-01

    Integrated curricula and experiential learning are the main ingredients to the recipe to improve student learning in higher education. In the academic computer science world it is mostly assumed that this experiential learning takes place at a business as an internship experience. The intent of this paper is to schism the traditional understanding…

  13. Volumetric Intraoperative Brain Deformation Compensation: Model Development and Phantom Validation

    PubMed Central

    DeLorenzo, Christine; Papademetris, Xenophon; Staib, Lawrence H.; Vives, Kenneth P.; Spencer, Dennis D.; Duncan, James S.

    2012-01-01

    During neurosurgery, nonrigid brain deformation may affect the reliability of tissue localization based on preoperative images. To provide accurate surgical guidance in these cases, preoperative images must be updated to reflect the intraoperative brain. This can be accomplished by warping these preoperative images using a biomechanical model. Due to the possible complexity of this deformation, intraoperative information is often required to guide the model solution. In this paper, a linear elastic model of the brain is developed to infer volumetric brain deformation associated with measured intraoperative cortical surface displacement. The developed model relies on known material properties of brain tissue, and does not require further knowledge about intraoperative conditions. To provide an initial estimation of volumetric model accuracy, as well as determine the model’s sensitivity to the specified material parameters and surface displacements, a realistic brain phantom was developed. Phantom results indicate that the linear elastic model significantly reduced localization error due to brain shift, from >16 mm to under 5 mm, on average. In addition, though in vivo quantitative validation is necessary, preliminary application of this approach to images acquired during neocortical epilepsy cases confirms the feasibility of applying the developed model to in vivo data. PMID:22562728

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

    PubMed

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

    2014-01-01

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

  15. Reptiles: a new model for brain evo-devo research.

    PubMed

    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.

  16. Zebrafish as an emerging model for studying complex brain disorders

    PubMed Central

    Kalueff, Allan V.; Stewart, Adam Michael; Gerlai, Robert

    2014-01-01

    The zebrafish (Danio rerio) is rapidly becoming a popular model organism in pharmacogenetics and neuropharmacology. Both larval and adult zebrafish are currently used to increase our understanding of brain function, dysfunction, and their genetic and pharmacological modulation. Here we review the developing utility of zebrafish in the analysis of complex brain disorders (including, for example, depression, autism, psychoses, drug abuse and cognitive disorders), also covering zebrafish applications towards the goal of modeling major human neuropsychiatric and drug-induced syndromes. We argue that zebrafish models of complex brain disorders and drug-induced conditions have become a rapidly emerging critical field in translational neuropharmacology research. PMID:24412421

  17. Integrative modeling of the cardiac ventricular myocyte

    PubMed Central

    Winslow, Raimond L.; Cortassa, Sonia; O'Rourke, Brian; Hashambhoy, Yasmin L.; Rice, John Jeremy; Greenstein, Joseph L.

    2011-01-01

    Cardiac electrophysiology is a discipline with a rich 50-year history of experimental research coupled with integrative modeling which has enabled us to achieve a quantitative understanding of the relationships between molecular function and the integrated behavior of the cardiac myocyte in health and disease. In this paper, we review the development of integrative computational models of the cardiac myocyte. We begin with a historical overview of key cardiac cell models that helped shape the field. We then narrow our focus to models of the cardiac ventricular myocyte and describe these models in the context of their subcellular functional systems including dynamic models of voltage-gated ion channels, mitochondrial energy production, ATP-dependent and electrogenic membrane transporters, intracellular Ca dynamics, mechanical contraction, and regulatory signal transduction pathways. We describe key advances and limitations of the models as well as point to new directions for future modeling research. PMID:20865780

  18. Performance modeling of a wearable brain PET (BET) camera

    NASA Astrophysics Data System (ADS)

    Schmidtlein, C. R.; Turner, J. N.; Thompson, M. O.; Mandal, K. C.; Häggström, I.; Zhang, J.; Humm, J. L.; Feiglin, D. H.; Krol, A.

    2016-03-01

    Purpose: To explore, by means of analytical and Monte Carlo modeling, performance of a novel lightweight and low-cost wearable helmet-shaped Brain PET (BET) camera based on thin-film digital Geiger Avalanche Photo Diode (dGAPD) with LSO and LaBr3 scintillators for imaging in vivo human brain processes for freely moving and acting subjects responding to various stimuli in any environment. Methods: We performed analytical and Monte Carlo modeling PET performance of a spherical cap BET device and cylindrical brain PET (CYL) device, both with 25 cm diameter and the same total mass of LSO scintillator. Total mass of LSO in both the BET and CYL systems is about 32 kg for a 25 mm thick scintillator, and 13 kg for 10 mm thick scintillator (assuming an LSO density of 7.3 g/ml). We also investigated a similar system using an LaBr3 scintillator corresponding to 22 kg and 9 kg for the 25 mm and 10 mm thick systems (assuming an LaBr3 density of 5.08 g/ml). In addition, we considered a clinical whole body (WB) LSO PET/CT scanner with 82 cm ring diameter and 15.8 cm axial length to represent a reference system. BET consisted of distributed Autonomous Detector Arrays (ADAs) integrated into Intelligent Autonomous Detector Blocks (IADBs). The ADA comprised of an array of small LYSO scintillator volumes (voxels with base a×a: 1.0 <= a <= 2.0 mm and length c: 3.0 <= c <= 6.0 mm) with 5-65 μm thick reflective layers on its five sides and sixth side optically coupled to the matching array of dGAPDs and processing electronics with total thickness of 50 μm. Simulated energy resolution was 10.8% and 3.3% for LSO and LaBr3 respectively and the coincidence window was set at 2 ns. The brain was simulated as a sphere of uniform F-18 activity with diameter of 10 cm embedded in a center of water sphere with diameter of 10 cm. Results: Analytical and Monte Carlo models showed similar results for lower energy window values (458 keV versus 445 keV for LSO, and 492 keV versus 485 keV for LaBr3

  19. Delta Shell: Integrated Modeling by Example

    NASA Astrophysics Data System (ADS)

    Donchyts, G.; Jagers, B.; Baart, F.; Geer, P. V.

    2011-12-01

    We present the integrated modeling environment Delta Shell. It supports the full workflow of integrated environmental modeling: setup, configuration, simulation, analysis and reporting of results. Many components of the environment can be reused independently, allowing development of scientific, geospatial and other applications focused on data analysis, editing, visualization and storage. One of the unique features is that the Delta Shell environment integrates models from many different fields, such as hydrodynamics, hydrology, morphology, ecology, water quality, geospatial and decision support systems. This integration is possible due to flexible general data types, lightweight model coupling framework, the plugin system and the inclusion of a number of high quality open source components. Here we will use the open source morphological model XBeach as an example showing how to integrate models into the Delta Shell environment. Integration of XBeach adds a graphical interface which can be used to make testing coastal safety for complicated coastal areas easier. By using this example, we give an overview of the modeling framework and its possibilities. To increase the usability, the model is integrated with a coastal profile data set covering the whole coast of the Netherlands. This gives the end user a system to easily use the model for scanning the safety of the Dutch coast. The reuse of the components of the environment individually or combined is encouraged. They are available as separate components and have minimal or no dependencies on other components. This includes libraries to work with scientific multidimensional data, geospatial data (in particular geospatial coverages: values of some quantities defined on a spatial domain), editors, visualisation of time-dependent data and the modeling framework (projects, data linking, workflow management, model integration). Most components and the XBeach example are available as open source.

  20. Functional Integration of Adult-Born Hippocampal Neurons after Traumatic Brain Injury

    PubMed Central

    Villasana, Laura E.; Kim, Kristine N.

    2015-01-01

    Abstract Traumatic brain injury (TBI) increases hippocampal neurogenesis, which may contribute to cognitive recovery after injury. However, it is unknown whether TBI-induced adult-born neurons mature normally and functionally integrate into the hippocampal network. We assessed the generation, morphology, and synaptic integration of new hippocampal neurons after a controlled cortical impact (CCI) injury model of TBI. To label TBI-induced newborn neurons, we used 2-month-old POMC-EGFP mice, which transiently and specifically express EGFP in immature hippocampal neurons, and doublecortin-CreERT2 transgenic mice crossed with Rosa26-CAG-tdTomato reporter mice, to permanently pulse-label a cohort of adult-born hippocampal neurons. TBI increased the generation, outward migration, and dendritic complexity of neurons born during post-traumatic neurogenesis. Cells born after TBI had profound alterations in their dendritic structure, with increased dendritic branching proximal to the soma and widely splayed dendritic branches. These changes were apparent during early dendritic outgrowth and persisted as these cells matured. Whole-cell recordings from neurons generated during post-traumatic neurogenesis demonstrate that they are excitable and functionally integrate into the hippocampal circuit. However, despite their dramatic morphologic abnormalities, we found no differences in the rate of their electrophysiological maturation, or their overall degree of synaptic integration when compared to age-matched adult-born cells from sham mice. Our results suggest that cells born after TBI participate in information processing, and receive an apparently normal balance of excitatory and inhibitory inputs. However, TBI-induced changes in their anatomic localization and dendritic projection patterns could result in maladaptive network properties. PMID:26478908

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

    PubMed

    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.

  2. Allen Brain Atlas: an integrated spatio-temporal portal for exploring the central nervous system

    PubMed Central

    Sunkin, Susan M.; Ng, Lydia; Lau, Chris; Dolbeare, Tim; Gilbert, Terri L.; Thompson, Carol L.; Hawrylycz, Michael; Dang, Chinh

    2013-01-01

    The Allen Brain Atlas (http://www.brain-map.org) provides a unique online public resource integrating extensive gene expression data, connectivity data and neuroanatomical information with powerful search and viewing tools for the adult and developing brain in mouse, human and non-human primate. Here, we review the resources available at the Allen Brain Atlas, describing each product and data type [such as in situ hybridization (ISH) and supporting histology, microarray, RNA sequencing, reference atlases, projection mapping and magnetic resonance imaging]. In addition, standardized and unique features in the web applications are described that enable users to search and mine the various data sets. Features include both simple and sophisticated methods for gene searches, colorimetric and fluorescent ISH image viewers, graphical displays of ISH, microarray and RNA sequencing data, Brain Explorer software for 3D navigation of anatomy and gene expression, and an interactive reference atlas viewer. In addition, cross data set searches enable users to query multiple Allen Brain Atlas data sets simultaneously. All of the Allen Brain Atlas resources can be accessed through the Allen Brain Atlas data portal. PMID:23193282

  3. Allen Brain Atlas: an integrated spatio-temporal portal for exploring the central nervous system.

    PubMed

    Sunkin, Susan M; Ng, Lydia; Lau, Chris; Dolbeare, Tim; Gilbert, Terri L; Thompson, Carol L; Hawrylycz, Michael; Dang, Chinh

    2013-01-01

    The Allen Brain Atlas (http://www.brain-map.org) provides a unique online public resource integrating extensive gene expression data, connectivity data and neuroanatomical information with powerful search and viewing tools for the adult and developing brain in mouse, human and non-human primate. Here, we review the resources available at the Allen Brain Atlas, describing each product and data type [such as in situ hybridization (ISH) and supporting histology, microarray, RNA sequencing, reference atlases, projection mapping and magnetic resonance imaging]. In addition, standardized and unique features in the web applications are described that enable users to search and mine the various data sets. Features include both simple and sophisticated methods for gene searches, colorimetric and fluorescent ISH image viewers, graphical displays of ISH, microarray and RNA sequencing data, Brain Explorer software for 3D navigation of anatomy and gene expression, and an interactive reference atlas viewer. In addition, cross data set searches enable users to query multiple Allen Brain Atlas data sets simultaneously. All of the Allen Brain Atlas resources can be accessed through the Allen Brain Atlas data portal.

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

    NASA Astrophysics Data System (ADS)

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

    2016-03-01

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

  5. Integrating language models into classifiers for BCI communication: a review

    NASA Astrophysics Data System (ADS)

    Speier, W.; Arnold, C.; Pouratian, N.

    2016-06-01

    Objective. The present review systematically examines the integration of language models to improve classifier performance in brain-computer interface (BCI) communication systems. Approach. The domain of natural language has been studied extensively in linguistics and has been used in the natural language processing field in applications including information extraction, machine translation, and speech recognition. While these methods have been used for years in traditional augmentative and assistive communication devices, information about the output domain has largely been ignored in BCI communication systems. Over the last few years, BCI communication systems have started to leverage this information through the inclusion of language models. Main results. Although this movement began only recently, studies have already shown the potential of language integration in BCI communication and it has become a growing field in BCI research. BCI communication systems using language models in their classifiers have progressed down several parallel paths, including: word completion; signal classification; integration of process models; dynamic stopping; unsupervised learning; error correction; and evaluation. Significance. Each of these methods have shown significant progress, but have largely been addressed separately. Combining these methods could use the full potential of language model, yielding further performance improvements. This integration should be a priority as the field works to create a BCI system that meets the needs of the amyotrophic lateral sclerosis population.

  6. Optically enhanced blood-brain-barrier crossing of plasmonic-active nanoparticles in preclinical brain tumor animal models

    NASA Astrophysics Data System (ADS)

    Yuan, Hsiangkuo; Wilson, Christy M.; Li, Shuqin; Fales, Andrew M.; Liu, Yang; Grant, Gerald; Vo-Dinh, Tuan

    2014-02-01

    Nanotechnology provides tremendous biomedical opportunities for cancer diagnosis, imaging, and therapy. In contrast to conventional chemotherapeutic agents where their actual target delivery cannot be easily imaged, integrating imaging and therapeutic properties into one platform facilitates the understanding of pharmacokinetic profiles, and enables monitoring of the therapeutic process in each individual. Such a concept dubbed "theranostics" potentiates translational research and improves precision medicine. One particular challenging application of theranostics involves imaging and controlled delivery of nanoplatforms across blood-brain-barrier (BBB) into brain tissues. Typically, the BBB hinders paracellular flux of drug molecules into brain parenchyma. BBB disrupting agents (e.g. mannitol, focused ultrasound), however, suffer from poor spatial confinement. It has been a challenge to design a nanoplatform not only acts as a contrast agent but also improves the BBB permeation. In this study, we demonstrated the feasibility of plasmonic gold nanoparticles as both high-resolution optical contrast agent and focalized tumor BBB permeation-inducing agent. We specifically examined the microscopic distribution of nanoparticles in tumor brain animal models. We observed that most nanoparticles accumulated at the tumor periphery or perivascular spaces. Nanoparticles were present in both endothelial cells and interstitial matrices. This study also demonstrated a novel photothermal-induced BBB permeation. Fine-tuning the irradiating energy induced gentle disruption of the vascular integrity, causing short-term extravasation of nanomaterials but without hemorrhage. We conclude that our gold nanoparticles are a powerful biocompatible contrast agent capable of inducing focal BBB permeation, and therefore envision a strong potential of plasmonic gold nanoparticle in future brain tumor imaging and therapy.

  7. Controlling ferrofluid permeability across the blood–brain barrier model.

    PubMed

    Shi, Di; Sun, Linlin; Mi, Gujie; Sheikh, Lubna; Bhattacharya, Soumya; Nayar, Suprabha; Webster, Thomas J

    2014-02-21

    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 FITCDextran 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).

  8. Controlling ferrofluid permeability across the blood-brain barrier model

    NASA Astrophysics Data System (ADS)

    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).

  9. From hippocampus to whole-brain: The role of integrative processing in episodic memory retrieval.

    PubMed

    Geib, Benjamin R; Stanley, Matthew L; Dennis, Nancy A; Woldorff, Marty G; Cabeza, Roberto

    2017-04-01

    Multivariate functional connectivity analyses of neuroimaging data have revealed the importance of complex, distributed interactions between disparate yet interdependent brain regions. Recent work has shown that topological properties of functional brain networks are associated with individual and group differences in cognitive performance, including in episodic memory. After constructing functional whole-brain networks derived from an event-related fMRI study of memory retrieval, we examined differences in functional brain network architecture between forgotten and remembered words. This study yielded three main findings. First, graph theory analyses showed that successfully remembering compared to forgetting was associated with significant changes in the connectivity profile of the left hippocampus and a corresponding increase in efficient communication with the rest of the brain. Second, bivariate functional connectivity analyses indicated stronger interactions between the left hippocampus and a retrieval assembly for remembered versus forgotten items. This assembly included the left precuneus, left caudate, bilateral supramarginal gyrus, and the bilateral dorsolateral superior frontal gyrus. Integrative properties of the retrieval assembly were greater for remembered than forgotten items. Third, whole-brain modularity analyses revealed that successful memory retrieval was marginally significantly associated with a less segregated modular architecture in the network. The magnitude of the decreases in modularity between remembered and forgotten conditions was related to memory performance. These findings indicate that increases in integrative properties at the nodal, retrieval assembly, and whole-brain topological levels facilitate memory retrieval, while also underscoring the potential of multivariate brain connectivity approaches for providing valuable new insights into the neural bases of memory processes. Hum Brain Mapp 38:2242-2259, 2017. © 2017 Wiley

  10. Social Outcomes in Childhood Brain Disorder: A Heuristic Integration of Social Neuroscience and Developmental Psychology

    PubMed Central

    Yeates, Keith Owen; Bigler, Erin D.; Dennis, Maureen; Gerhardt, Cynthia A.; Rubin, Kenneth H.; Stancin, Terry; Taylor, H. Gerry; Vannatta, Kathryn

    2010-01-01

    The authors propose a heuristic model of the social outcomes of childhood brain disorder that draws on models and methods from both the emerging field of social cognitive neuroscience and the study of social competence in developmental psychology/psychopathology. The heuristic model characterizes the relationships between social adjustment, peer interactions and relationships, social problem solving and communication, social-affective and cognitive-executive processes, and their neural substrates. The model is illustrated by research on a specific form of childhood brain disorder, traumatic brain injury. The heuristic model may promote research regarding the neural and cognitive-affective substrates of children’s social development. It also may engender more precise methods of measuring impairments and disabilities in children with brain disorder and suggest ways to promote their social adaptation. PMID:17469991

  11. Social Ecological Model Analysis for ICT Integration

    ERIC Educational Resources Information Center

    Zagami, Jason

    2013-01-01

    ICT integration of teacher preparation programmes was undertaken by the Australian Teaching Teachers for the Future (TTF) project in all 39 Australian teacher education institutions and highlighted the need for guidelines to inform systemic ICT integration approaches. A Social Ecological Model (SEM) was used to positively inform integration…

  12. An integrated communications demand model

    NASA Astrophysics Data System (ADS)

    Doubleday, C. F.

    1980-11-01

    A computer model of communications demand is being developed to permit dynamic simulations of the long-term evolution of demand for communications media in the U.K. to be made under alternative assumptions about social, economic and technological trends in British Telecom's business environment. The context and objectives of the project and the potential uses of the model are reviewed, and four key concepts in the demand for communications media, around which the model is being structured are discussed: (1) the generation of communications demand; (2) substitution between media; (3) technological convergence; and (4) competition. Two outline perspectives on the model itself are given.

  13. Gpr124 is essential for blood-brain barrier integrity in central nervous system disease.

    PubMed

    Chang, Junlei; Mancuso, Michael R; Maier, Carolina; Liang, Xibin; Yuki, Kanako; Yang, Lu; Kwong, Jeffrey W; Wang, Jing; Rao, Varsha; Vallon, Mario; Kosinski, Cynthia; Zhang, J J Haijing; Mah, Amanda T; Xu, Lijun; Li, Le; Gholamin, Sharareh; Reyes, Teresa F; Li, Rui; Kuhnert, Frank; Han, Xiaoyuan; Yuan, Jenny; Chiou, Shin-Heng; Brettman, Ari D; Daly, Lauren; Corney, David C; Cheshier, Samuel H; Shortliffe, Linda D; Wu, Xiwei; Snyder, Michael; Chan, Pak; Giffard, Rona G; Chang, Howard Y; Andreasson, Katrin; Kuo, Calvin J

    2017-04-01

    Although blood-brain barrier (BBB) compromise is central to the etiology of diverse central nervous system (CNS) disorders, endothelial receptor proteins that control BBB function are poorly defined. The endothelial G-protein-coupled receptor (GPCR) Gpr124 has been reported to be required for normal forebrain angiogenesis and BBB function in mouse embryos, but the role of this receptor in adult animals is unknown. Here Gpr124 conditional knockout (CKO) in the endothelia of adult mice did not affect homeostatic BBB integrity, but resulted in BBB disruption and microvascular hemorrhage in mouse models of both ischemic stroke and glioblastoma, accompanied by reduced cerebrovascular canonical Wnt-β-catenin signaling. Constitutive activation of Wnt-β-catenin signaling fully corrected the BBB disruption and hemorrhage defects of Gpr124-CKO mice, with rescue of the endothelial gene tight junction, pericyte coverage and extracellular-matrix deficits. We thus identify Gpr124 as an endothelial GPCR specifically required for endothelial Wnt signaling and BBB integrity under pathological conditions in adult mice. This finding implicates Gpr124 as a potential therapeutic target for human CNS disorders characterized by BBB disruption.

  14. A propositional representation model of anatomical and functional brain data.

    PubMed

    Maturana, Pablo; Batrancourt, Bénédicte

    2011-01-01

    Networks can represent a large number of systems. Recent advances in the domain of networks have been transferred to the field of neuroscience. For example, the graph model has been used in neuroscience research as a methodological tool to examine brain networks organization, topology and complex dynamics, as well as a framework to test the structure-function hypothesis using neuroimaging data. In the current work we propose a graph-theoretical framework to represent anatomical, functional and neuropsychological assessment instruments information. On the one hand, interrelationships between anatomic elements constitute an anatomical graph. On the other hand, a functional graph contains several cognitive functions and their more elementary cognitive processes. Finally, the neuropsychological assessment instruments graph includes several neuropsychological tests and scales linked with their different sub-tests and variables. The two last graphs are connected by relations of type "explore" linking a particular instrument with the cognitive function it explores. We applied this framework to a sample of patients with focal brain damage. Each patient was related to: (i) the cerebral entities injured (assessed with structural neuroimaging data) and (ii) the neusopsychological assessment tests carried out (weight by performance). Our model offers a suitable platform to visualize patients' relevant information, facilitating the representation, standardization and sharing of clinical data. At the same time, the integration of a large number of patients in this framework will make possible to explore relations between anatomy (injured entities) and function (performance in different tests assessing different cognitive functions) and the use of neurocomputational tools for graph analysis may help diagnostic and contribute to the comprehension of neural bases of cognitive functions.

  15. GABA regulates synaptic integration of newly generated neurons in the adult brain

    NASA Astrophysics Data System (ADS)

    Ge, Shaoyu; Goh, Eyleen L. K.; Sailor, Kurt A.; Kitabatake, Yasuji; Ming, Guo-Li; Song, Hongjun

    2006-02-01

    Adult neurogenesis, the birth and integration of new neurons from adult neural stem cells, is a striking form of structural plasticity and highlights the regenerative capacity of the adult mammalian brain. Accumulating evidence suggests that neuronal activity regulates adult neurogenesis and that new neurons contribute to specific brain functions. The mechanism that regulates the integration of newly generated neurons into the pre-existing functional circuitry in the adult brain is unknown. Here we show that newborn granule cells in the dentate gyrus of the adult hippocampus are tonically activated by ambient GABA (γ-aminobutyric acid) before being sequentially innervated by GABA- and glutamate-mediated synaptic inputs. GABA, the major inhibitory neurotransmitter in the adult brain, initially exerts an excitatory action on newborn neurons owing to their high cytoplasmic chloride ion content. Conversion of GABA-induced depolarization (excitation) into hyperpolarization (inhibition) in newborn neurons leads to marked defects in their synapse formation and dendritic development in vivo. Our study identifies an essential role for GABA in the synaptic integration of newly generated neurons in the adult brain, and suggests an unexpected mechanism for activity-dependent regulation of adult neurogenesis, in which newborn neurons may sense neuronal network activity through tonic and phasic GABA activation.

  16. Integrated Environmental Modeling: Quantitative Microbial Risk Assessment

    EPA Science Inventory

    The presentation discusses the need for microbial assessments and presents a road map associated with quantitative microbial risk assessments, through an integrated environmental modeling approach. A brief introduction and the strengths of the current knowledge are illustrated. W...

  17. A Novel Three-Phase Model of Brain Tissue Microstructure

    PubMed Central

    Gevertz, Jana L.; Torquato, Salvatore

    2008-01-01

    We propose a novel biologically constrained three-phase model of the brain microstructure. Designing a realistic model is tantamount to a packing problem, and for this reason, a number of techniques from the theory of random heterogeneous materials can be brought to bear on this problem. Our analysis strongly suggests that previously developed two-phase models in which cells are packed in the extracellular space are insufficient representations of the brain microstructure. These models either do not preserve realistic geometric and topological features of brain tissue or preserve these properties while overestimating the brain's effective diffusivity, an average measure of the underlying microstructure. In light of the highly connected nature of three-dimensional space, which limits the minimum diffusivity of biologically constrained two-phase models, we explore the previously proposed hypothesis that the extracellular matrix is an important factor that contributes to the diffusivity of brain tissue. Using accurate first-passage-time techniques, we support this hypothesis by showing that the incorporation of the extracellular matrix as the third phase of a biologically constrained model gives the reduction in the diffusion coefficient necessary for the three-phase model to be a valid representation of the brain microstructure. PMID:18704170

  18. Microcounselling Supervision: An Innovative Integrated Supervision Model

    ERIC Educational Resources Information Center

    Russell-Chapin, Lori A.; Ivey, Allen E.

    2004-01-01

    This article introduces a new integrated model of counselling supervision entitled the Microcounselling Supervision Model (MSM). This type of supervision is designed for supervisors and supervisees who favor eclecticism and work from multiple theoretical orientations. MSM successfully combines skills from various theories and supervision models by…

  19. Brain Penetration and Efficacy of Different Mebendazole Polymorphs in a Mouse Brain Tumor Model

    PubMed Central

    Wanjiku, Teresia; Rudek, Michelle A; Joshi, Avadhut; Gallia, Gary L.; Riggins, Gregory J.

    2015-01-01

    Purpose Mebendazole (MBZ), first used as an antiparasitic drug, shows preclinical efficacy in models of glioblastoma and medulloblastoma. Three different MBZ polymorphs (A, B and C) exist and a detailed assessment of the brain penetration, pharmacokinetics and anti-tumor properties of each individual MBZ polymorph is necessary to improve mebendazole-based brain cancer therapy. Experimental Design and Results In this study, various marketed and custom-formulated MBZ tablets were analyzed for their polymorph content by IR spectroscopy and subsequently tested in orthotopic GL261 mouse glioma model for efficacy and tolerability. The pharmacokinetics and brain concentration of MBZ polymorphs and two main metabolites were analyzed by LC-MS. We found that polymorph B and C both increased survival in a GL261 glioma model, as B exhibited greater toxicity. Polymorph A showed no benefit. Both, polymorph B and C, reached concentrations in the brain that exceeded the IC50 in GL261 cells 29-fold. In addition, polymorph C demonstrated an AUC0-24h brain-to-plasma (B/P) ratio of 0.82, whereas B showed higher plasma AUC and lower B/P ratio. In contrast, polymorph A presented markedly lower levels in the plasma and brain. Furthermore, the combination with elacridar was able to significantly improve the efficacy of polymorph C in GL261 glioma and D425 medulloblastoma models in mice. Conclusion Among MBZ polymorphs, C reaches therapeutically effective concentrations in the brain tissue and tumor with less side effects and is the better choice for brain cancer therapy. Its efficacy can be further enhanced by combination with elacridar. PMID:25862759

  20. [Evaluation of the community integration of persons with lateralised post-acute acquired brain injury].

    PubMed

    Huertas-Hoyas, E; Pedrero-Perez, E J; Aguila-Maturana, A M; Gonzalez-Alted, C

    2013-08-16

    INTRODUCTION. Hemispheric specialization is a topic of interest that has motivated an enormous amount of research in recent decades. After a unilateral brain injury, the consequences can affect various areas of specialization, leading, depending on the location of the injury, impairment in quality of life and community integration. PATIENTS AND METHODS. Cross-sectional study with a sample of 58 patients, 28 traumatic brain injury (TBI) and 30 cerebrovascular accidents, both lateralized. The level of integration in the community is measured by the Community Integration Questionnaire. RESULTS. There were three groups analyzed by considering unilateral injury (full sample, stroke sample, and TBI sample). Results showed a significantly high community integration of people with right hemisphere injury. However, to measure the level of community integration between TBI and stroke, the results showed no significant differences. CONCLUSION. According to the results of the study people with brain injury in the right hemisphere have a better community integration than people with lesions in the left hemisphere regardless of the origin of the lesions (vascular or traumatic). We discussed the reasons that may motivate the differences and clinical implications.

  1. Development of a model for whole brain learning of physiology.

    PubMed

    Eagleton, Saramarie; Muller, Anton

    2011-12-01

    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 elaborates on these layers by relating the personality traits central to learning to the different quadrants of brain preference, as described by Neethling's brain profile, as the inner layer of the onion. This layer is encircled by the learning styles that describe different information-processing preferences for each brain quadrant. For the middle layer, the different stages of Kolb's learning cycle are classified into the four brain quadrants associated with the different brain processing strategies within the information processing circle. Each of the stages of Kolb's learning cycle is also associated with a specific cognitive learning strategy. These two inner circles are enclosed by the circle representing the role of the environment and instruction on learning. It relates environmental factors that affect learning and distinguishes between face-to-face and technology-assisted learning. This model informs on the design of instructional interventions for physiology to encourage whole brain learning.

  2. Integrating Whole Brain Teaching Strategies to Create a More Engaged Learning Environment

    ERIC Educational Resources Information Center

    Palasigue, Jesame Torres

    2009-01-01

    In today's postmodern society, it is getting harder and harder to get the students engaged in classroom instruction and learning. The purpose of this research project was to seek ways to create a more engaged learning environment for the students. The teacher-researcher integrated the most current educational reform "Whole Brain Teaching" method…

  3. Brain tumor modeling: glioma growth and interaction with chemotherapy

    NASA Astrophysics Data System (ADS)

    Banaem, Hossein Y.; Ahmadian, Alireza; Saberi, Hooshangh; Daneshmehr, Alireza; Khodadad, Davood

    2011-10-01

    In last decade increasingly mathematical models of tumor growths have been studied, particularly on solid tumors which growth mainly caused by cellular proliferation. In this paper we propose a modified model to simulate the growth of gliomas in different stages. Glioma growth is modeled by a reaction-advection-diffusion. We begin with a model of untreated gliomas and continue with models of polyclonal glioma following chemotherapy. From relatively simple assumptions involving homogeneous brain tissue bounded by a few gross anatomical landmarks (ventricles and skull) the models have been expanded to include heterogeneous brain tissue with different motilities of glioma cells in grey and white matter. Tumor growth is characterized by a dangerous change in the control mechanisms, which normally maintain a balance between the rate of proliferation and the rate of apoptosis (controlled cell death). Result shows that this model closes to clinical finding and can simulate brain tumor behavior properly.

  4. Preservation of mitochondrial functional integrity in mitochondria isolated from small cryopreserved mouse brain areas.

    PubMed

    Valenti, Daniela; de Bari, Lidia; De Filippis, Bianca; Ricceri, Laura; Vacca, Rosa Anna

    2014-01-01

    Studies of mitochondrial bioenergetics in brain pathophysiology are often precluded by the need to isolate mitochondria immediately after tissue dissection from a large number of brain biopsies for comparative studies. Here we present a procedure of cryopreservation of small brain areas from which mitochondrial enriched fractions (crude mitochondria) with high oxidative phosphorylation efficiency can be isolated. Small mouse brain areas were frozen and stored in a solution containing glycerol as cryoprotectant. Crude mitochondria were isolated by differential centrifugation from both cryopreserved and freshly explanted brain samples and were compared with respect to their ability to generate membrane potential and produce ATP. Intactness of outer and inner mitochondrial membranes was verified by polarographic ascorbate and cytochrome c tests and spectrophotometric assay of citrate synthase activity. Preservation of structural integrity and oxidative phosphorylation efficiency was successfully obtained in crude mitochondria isolated from different areas of cryopreserved mouse brain samples. Long-term cryopreservation of small brain areas from which intact and phosphorylating mitochondria can be isolated for the study of mitochondrial bioenergetics will significantly expand the study of mitochondrial defects in neurological pathologies, allowing large comparative studies and favoring interlaboratory and interdisciplinary analyses.

  5. Finite element modeling of human brain response to football helmet impacts.

    PubMed

    Darling, T; Muthuswamy, J; Rajan, S D

    2016-10-01

    The football helmet is used to help mitigate the occurrence of impact-related traumatic (TBI) and minor traumatic brain injuries (mTBI) in the game of American football. While the current helmet design methodology may be adequate for reducing linear acceleration of the head and minimizing TBI, it however has had less effect in minimizing mTBI. The objectives of this study are (a) to develop and validate a coupled finite element (FE) model of a football helmet and the human body, and (b) to assess responses of different regions of the brain to two different impact conditions - frontal oblique and crown impact conditions. The FE helmet model was validated using experimental results of drop tests. Subsequently, the integrated helmet-human body FE model was used to assess the responses of different regions of the brain to impact loads. Strain-rate, strain, and stress measures in the corpus callosum, midbrain, and brain stem were assessed. Results show that maximum strain-rates of 27 and 19 s(-1) are observed in the brain-stem and mid-brain, respectively. This could potentially lead to axonal injuries and neuronal cell death during crown impact conditions. The developed experimental-numerical framework can be used in the study of other helmet-related impact conditions.

  6. Inflammation regulates functional integration of neurons born in adult brain.

    PubMed

    Jakubs, Katherine; Bonde, Sara; Iosif, Robert E; Ekdahl, Christine T; Kokaia, Zaal; Kokaia, Merab; Lindvall, Olle

    2008-11-19

    Inflammation influences several steps of adult neurogenesis, but whether it regulates the functional integration of the new neurons is unknown. Here, we explored, using confocal microscopy and whole-cell patch-clamp recordings, whether a chronic inflammatory environment affects the morphological and electrophysiological properties of new dentate gyrus granule cells, labeled with a retroviral vector encoding green fluorescent protein. Rats were exposed to intrahippocampal injection of lipopolysaccharide, which gave rise to long-lasting microglia activation. Inflammation caused no changes in intrinsic membrane properties, location, dendritic arborization, or spine density and morphology of the new cells. Excitatory synaptic drive increased to the same extent in new and mature cells in the inflammatory environment, suggesting increased network activity in hippocampal neural circuitries of lipopolysaccharide-treated animals. In contrast, inhibitory synaptic drive was more enhanced by inflammation in the new cells. Also, larger clusters of the postsynaptic GABA(A) receptor scaffolding protein gephyrin were found on dendrites of new cells born in the inflammatory environment. We demonstrate for the first time that inflammation influences the functional integration of adult-born hippocampal neurons. Our data indicate a high degree of synaptic plasticity of the new neurons in the inflammatory environment, which enables them to respond to the increase in excitatory input with a compensatory upregulation of activity and efficacy at their afferent inhibitory synapses.

  7. A planning study of simultaneous integrated boost with forward IMRT for multiple brain metastases

    SciTech Connect

    Liang, Xiaodong; Ni, Lingqin; Hu, Wei; Chen, Weijun; Ying, Shenpeng; Gong, Qiangjun; Liu, Yanmei

    2013-07-01

    The objective of this study was to evaluate the dose conformity and feasibility of whole-brain radiotherapy with a simultaneous integrated boost by forward intensity-modulated radiation therapy in patients with 1 to 3 brain metastases. Forward intensity-modulated radiation therapy plans were generated for 10 patients with 1 to 3 brain metastases on Pinnacle 6.2 Treatment Planning System. The prescribed dose was 30 Gy to the whole brain (planning target volume [PTV]{sub wbrt}) and 40 Gy to individual brain metastases (PTV{sub boost}) simultaneously, and both doses were given in 10 fractions. The maximum diameters of individual brain metastases ranged from 1.6 to 6 cm, and the summated PTVs per patient ranged from 1.62 to 69.81 cm{sup 3}. Conformity and feasibility were evaluated regarding conformation number and treatment delivery time. One hundred percent volume of the PTV{sub boost} received at least 95% of the prescribed dose in all cases. The maximum doses were less than 110% of the prescribed dose to the PTV{sub boost}, and all of the hot spots were within the PTV{sub boost}. The volume of the PTV{sub wbrt} that received at least 95% of the prescribed dose ranged from 99.2% to 100%. The mean values of conformation number were 0.682. The mean treatment delivery time was 2.79 minutes. Ten beams were used on an average in these plans. Whole-brain radiotherapy with a simultaneous integrated boost by forward intensity-modulated radiation therapy in 1 to 3 brain metastases is feasible, and treatment delivery time is short.

  8. The definition of community integration: perspectives of people with brain injuries.

    PubMed

    McColl, M A; Carlson, P; Johnston, J; Minnes, P; Shue, K; Davies, D; Karlovits, T

    1998-01-01

    Despite considerable attention to community integration and related topics in the past decades, a clear definition of community integration continues to elude researchers and service providers. Common to most discussions of the topic, however, are three ideas: that integration involves relationships with others, independence in one's living situation and activities to fill one's time. The present study sought to expand this conceptualization of community integration by asking people with brain injuries for their own perspectives on community integration. This qualitative study resulted in a definition of community integration consisting of nine indicators: orientation, acceptance, conformity, close and diffuse relationships, living situation, independence, productivity and leisure. These indicators were empirically derived from the text of 116 interviews with people with moderate-severe brain injuries living in the community. Eighteen adults living in supported living programmes were followed for 1 year, to track their evolving definition of integration and the factors they felt were related to integration. The study also showed a general trend toward more positive evaluation over the year, and revealed that positive evaluation was frequently related to meeting new people and freedom from staff supervision. These findings are interpreted in the light of recommendations for community programmes.

  9. Alteration of Blood–Brain Barrier Integrity by Retroviral Infection

    PubMed Central

    Afonso, Philippe V.; Ozden, Simona; Cumont, Marie-Christine; Seilhean, Danielle; Cartier, Luis; Rezaie, Payam; Mason, Sarah; Lambert, Sophie; Huerre, Michel; Gessain, Antoine; Couraud, Pierre-Olivier; Pique, Claudine

    2008-01-01

    The blood–brain barrier (BBB), which forms the interface between the blood and the cerebral parenchyma, has been shown to be disrupted during retroviral-associated neuromyelopathies. Human T Lymphotropic Virus (HTLV-1) Associated Myelopathy/Tropical Spastic Paraparesis (HAM/TSP) is a slowly progressive neurodegenerative disease associated with BBB breakdown. The BBB is composed of three cell types: endothelial cells, pericytes and astrocytes. Although astrocytes have been shown to be infected by HTLV-1, until now, little was known about the susceptibility of BBB endothelial cells to HTLV-1 infection and the impact of such an infection on BBB function. We first demonstrated that human cerebral endothelial cells express the receptors for HTLV-1 (GLUT-1, Neuropilin-1 and heparan sulfate proteoglycans), both in vitro, in a human cerebral endothelial cell line, and ex vivo, on spinal cord autopsy sections from HAM/TSP and non-infected control cases. In situ hybridization revealed HTLV-1 transcripts associated with the vasculature in HAM/TSP. We were able to confirm that the endothelial cells could be productively infected in vitro by HTLV-1 and that blocking of either HSPGs, Neuropilin 1 or Glut1 inhibits this process. The expression of the tight-junction proteins within the HTLV-1 infected endothelial cells was altered. These cells were no longer able to form a functional barrier, since BBB permeability and lymphocyte passage through the monolayer of endothelial cells were increased. This work constitutes the first report of susceptibility of human cerebral endothelial cells to HTLV-1 infection, with implications for HTLV-1 passage through the BBB and subsequent deregulation of the central nervous system homeostasis. We propose that the susceptibility of cerebral endothelial cells to retroviral infection and subsequent BBB dysfunction is an important aspect of HAM/TSP pathogenesis and should be considered in the design of future therapeutics strategies. PMID:19008946

  10. Cerebral organoids model human brain development and microcephaly.

    PubMed

    Lancaster, Madeline A; Renner, Magdalena; Martin, Carol-Anne; Wenzel, Daniel; Bicknell, Louise S; Hurles, Matthew E; Homfray, Tessa; Penninger, Josef M; Jackson, Andrew P; Knoblich, Juergen A

    2013-09-19

    The complexity of the human brain has made it difficult to study many brain disorders in model organisms, highlighting the need for an in vitro model of human brain development. Here we have developed a human pluripotent stem cell-derived three-dimensional organoid culture system, termed cerebral organoids, that develop various discrete, although interdependent, brain regions. These include a cerebral cortex containing progenitor populations that organize and produce mature cortical neuron subtypes. Furthermore, cerebral organoids are shown to recapitulate features of human cortical development, namely characteristic progenitor zone organization with abundant outer radial glial stem cells. Finally, we use RNA interference and patient-specific induced pluripotent stem cells to model microcephaly, a disorder that has been difficult to recapitulate in mice. We demonstrate premature neuronal differentiation in patient organoids, a defect that could help to explain the disease phenotype. Together, these data show that three-dimensional organoids can recapitulate development and disease even in this most complex human tissue.

  11. Integrated dynamics modeling for supercavitating vehicle systems

    NASA Astrophysics Data System (ADS)

    Kim, Seonhong; Kim, Nakwan

    2015-06-01

    We have performed integrated dynamics modeling for a supercavitating vehicle. A 6-DOF equation of motion was constructed by defining the forces and moments acting on the supercavitating body surface that contacted water. The wetted area was obtained by calculating the cavity size and axis. Cavity dynamics were determined to obtain the cavity profile for calculating the wetted area. Subsequently, the forces and moments acting on each wetted part-the cavitator, fins, and vehicle body-were obtained by physical modeling. The planing force-the interaction force between the vehicle transom and cavity wall-was calculated using the apparent mass of the immersed vehicle transom. We integrated each model and constructed an equation of motion for the supercavitating system. We performed numerical simulations using the integrated dynamics model to analyze the characteristics of the supercavitating system and validate the modeling completeness. Our research enables the design of high-quality controllers and optimal supercavitating systems.

  12. The most relevant human brain regions for functional connectivity: Evidence for a dynamical workspace of binding nodes from whole-brain computational modelling.

    PubMed

    Deco, Gustavo; Van Hartevelt, Tim J; Fernandes, Henrique M; Stevner, Angus; Kringelbach, Morten L

    2017-02-01

    In order to promote survival through flexible cognition and goal-directed behaviour, the brain has to optimize segregation and integration of information into coherent, distributed dynamical states. Certain organizational features of the brain have been proposed to be essential to facilitate cognitive flexibility, especially hub regions in the so-called rich club which show dense interconnectivity. These structural hubs have been suggested to be vital for integration and segregation of information. Yet, this has not been evaluated in terms of resulting functional temporal dynamics. A complementary measure covering the temporal aspects of functional connectivity could thus bring new insights into a more complete picture of the integrative nature of brain networks. Here, we use causal whole-brain computational modelling to determine the functional dynamical significance of the rich club and compare this to a new measure of the most functionally relevant brain regions for binding information over time ("dynamical workspace of binding nodes"). We found that removal of the iteratively generated workspace of binding nodes impacts significantly more on measures of integration and encoding of information capability than the removal of the rich club regions. While the rich club procedure produced almost half of the binding nodes, the remaining nodes have low degree yet still play a significant role in the workspace essential for binding information over time and as such goes beyond a description of the structural backbone.

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

    PubMed Central

    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

  14. The Application of Integrated Knowledge-based Systems for the Biomedical Risk Assessment Intelligent Network (BRAIN)

    NASA Technical Reports Server (NTRS)

    Loftin, Karin C.; Ly, Bebe; Webster, Laurie; Verlander, James; Taylor, Gerald R.; Riley, Gary; Culbert, Chris; Holden, Tina; Rudisill, Marianne

    1993-01-01

    One of NASA's goals for long duration space flight is to maintain acceptable levels of crew health, safety, and performance. One way of meeting this goal is through the Biomedical Risk Assessment Intelligent Network (BRAIN), an integrated network of both human and computer elements. The BRAIN will function as an advisor to flight surgeons by assessing the risk of in-flight biomedical problems and recommending appropriate countermeasures. This paper describes the joint effort among various NASA elements to develop BRAIN and an Infectious Disease Risk Assessment (IDRA) prototype. The implementation of this effort addresses the technological aspects of the following: (1) knowledge acquisition; (2) integration of IDRA components; (3) use of expert systems to automate the biomedical prediction process; (4) development of a user-friendly interface; and (5) integration of the IDRA prototype and Exercise Countermeasures Intelligent System (ExerCISys). Because the C Language, CLIPS (the C Language Integrated Production System), and the X-Window System were portable and easily integrated, they were chosen as the tools for the initial IDRA prototype. The feasibility was tested by developing an IDRA prototype that predicts the individual risk of influenza. The application of knowledge-based systems to risk assessment is of great market value to the medical technology industry.

  15. Music plus Music Integration: A Model for Music Education Policy Reform That Reflects the Evolution and Success of Arts Integration Practices in 21st Century American Public Schools

    ERIC Educational Resources Information Center

    Scripp, Lawrence; Gilbert, Josh

    2016-01-01

    This article explores the special case of integrative teaching and learning in music as a model for 21st century music education policy reform based on the principles that have evolved out of arts integration research and practices over the past century and informed by the recent rising tide of evidence of music's impact on brain capacity and…

  16. Large-scale in silico modeling of metabolic interactions between cell types in the human brain.

    PubMed

    Lewis, Nathan E; Schramm, Gunnar; Bordbar, Aarash; Schellenberger, Jan; Andersen, Michael P; Cheng, Jeffrey K; Patel, Nilam; Yee, Alex; Lewis, Randall A; Eils, Roland; König, Rainer; Palsson, Bernhard Ø

    2010-12-01

    Metabolic interactions between multiple cell types are difficult to model using existing approaches. Here we present a workflow that integrates gene expression data, proteomics data and literature-based manual curation to model human metabolism within and between different types of cells. Transport reactions are used to account for the transfer of metabolites between models of different cell types via the interstitial fluid. We apply the method to create models of brain energy metabolism that recapitulate metabolic interactions between astrocytes and various neuron types relevant to Alzheimer's disease. Analysis of the models identifies genes and pathways that may explain observed experimental phenomena, including the differential effects of the disease on cell types and regions of the brain. Constraint-based modeling can thus contribute to the study and analysis of multicellular metabolic processes in the human tissue microenvironment and provide detailed mechanistic insight into high-throughput data analysis.

  17. Development of a Model for Whole Brain Learning of Physiology

    ERIC Educational Resources Information Center

    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…

  18. Exposure to Lipopolysaccharide and/or Unconjugated Bilirubin Impair the Integrity and Function of Brain Microvascular Endothelial Cells

    PubMed Central

    Cardoso, Filipa L.; Kittel, Ágnes; Veszelka, Szilvia; Palmela, Inês; Tóth, Andrea; Brites, Dora; Deli, Mária A.; Brito, Maria A.

    2012-01-01

    Background Sepsis and jaundice are common conditions in newborns that can lead to brain damage. Though lipopolysaccharide (LPS) is known to alter the integrity of the blood-brain barrier (BBB), little is known on the effects of unconjugated bilirubin (UCB) and even less on the joint effects of UCB and LPS on brain microvascular endothelial cells (BMEC). Methodology/Principal Findings Monolayers of primary rat BMEC were treated with 1 µg/ml LPS and/or 50 µM UCB, in the presence of 100 µM human serum albumin, for 4 or 24 h. Co-cultures of BMEC with astroglial cells, a more complex BBB model, were used in selected experiments. LPS led to apoptosis and UCB induced both apoptotic and necrotic-like cell death. LPS and UCB led to inhibition of P-glycoprotein and activation of matrix metalloproteinases-2 and -9 in mono-cultures. Transmission electron microscopy evidenced apoptotic bodies, as well as damaged mitochondria and rough endoplasmic reticulum in BMEC by either insult. Shorter cell contacts and increased caveolae-like invaginations were noticeable in LPS-treated cells and loss of intercellular junctions was observed upon treatment with UCB. Both compounds triggered impairment of endothelial permeability and transendothelial electrical resistance both in mono- and co-cultures. The functional changes were confirmed by alterations in immunostaining for junctional proteins β-catenin, ZO-1 and claudin-5. Enlargement of intercellular spaces, and redistribution of junctional proteins were found in BMEC after exposure to LPS and UCB. Conclusions LPS and/or UCB exert direct toxic effects on BMEC, with distinct temporal profiles and mechanisms of action. Therefore, the impairment of brain endothelial integrity upon exposure to these neurotoxins may favor their access to the brain, thus increasing the risk of injury and requiring adequate clinical management of sepsis and jaundice in the neonatal period. PMID:22586454

  19. Adolescent Emotional Maturation through Divergent Models of Brain Organization.

    PubMed

    Oron Semper, Jose V; Murillo, Jose I; Bernacer, Javier

    2016-01-01

    In this article we introduce the hypothesis that neuropsychological adolescent maturation, and in particular emotional management, may have opposing explanations depending on the interpretation of the assumed brain architecture, that is, whether a componential computational account (CCA) or a dynamic systems perspective (DSP) is used. According to CCA, cognitive functions are associated with the action of restricted brain regions, and this association is temporally stable; by contrast, DSP argues that cognitive functions are better explained by interactions between several brain areas, whose engagement in specific functions is temporal and context-dependent and based on neural reuse. We outline the main neurobiological facts about adolescent maturation, focusing on the neuroanatomical and neurofunctional processes associated with adolescence. We then explain the importance of emotional management in adolescent maturation. We explain the interplay between emotion and cognition under the scope of CCA and DSP, both at neural and behavioral levels. Finally, we justify why, according to CCA, emotional management is understood as regulation, specifically because the cognitive aspects of the brain are in charge of regulating emotion-related modules. However, the key word in DSP is integration, since neural information from different brain areas is integrated from the beginning of the process. Consequently, although the terms should not be conceptually confused, there is no cognition without emotion, and vice versa. Thus, emotional integration is not an independent process that just happens to the subject, but a crucial part of personal growth. Considering the importance of neuropsychological research in the development of educational and legal policies concerning adolescents, we intend to expose that the holistic view of adolescents is dependent on whether one holds the implicit or explicit interpretation of brain functioning.

  20. Adolescent Emotional Maturation through Divergent Models of Brain Organization

    PubMed Central

    Oron Semper, Jose V.; Murillo, Jose I.; Bernacer, Javier

    2016-01-01

    In this article we introduce the hypothesis that neuropsychological adolescent maturation, and in particular emotional management, may have opposing explanations depending on the interpretation of the assumed brain architecture, that is, whether a componential computational account (CCA) or a dynamic systems perspective (DSP) is used. According to CCA, cognitive functions are associated with the action of restricted brain regions, and this association is temporally stable; by contrast, DSP argues that cognitive functions are better explained by interactions between several brain areas, whose engagement in specific functions is temporal and context-dependent and based on neural reuse. We outline the main neurobiological facts about adolescent maturation, focusing on the neuroanatomical and neurofunctional processes associated with adolescence. We then explain the importance of emotional management in adolescent maturation. We explain the interplay between emotion and cognition under the scope of CCA and DSP, both at neural and behavioral levels. Finally, we justify why, according to CCA, emotional management is understood as regulation, specifically because the cognitive aspects of the brain are in charge of regulating emotion-related modules. However, the key word in DSP is integration, since neural information from different brain areas is integrated from the beginning of the process. Consequently, although the terms should not be conceptually confused, there is no cognition without emotion, and vice versa. Thus, emotional integration is not an independent process that just happens to the subject, but a crucial part of personal growth. Considering the importance of neuropsychological research in the development of educational and legal policies concerning adolescents, we intend to expose that the holistic view of adolescents is dependent on whether one holds the implicit or explicit interpretation of brain functioning. PMID:27602012

  1. Image guided constitutive modeling of the silicone brain phantom

    NASA Astrophysics Data System (ADS)

    Puzrin, Alexander; Skrinjar, Oskar; Ozan, Cem; Kim, Sihyun; Mukundan, Srinivasan

    2005-04-01

    The goal of this work is to develop reliable constitutive models of the mechanical behavior of the in-vivo human brain tissue for applications in neurosurgery. We propose to define the mechanical properties of the brain tissue in-vivo, by taking the global MR or CT images of a brain response to ventriculostomy - the relief of the elevated intracranial pressure. 3D image analysis translates these images into displacement fields, which by using inverse analysis allow for the constitutive models of the brain tissue to be developed. We term this approach Image Guided Constitutive Modeling (IGCM). The presented paper demonstrates performance of the IGCM in the controlled environment: on the silicone brain phantoms closely simulating the in-vivo brain geometry, mechanical properties and boundary conditions. The phantom of the left hemisphere of human brain was cast using silicon gel. An inflatable rubber membrane was placed inside the phantom to model the lateral ventricle. The experiments were carried out in a specially designed setup in a CT scanner with submillimeter isotropic voxels. The non-communicative hydrocephalus and ventriculostomy were simulated by consequently inflating and deflating the internal rubber membrane. The obtained images were analyzed to derive displacement fields, meshed, and incorporated into ABAQUS. The subsequent Inverse Finite Element Analysis (based on Levenberg-Marquardt algorithm) allowed for optimization of the parameters of the Mooney-Rivlin non-linear elastic model for the phantom material. The calculated mechanical properties were consistent with those obtained from the element tests, providing justification for the future application of the IGCM to in-vivo brain tissue.

  2. Integrated and Contextual Basic Science Instruction in Preclinical Education: Problem-Based Learning Experience Enriched with Brain/Mind Learning Principles

    ERIC Educational Resources Information Center

    Gülpinar, Mehmet Ali; Isoglu-Alkaç, Ümmühan; Yegen, Berrak Çaglayan

    2015-01-01

    Recently, integrated and contextual learning models such as problem-based learning (PBL) and brain/mind learning (BML) have become prominent. The present study aimed to develop and evaluate a PBL program enriched with BML principles. In this study, participants were 295 first-year medical students. The study used both quantitative and qualitative…

  3. Social Outcomes in Childhood Brain Disorder: A Heuristic Integration of Social Neuroscience and Developmental Psychology

    ERIC Educational Resources Information Center

    Yeates, Keith Owen; Bigler, Erin D.; Dennis, Maureen; Gerhardt, Cynthia A.; Rubin, Kenneth H.; Stancin, Terry; Taylor, H. Gerry; Vannatta, Kathryn

    2007-01-01

    The authors propose a heuristic model of the social outcomes of childhood brain disorder that draws on models and methods from both the emerging field of social cognitive neuroscience and the study of social competence in developmental psychology/psychopathology. The heuristic model characterizes the relationships between social adjustment, peer…

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

    PubMed Central

    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. A new computational approach for modeling diffusion tractography in the brain

    PubMed Central

    Garimella, Harsha T.; Kraft, Reuben H.

    2017-01-01

    Computational models provide additional tools for studying the brain, however, many techniques are currently disconnected from each other. There is a need for new computational approaches that span the range of physics operating in the brain. In this review paper, we offer some new perspectives on how the embedded element method can fill this gap and has the potential to connect a myriad of modeling genre. The embedded element method is a mesh superposition technique used within finite element analysis. This method allows for the incorporation of axonal fiber tracts to be explicitly represented. Here, we explore the use of the approach beyond its original goal of predicting axonal strain in brain injury. We explore the potential application of the embedded element method in areas of electrophysiology, neurodegeneration, neuropharmacology and mechanobiology. We conclude that this method has the potential to provide us with an integrated computational framework that can assist in developing improved diagnostic tools and regeneration technologies. PMID:28250733

  6. A new computational approach for modeling diffusion tractography in the brain.

    PubMed

    Garimella, Harsha T; Kraft, Reuben H

    2017-01-01

    Computational models provide additional tools for studying the brain, however, many techniques are currently disconnected from each other. There is a need for new computational approaches that span the range of physics operating in the brain. In this review paper, we offer some new perspectives on how the embedded element method can fill this gap and has the potential to connect a myriad of modeling genre. The embedded element method is a mesh superposition technique used within finite element analysis. This method allows for the incorporation of axonal fiber tracts to be explicitly represented. Here, we explore the use of the approach beyond its original goal of predicting axonal strain in brain injury. We explore the potential application of the embedded element method in areas of electrophysiology, neurodegeneration, neuropharmacology and mechanobiology. We conclude that this method has the potential to provide us with an integrated computational framework that can assist in developing improved diagnostic tools and regeneration technologies.

  7. Senescence-accelerated Mice (SAMs) as a Model for Brain Aging and Immunosenescence

    PubMed Central

    Shimada, Atsuyoshi; Hasegawa-Ishii, Sanae

    2011-01-01

    The Senescence-Accelerated Mouse (SAM) represents a group of inbred mouse strains developed as a model for the study of human aging and age-related diseases. Senescence-prone (SAMP) strains exhibit an early onset of age-related decline in the peripheral immunity such as thymic involution, loss of CD4+ T cells, impaired helper T cell function, decreased antibody-forming capacity, dysfunction of antigen-presenting cells, decreased natural killer activity, increased auto-antibodies, and susceptibility to virus infection. Senescence-prone SAMP10 mice undergo age-related changes in the brain such as brain atrophy, shrinkage and loss of cortical neurons, retraction of cortical neuronal dendrites, loss of dendritic spines, loss of synapses, impaired learning and memory, depressive behavior, accumulation of neuronal DNA damage, neuronal ubiquitinated inclusions, reduced hippocampal cholinergic receptors, decreased neurotrophic factors, decreased hippocampal zinc and zinc transporters, increased sphyngomyelinase, and elevated oxidative-nitrative stress. Recent data indicating increased pro-inflammatory cytokines in the brain of SAMP10 mice are directing investigators toward an integration of immune and neural abnormalities to enhance understanding of the principles of brain aging. We highlight how mouse brain cells adopt cytokine-mediated responses and how SAMP10 mice are defective in these responses. SAMP10 model would be useful to study how age-related disturbances in peripheral immunity have an impact on dysregulation of brain tissue homeostasis, resulting in age-related neurodegeneration. PMID:22396891

  8. Neurodynamic models of brain in psychiatry.

    PubMed

    Freeman, Walter J

    2003-07-01

    The history of brain theory is described in terms of three kinds of theory of perception. The most widely used kind sees perception as dependent on passive inflow from the environment of information that is used to make and process representations of objects and events. A second kind views perception as an active search for information that is inherent in the environment and is extracted by tuned resonances in brain circuits. A third kind holds that perception works by the creation of information through chaotic dynamics by forming hypotheses about the environment, through which learning takes place. Experimental evidence for creative dynamics in brains is briefly sketched. The explanation is offered that brains, being finite systems, work this way in order to cope with the infinite complexity of the world. All that brains can know is the hypotheses they construct and the results of testing them by acting into the environment, and learning by assimilation from the sensory consequences of their actions. The process is described as intentionality. It works through the action-perception-assimilation cycle. The cost of this solution to the problem of infinite complexity by hypothesis testing is the progressive isolation of individuals, as they accumulate their unique experiences through which their personalities form. Socialization and the acquisition of shared knowledge requires the emergence of new personality structure by self-organization through chaotic dissolution of existing the structure, as a prelude to the creation of new traits, habits, and values. Dissolution works in a crisis situation by regression to earlier stages of development, from which a fresh start can be made. A state of malleability emerges in the depth of crisis, in which compassionate companions through loving care can invite cooperative actions. Joint actions support the growth of a new lifestyle based on trust. Socialization requires neurochemical mechanisms of affiliation and bonding that

  9. An introduction to Space Weather Integrated Modeling

    NASA Astrophysics Data System (ADS)

    Zhong, D.; Feng, X.

    2012-12-01

    The need for a software toolkit that integrates space weather models and data is one of many challenges we are facing with when applying the models to space weather forecasting. To meet this challenge, we have developed Space Weather Integrated Modeling (SWIM) that is capable of analysis and visualizations of the results from a diverse set of space weather models. SWIM has a modular design and is written in Python, by using NumPy, matplotlib, and the Visualization ToolKit (VTK). SWIM provides data management module to read a variety of spacecraft data products and a specific data format of Solar-Interplanetary Conservation Element/Solution Element MHD model (SIP-CESE MHD model) for the study of solar-terrestrial phenomena. Data analysis, visualization and graphic user interface modules are also presented in a user-friendly way to run the integrated models and visualize the 2-D and 3-D data sets interactively. With these tools we can locally or remotely analysis the model result rapidly, such as extraction of data on specific location in time-sequence data sets, plotting interplanetary magnetic field lines, multi-slicing of solar wind speed, volume rendering of solar wind density, animation of time-sequence data sets, comparing between model result and observational data. To speed-up the analysis, an in-situ visualization interface is used to support visualizing the data 'on-the-fly'. We also modified some critical time-consuming analysis and visualization methods with the aid of GPU and multi-core CPU. We have used this tool to visualize the data of SIP-CESE MHD model in real time, and integrated the Database Model of shock arrival, Shock Propagation Model, Dst forecasting model and SIP-CESE MHD model developed by SIGMA Weather Group at State Key Laboratory of Space Weather/CAS.

  10. Brain-derived neurotrophic factor blood levels in two models of transient brain ischemia in rats.

    PubMed

    Gottlieb, Miroslav; Bonova, Petra; Danielisova, Viera; Nemethova, Miroslava; Burda, Jozef; Cizkova, Dasa

    2013-03-01

    We monitored possible influence of transient focal and global brain ischemia on BDNF blood level. In both models noticeable fluctuation of BDNF concentration mainly in reperfusion was observed. During the first 90 min, BDNF in total blood and in blood cells continuously decreased in both models but plasma BDNF raised at 40 min and peaked at 90 min of reperfusion. Our data confirm the impact of transient brain ischemia on BDNF levels in the circulatory system, suggest blood cells as a possible source of BDNF and demonstrate the interdependence of blood compartments and physiological state of an affected organism.

  11. [Animal models of injury and repair in developing brain].

    PubMed

    Cuestas, Eduardo; Caceres, Alfredo; Palacio, Santiago

    2007-01-01

    Animal models of injury and repair in developing brain. Brain injury is a major contributor to neonatal morbidity and mortality, a considerable group of these children will develop long term neurological sequels. Despite the great clinical and social significance and the advances in neonatal medicine, no therapy yet does exist that prevent or decrease detrimental effects in cases of neonatal brain injury. Our objective was to review recent research in relation to the hypothesis for repair mechanism in the developing brain, based in animal models that show developmental compensatory mechanisms that promote neural and functional plasticity. A better understanding of these adaptive mechanisms will help clinicians to apply knowledge derived from animals to human clinical situations.

  12. Canine brain tumours: a model for the human disease?

    PubMed

    Hicks, J; Platt, S; Kent, M; Haley, A

    2017-03-01

    Canine brain tumours are becoming established as naturally occurring models of disease to advance diagnostic and therapeutic understanding successfully. The size and structure of the dog's brain, histopathology and molecular characteristics of canine brain tumours, as well as the presence of an intact immune system, all support the potential success of this model. The limited success of current therapeutic regimens such as surgery and radiation for dogs with intracranial tumours means that there can be tremendous mutual benefit from collaboration with our human counterparts resulting in the development of new treatments. The similarities and differences between the canine and human diseases are described in this article, emphasizing both the importance and limitations of canines in brain tumour research. Recent clinical veterinary therapeutic trials are also described to demonstrate the areas of research in which canines have already been utilized and to highlight the important potential benefits of translational research to companion dogs.

  13. Biothermal Model of Patient and Automatic Control System of Brain Temperature for Brain Hypothermia Treatment

    NASA Astrophysics Data System (ADS)

    Wakamatsu, Hidetoshi; Gaohua, Lu

    Various surface-cooling apparatus such as the cooling cap, muffler and blankets have been commonly used for the cooling of the brain to provide hypothermic neuro-protection for patients of hypoxic-ischemic encephalopathy. The present paper is aimed at the brain temperature regulation from the viewpoint of automatic system control, in order to help clinicians decide an optimal temperature of the cooling fluid provided for these three types of apparatus. At first, a biothermal model characterized by dynamic ambient temperatures is constructed for adult patient, especially on account of the clinical practice of hypothermia and anesthesia in the brain hypothermia treatment. Secondly, the model is represented by the state equation as a lumped parameter linear dynamic system. The biothermal model is justified from their various responses corresponding to clinical phenomena and treatment. Finally, the optimal regulator is tentatively designed to give clinicians some suggestions on the optimal temperature regulation of the patient’s brain. It suggests the patient’s brain temperature could be optimally controlled to follow-up the temperature process prescribed by the clinicians. This study benefits us a great clinical possibility for the automatic hypothermia treatment.

  14. Integrative analysis of the connectivity and gene expression atlases in the mouse brain.

    PubMed

    Ji, Shuiwang; Fakhry, Ahmed; Deng, Houtao

    2014-01-01

    Brain function is the result of interneuron signal transmission controlled by the fundamental biochemistry of each neuron. The biochemical content of a neuron is in turn determined by spatiotemporal gene expression and regulation encoded into the genomic regulatory networks. It is thus of particular interest to elucidate the relationship between gene expression patterns and connectivity in the brain. However, systematic studies of this relationship in a single mammalian brain are lacking to date. Here, we investigate this relationship in the mouse brain using the Allen Brain Atlas data. We employ computational models for predicting brain connectivity from gene expression data. In addition to giving competitive predictive performance, these models can rank the genes according to their predictive power. We show that gene expression is predictive of connectivity in the mouse brain when the connectivity signals are discretized. When the expression patterns of 4084 genes are used, we obtain a predictive accuracy of 93%. Our results also show that a small number of genes can almost give the full predictive power of using thousands of genes. We can achieve a prediction accuracy of 91% by using only 25 genes. Gene ontology analysis of the highly ranked genes shows that they are enriched for connectivity related processes.

  15. Central artery stiffness, baroreflex sensitivity, and brain white matter neuronal fiber integrity in older adults.

    PubMed

    Tarumi, Takashi; de Jong, Daan L K; Zhu, David C; Tseng, Benjamin Y; Liu, Jie; Hill, Candace; Riley, Jonathan; Womack, Kyle B; Kerwin, Diana R; Lu, Hanzhang; Munro Cullum, C; Zhang, Rong

    2015-04-15

    Cerebral hypoperfusion elevates the risk of brain white matter (WM) lesions and cognitive impairment. Central artery stiffness impairs baroreflex, which controls systemic arterial perfusion, and may deteriorate neuronal fiber integrity of brain WM. The purpose of this study was to examine the associations among brain WM neuronal fiber integrity, baroreflex sensitivity (BRS), and central artery stiffness in older adults. Fifty-four adults (65 ± 6 years) with normal cognitive function or mild cognitive impairment (MCI) were tested. The neuronal fiber integrity of brain WM was assessed from diffusion metrics acquired by diffusion tensor imaging. BRS was measured in response to acute changes in blood pressure induced by bolus injections of vasoactive drugs. Central artery stiffness was measured by carotid-femoral pulse wave velocity (cfPWV). The WM diffusion metrics including fractional anisotropy (FA) and radial (RD) and axial (AD) diffusivities, BRS, and cfPWV were not different between the control and MCI groups. Thus, the data from both groups were combined for subsequent analyses. Across WM, fiber tracts with decreased FA and increased RD were associated with lower BRS and higher cfPWV, with many of the areas presenting spatial overlap. In particular, the BRS assessed during hypotension was strongly correlated with FA and RD when compared with hypertension. Executive function performance was associated with FA and RD in the areas that correlated with cfPWV and BRS. These findings suggest that baroreflex-mediated control of systemic arterial perfusion, especially during hypotension, may play a crucial role in maintaining neuronal fiber integrity of brain WM in older adults.

  16. Modeling for System Integration Studies (Presentation)

    SciTech Connect

    Orwig, K. D.

    2012-05-01

    This presentation describes some the data requirements needed for grid integration modeling and provides real-world examples of such data and its format. Renewable energy integration studies evaluate the operational impacts of variable generation. Transmission planning studies investigate where new transmission is needed to transfer energy from generation sources to load centers. Both use time-synchronized wind and solar energy production and load as inputs. Both examine high renewable energy penetration scenarios in the future.

  17. Efficacy of cabazitaxel in mouse models of pediatric brain tumors

    PubMed Central

    Girard, Emily; Ditzler, Sally; Lee, Donghoon; Richards, Andrew; Yagle, Kevin; Park, Joshua; Eslamy, Hedieh; Bobilev, Dmitri; Vrignaud, Patricia; Olson, James

    2015-01-01

    Background There is an unmet need in the treatment of pediatric brain tumors for chemotherapy that is efficacious, avoids damage to the developing brain, and crosses the blood-brain barrier. These experiments evaluated the efficacy of cabazitaxel in mouse models of pediatric brain tumors. Methods The antitumor activity of cabazitaxel and docetaxel were compared in flank and orthotopic xenograft models of patient-derived atypical teratoid rhabdoid tumor (ATRT), medulloblastoma, and central nervous system primitive neuroectodermal tumor (CNS-PNET). Efficacy of cabazitaxel and docetaxel were also assessed in the Smo/Smo spontaneous mouse medulloblastoma tumor model. Results This study observed significant tumor growth inhibition in pediatric patient-derived flank xenograft tumor models of ATRT, medulloblastoma, and CNS-PNET after treatment with either cabazitaxel or docetaxel. Cabazitaxel, but not docetaxel, treatment resulted in sustained tumor growth inhibition in the ATRT and medulloblastoma flank xenograft models. Patient-derived orthotopic xenograft models of ATRT, medulloblastoma, and CNS-PNET showed significantly improved survival with treatment of cabazitaxel. Conclusion These data support further testing of cabazitaxel as a therapy for treating human pediatric brain tumors. PMID:25140037

  18. Beyond Neural Cubism: Promoting a Multidimensional View of Brain Disorders by Enhancing the Integration of Neurology and Psychiatry in Education

    PubMed Central

    Taylor, Joseph J.; Williams, Nolan R.; George, Mark S.

    2014-01-01

    Cubism was an influential early 20th century art movement characterized by angular, disjointed imagery. The two-dimensional appearance of Cubist figures and objects is created through juxtaposition of angles. The authors posit that the constrained perspectives found in Cubism may also be found in the clinical classification of brain disorders. Neurological disorders are often separated from psychiatric disorders as if they stem from different organ systems. Maintaining two isolated clinical disciplines fractionalizes the brain in the same way that Pablo Picasso fractionalized figures and objects in his Cubist art. This Neural Cubism perpetuates a clinical divide that does not reflect the scope and depth of neuroscience. All brain disorders are complex and multidimensional, with aberrant circuitry and resultant psychopharmacology manifesting as altered behavior, affect, mood or cognition. Trainees should receive a multidimensional education based on modern neuroscience, not a partial education based on clinical precedent. The authors briefly outline the rationale for increasing the integration of neurology and psychiatry and discuss a nested model with which clinical neuroscientists (neurologists and psychiatrists) can approach and treat brain disorders. PMID:25340364

  19. Beyond neural cubism: promoting a multidimensional view of brain disorders by enhancing the integration of neurology and psychiatry in education.

    PubMed

    Taylor, Joseph J; Williams, Nolan R; George, Mark S

    2015-05-01

    Cubism was an influential early-20th-century art movement characterized by angular, disjointed imagery. The two-dimensional appearance of Cubist figures and objects is created through juxtaposition of angles. The authors posit that the constrained perspectives found in Cubism may also be found in the clinical classification of brain disorders. Neurological disorders are often separated from psychiatric disorders as if they stemmed from different organ systems. Maintaining two isolated clinical disciplines fractionalizes the brain in the same way that Pablo Picasso fractionalized figures and objects in his Cubist art. This Neural Cubism perpetuates a clinical divide that does not reflect the scope and depth of neuroscience. All brain disorders are complex and multidimensional, with aberrant circuitry and resultant psychopharmacology manifesting as altered behavior, affect, mood, or cognition. Trainees should receive a multidimensional education based on modern neuroscience, not a partial education based on clinical precedent. The authors briefly outline the rationale for increasing the integration of neurology and psychiatry and discuss a nested model with which clinical neuroscientists (neurologists and psychiatrists) can approach and treat brain disorders.

  20. Neural mass model-based tracking of anesthetic brain states.

    PubMed

    Kuhlmann, Levin; Freestone, Dean R; Manton, Jonathan H; Heyse, Bjorn; Vereecke, Hugo E M; Lipping, Tarmo; Struys, Michel M R F; Liley, David T J

    2016-06-01

    Neural mass model-based tracking of brain states from electroencephalographic signals holds the promise of simultaneously tracking brain states while inferring underlying physiological changes in various neuroscientific and clinical applications. Here, neural mass model-based tracking of brain states using the unscented Kalman filter applied to estimate parameters of the Jansen-Rit cortical population model is evaluated through the application of propofol-based anesthetic state monitoring. In particular, 15 subjects underwent propofol anesthesia induction from awake to anesthetised while behavioral responsiveness was monitored and frontal electroencephalographic signals were recorded. The unscented Kalman filter Jansen-Rit model approach applied to frontal electroencephalography achieved reasonable testing performance for classification of the anesthetic brain state (sensitivity: 0.51; chance sensitivity: 0.17; nearest neighbor sensitivity 0.75) when compared to approaches based on linear (autoregressive moving average) modeling (sensitivity 0.58; nearest neighbor sensitivity: 0.91) and a high performing standard depth of anesthesia monitoring measure, Higuchi Fractal Dimension (sensitivity: 0.50; nearest neighbor sensitivity: 0.88). Moreover, it was found that the unscented Kalman filter based parameter estimates of the inhibitory postsynaptic potential amplitude varied in the physiologically expected direction with increases in propofol concentration, while the estimates of the inhibitory postsynaptic potential rate constant did not. These results combined with analysis of monotonicity of parameter estimates, error analysis of parameter estimates, and observability analysis of the Jansen-Rit model, along with considerations of extensions of the Jansen-Rit model, suggests that the Jansen-Rit model combined with unscented Kalman filtering provides a valuable reference point for future real-time brain state tracking studies. This is especially true for studies of

  1. Integrated radionuclide release: tests and model development (integrated testing)

    SciTech Connect

    Viani, B

    1995-08-07

    The Department of Energy's Yucca Mountain Site Characterization Project (YMP) is evaluating a site at Yucca Mountain, Nevada as a potential repository for the disposal of high-level nuclear waste. Credible bounding estimates of the type, concentration, and nature of the radionuclides that might potentially escape the engineered barrier system/near field environment (EBS/NFE) (i.e., the source term) are necessary prerequisites to assessing the expected performance of a po- tential repository. Estimating the source term will require a combination of experimental and modeling tasks that are designed to assess the release of radionclides from the waste form and their transport through and interaction with the components of the EBS/NFE. The Integrated Radionuclidc Release: Tests and Model Development activity (Integrated Testing) at Lawrence Liver-more National Laboratory (LLNL) is an experimental and modeling activity that is specifically concerned with radionuclide transport through and interaction with the compo- nents of the EBS/NFE. As such, this activity is the link b!etween waste-form degradation activities and far-field transport activities. Performance analysis of the EBS/NFE subsystem is an important component of the total system performance analyses (TSPA) that will be used to evaluate reposi- tory performance.

  2. International summit on integrated environmental modeling

    USGS Publications Warehouse

    Gaber, Noha; Geller, Gary; Glynn, Pierre; Laniak, Gerry; Voinov, Alexey; Whelan, Gene; Roger, Moore; Hughes, Andrew

    2013-01-01

    This report describes the International Summit on Integrated Environmental Modeling (IEM), held in Reston, VA, on 7th-9th December 2010. The meeting brought together 57 scientists and managers from leading US and European government and non-governmental organizations, universities and companies together with international organizations convened over a number of years, including: the US Environmental Protection Agency (USEPA) workshop on Collaborative Approaches to Integrated Modeling: Better Integration for Better Decisionmaking (December, 2008); the AGU Fall Meeting, San Francisco (December 2009); and the International Congress on Environmental Modeling and Software (July 2010). From these meetings there is now recognition that many separate communities are involved in developing IEM. The aim of the Summit was to bring together two key groupings, the US and Europe, with the intention of creating a community open to all.

  3. Integrated Modelling - the next steps (Invited)

    NASA Astrophysics Data System (ADS)

    Moore, R. V.

    2010-12-01

    Integrated modelling (IM) has made considerable advances over the past decade but it has not yet been taken up as an operational tool in the way that its proponents had hoped. The reasons why will be discussed in Session U17. This talk will propose topics for a research and development programme and suggest an institutional structure which, together, could overcome the present obstacles. Their combined aim would be first to make IM into an operational tool useable by competent public authorities and commercial companies and, in time, to see it evolve into the modelling equivalent of Google Maps, something accessible and useable by anyone with a PC or an iphone and an internet connection. In a recent study, a number of government agencies, water authorities and utilities applied integrated modelling to operational problems. While the project demonstrated that IM could be used in an operational setting and had benefit, it also highlighted the advances that would be required for its widespread uptake. These were: greatly improving the ease with which models could be a) made linkable, b) linked and c) run; developing a methodology for applying integrated modelling; developing practical options for calibrating and validating linked models; addressing the science issues that arise when models are linked; extending the range of modelling concepts that can be linked; enabling interface standards to pass uncertainty information; making the interface standards platform independent; extending the range of platforms to include those for high performance computing; developing the concept of modelling components as web services; separating simulation code from the model’s GUI, so that all the results from the linked models can be viewed through a single GUI; developing scenario management systems so that that there is an audit trail of the version of each model and dataset used in each linked model run. In addition to the above, there is a need to build a set of integrated

  4. Brain inflammation and oxidative stress in a transgenic mouse model of Alzheimer-like brain amyloidosis

    PubMed Central

    Yao, Yuemang; Chinnici, Cinzia; Tang, Hanguan; Trojanowski, John Q; Lee, Virginia MY; Praticò, Domenico

    2004-01-01

    Background An increasing body of evidence implicates both brain inflammation and oxidative stress in the pathogenesis of Alzheimer's disease (AD). The relevance of their interaction in vivo, however, is unknown. Previously, we have shown that separate pharmacological targeting of these two components results in amelioration of the amyloidogenic phenotype of a transgenic mouse model of AD-like brain amyloidosis (Tg2576). Methods In the present study, we investigated the therapeutic effects of a combination of an anti-inflammatory agent, indomethacin, and a natural anti-oxidant, vitamin E, in the Tg2576 mice. For this reason, animals were treated continuously from 8 (prior to Aβ deposition) through 15 (when Aβ deposits are abundant) months of age. Results At the end of the study, these therapeutic interventions suppressed brain inflammatory and oxidative stress responses in the mice. This effect was accompanied by significant reductions of soluble and insoluble Aβ1-40 and Aβ1-42 in neocortex and hippocampus, wherein the burden of Aβ deposits also was significantly decreased. Conclusions The results of the present study support the concept that brain oxidative stress and inflammation coexist in this animal model of AD-like brain amyloidosis, but they represent two distinct therapeutic targets in the disease pathogenesis. We propose that a combination of anti-inflammatory and anti-oxidant drugs may be a useful strategy for treating AD. PMID:15500684

  5. Thermal imaging of brain tumors in a rat glioma model

    NASA Astrophysics Data System (ADS)

    Papaioannou, Thanassis; Thompson, Reid C.; Kateb, Babak; Sorokoumov, Oleg; Grundfest, Warren S.; Black, Keith L.

    2002-05-01

    We have explored the capability of thermal imaging for the detection of brain tumors in a rat glioma mode. Fourteen Wistar rats were injected stereotactically with 100,000 C6 glioma cells. Approximately one and two weeks post implantation, the rats underwent bilateral craniotomy and the exposed brain surface was imaged with a short wave thermal camera. Thermal images were obtained at both low (approximately 28.7 degree(s)C) and high (approximately 38 degree(s)C) core temperatures. Temperature gradients between the tumor site and the contralateral normal brain were calculated. Overall, the tumors appeared cooler than normal brain, for both high and low core temperatures. Average temperature difference between tumor and normal brain were maximal in more advanced tumors (two weeks) and at higher core temperatures. At one week (N equals 6), the average temperature gradient between tumor and normal sites was 0.1 degree(s)C and 0.2 degree(s)C at low and high core temperatures respectively (P(greater than)0.05). At two weeks (N equals 8), the average temperature gradient was 0.3 degree(s)C and 0.7 degree(s)C at low and high core temperatures respectively (P<0.05). We conclude that thermal imaging can detect temperature differences between tumor and normal brain tissue in this model, particularly in more advanced tumors. Thermal imaging may provide a novel means to identify brain tumors intraoperatively.

  6. Dynamical Signatures of Structural Connectivity Damage to a Model of the Brain Posed at Criticality.

    PubMed

    Haimovici, Ariel; Balenzuela, Pablo; Tagliazucchi, Enzo

    2016-12-01

    Synchronization of brain activity fluctuations is believed to represent communication between spatially distant neural processes. These interareal functional interactions develop in the background of a complex network of axonal connections linking cortical and subcortical neurons, termed the human "structural connectome." Theoretical considerations and experimental evidence support the view that the human brain can be modeled as a system operating at a critical point between ordered (subcritical) and disordered (supercritical) phases. Here, we explore the hypothesis that pathologies resulting from brain injury of different etiologies are related to this model of a critical brain. For this purpose, we investigate how damage to the integrity of the structural connectome impacts on the signatures of critical dynamics. Adopting a hybrid modeling approach combining an empirical weighted network of human structural connections with a conceptual model of critical dynamics, we show that lesions located at highly transited connections progressively displace the model toward the subcritical regime. The topological properties of the nodes and links are of less importance when considered independently of their weight in the network. We observe that damage to midline hubs such as the middle and posterior cingulate cortex is most crucial for the disruption of criticality in the model. However, a similar effect can be achieved by targeting less transited nodes and links whose connection weights add up to an equivalent amount. This implies that brain pathology does not necessarily arise due to insult targeted at well-connected areas and that intersubject variability could obscure lesions located at nonhub regions. Finally, we discuss the predictions of our model in the context of clinical studies of traumatic brain injury and neurodegenerative disorders.

  7. Integrable Deformations of T -Dual σ Models

    NASA Astrophysics Data System (ADS)

    Borsato, Riccardo; Wulff, Linus

    2016-12-01

    We present a method to deform (generically non-Abelian) T duals of two-dimensional σ models, which preserves classical integrability. The deformed models are identified by a linear operator ω on the dualized subalgebra, which satisfies the 2-cocycle condition. We prove that the so-called homogeneous Yang-Baxter deformations are equivalent, via a field redefinition, to our deformed models when ω is invertible. We explain the details for deformations of T duals of principal chiral models, and present the corresponding generalization to the case of supercoset models.

  8. Integrated facilities modeling using QUEST and IGRIP

    SciTech Connect

    Davis, K.R.; Haan, E.R.

    1995-08-01

    A QUEST model and associated detailed IGRIP models were developed and used to simulate several workcells in a proposed Plutonium Storage Facility (PSF). The models are being used by team members assigned to the program to improve communication and to assist in evaluating concepts and in performing trade-off studies which will result in recommendations and a final design. The model was designed so that it could be changed easily. The added flexibility techniques used to make changes easily are described in this paper in addition to techniques for integrating the QUEST and IGRIP products. Many of these techniques are generic in nature and can be applied to any modeling endeavor.

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

    PubMed

    Budday, Silvia; Raybaud, Charles; Kuhl, Ellen

    2014-07-10

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

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

    PubMed Central

    Budday, Silvia; Raybaud, Charles; Kuhl, Ellen

    2014-01-01

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

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

    NASA Astrophysics Data System (ADS)

    Budday, Silvia; Raybaud, Charles; Kuhl, Ellen

    2014-07-01

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

  12. Mathematical framework for large-scale brain network modeling in The Virtual Brain.

    PubMed

    Sanz-Leon, Paula; Knock, Stuart A; Spiegler, Andreas; Jirsa, Viktor K

    2015-05-01

    In this article, we describe the mathematical framework of the computational model at the core of the tool The Virtual Brain (TVB), designed to simulate collective whole brain dynamics by virtualizing brain structure and function, allowing simultaneous outputs of a number of experimental modalities such as electro- and magnetoencephalography (EEG, MEG) and functional Magnetic Resonance Imaging (fMRI). The implementation allows for a systematic exploration and manipulation of every underlying component of a large-scale brain network model (BNM), such as the neural mass model governing the local dynamics or the structural connectivity constraining the space time structure of the network couplings. Here, a consistent notation for the generalized BNM is given, so that in this form the equations represent a direct link between the mathematical description of BNMs and the components of the numerical implementation in TVB. Finally, we made a summary of the forward models implemented for mapping simulated neural activity (EEG, MEG, sterotactic electroencephalogram (sEEG), fMRI), identifying their advantages and limitations.

  13. Systems integrity in health and aging - an animal model approach

    PubMed Central

    2013-01-01

    Human lifespan is positively correlated with childhood intelligence, as measured by psychometric (IQ) tests. The strength of this correlation is similar to the negative effect that smoking has on the life course. This result suggests that people who perform well on psychometric tests in childhood may remain healthier and live longer. The correlation, however, is debated: is it caused exclusively by social-environmental factors or could it also have a biological component? Biological traits of systems integrity that might result in correlations between brain function and lifespan have been suggested but are not well-established, and it is questioned what useful knowledge can come from understanding such mechanisms. In a recent study, we found a positive correlation between brain function and longevity in honey bees. Honey bees are highly social, but relevant social-environmental factors that contribute to cognition-survival correlations in humans are largely absent from insect colonies. Our results, therefore, suggest a biological explanation for the correlation in the bee. Here, we argue that individual differences in stress handling (coping) mechanisms, which both affect the bees’ performance in tests of brain function and their survival could be a trait of systems integrity. Individual differences in coping are much studied in vertebrates, and several species provide attractive models. Here, we discuss how pigs are an interesting model for studying behavioural, physiological and molecular mechanisms that are recruited during stress and that can drive correlations between health, cognition and longevity traits. By revealing biological factors that make individuals susceptible to stress, it might be possible to alleviate health and longevity disparities in people. PMID:24472488

  14. The Segregation and Integration of Distinct Brain Networks and Their Relationship to Cognition.

    PubMed

    Cohen, Jessica R; D'Esposito, Mark

    2016-11-30

    A critical feature of the human brain that gives rise to complex cognition is its ability to reconfigure its network structure dynamically and adaptively in response to the environment. Existing research probing task-related reconfiguration of brain network structure has concluded that, although there are many similarities in network structure during an intrinsic, resting state and during the performance of a variety of cognitive tasks, there are meaningful differences as well. In this study, we related intrinsic, resting state network organization to reconfigured network organization during the performance of two tasks: a sequence tapping task, which is thought to probe motor execution and likely engages a single brain network, and an n-back task, which is thought to probe working memory and likely requires coordination across multiple networks. We implemented graph theoretical analyses using functional connectivity data from fMRI scans to calculate whole-brain measures of network organization in healthy young adults. We focused on quantifying measures of network segregation (modularity, system segregation, local efficiency, number of provincial hub nodes) and measures of network integration (global efficiency, number of connector hub nodes). Using these measures, we found converging evidence that local, within-network communication is critical for motor execution, whereas integrative, between-network communication is critical for working memory. These results confirm that the human brain has the remarkable ability to reconfigure its large-scale organization dynamically in response to current cognitive demands and that interpreting reconfiguration in terms of network segregation and integration may shed light on the optimal network structures underlying successful cognition.

  15. CTBT integrated verification system evaluation model supplement

    SciTech Connect

    EDENBURN,MICHAEL W.; BUNTING,MARCUS; PAYNE JR.,ARTHUR C.; TROST,LAWRENCE C.

    2000-03-02

    Sandia National Laboratories has developed a computer based model called IVSEM (Integrated Verification System Evaluation Model) to estimate the performance of a nuclear detonation monitoring system. The IVSEM project was initiated in June 1994, by Sandia's Monitoring Systems and Technology Center and has been funded by the U.S. Department of Energy's Office of Nonproliferation and National Security (DOE/NN). IVSEM is a simple, ''top-level,'' modeling tool which estimates the performance of a Comprehensive Nuclear Test Ban Treaty (CTBT) monitoring system and can help explore the impact of various sensor system concepts and technology advancements on CTBT monitoring. One of IVSEM's unique features is that it integrates results from the various CTBT sensor technologies (seismic, in sound, radionuclide, and hydroacoustic) and allows the user to investigate synergy among the technologies. Specifically, IVSEM estimates the detection effectiveness (probability of detection), location accuracy, and identification capability of the integrated system and of each technology subsystem individually. The model attempts to accurately estimate the monitoring system's performance at medium interfaces (air-land, air-water) and for some evasive testing methods such as seismic decoupling. The original IVSEM report, CTBT Integrated Verification System Evaluation Model, SAND97-25 18, described version 1.2 of IVSEM. This report describes the changes made to IVSEM version 1.2 and the addition of identification capability estimates that have been incorporated into IVSEM version 2.0.

  16. Data and Model Integration Promoting Interdisciplinarity

    NASA Astrophysics Data System (ADS)

    Koike, T.

    2014-12-01

    It is very difficult to reflect accumulated subsystem knowledge into holistic knowledge. Knowledge about a whole system can rarely be introduced into a targeted subsystem. In many cases, knowledge in one discipline is inapplicable to other disciplines. We are far from resolving cross-disciplinary issues. It is critically important to establish interdisciplinarity so that scientific knowledge can transcend disciplines. We need to share information and develop knowledge interlinkages by building models and exchanging tools. We need to tackle a large increase in the volume and diversity of data from observing the Earth. The volume of data stored has exponentially increased. Previously, almost all of the large-volume data came from satellites, but model outputs occupy the largest volume in general. To address the large diversity of data, we should develop an ontology system for technical and geographical terms in coupling with a metadata design according to international standards. In collaboration between Earth environment scientists and IT group, we should accelerate data archiving by including data loading, quality checking and metadata registration, and enrich data-searching capability. DIAS also enables us to perform integrated research and realize interdisciplinarity. For example, climate change should be addressed in collaboration between the climate models, integrated assessment models including energy, economy, agriculture, health, and the models of adaptation, vulnerability, and human settlement and infrastructure. These models identify water as central to these systems. If a water expert can develop an interrelated system including each component, the integrated crisis can be addressed by collaboration with various disciplines. To realize this purpose, we are developing a water-related data- and model-integration system called a water cycle integrator (WCI).

  17. C5a alters blood-brain barrier integrity in experimental lupus.

    PubMed

    Jacob, Alexander; Hack, Bradley; Chiang, Eddie; Garcia, Joe G N; Quigg, Richard J; Alexander, Jessy J

    2010-06-01

    The blood-brain barrier (BBB) is a crucial anatomic location in the brain. Its dysfunction complicates many neurodegenerative diseases, from acute conditions, such as sepsis, to chronic diseases, such as systemic lupus erythematosus (SLE). Several studies suggest an altered BBB in lupus, but the underlying mechanism remains unknown. In the current study, we observed a definite loss of BBB integrity in MRL/MpJ-Tnfrsf6(lpr) (MRL/lpr) lupus mice by IgG infiltration into brain parenchyma. In line with this result, we examined the role of complement activation, a key event in this setting, in maintenance of BBB integrity. Complement activation generates C5a, a molecule with multiple functions. Because the expression of the C5a receptor (C5aR) is significantly increased in brain endothelial cells treated with lupus serum, the study focused on the role of C5a signaling through its G-protein-coupled receptor C5aR in brain endothelial cells, in a lupus setting. Reactive oxygen species production increased significantly in endothelial cells, in both primary cells and the bEnd3 cell line treated with lupus serum from MRL/lpr mice, compared with those treated with control serum from MRL(+/+) mice. In addition, increased permeability monitored by changes in transendothelial electrical resistance, cytoskeletal remodeling caused by actin fiber rearrangement, and increased iNOS mRNA expression were observed in bEnd3 cells. These disruptive effects were alleviated by pretreating cells with a C5a receptor antagonist (C5aRant) or a C5a antibody. Furthermore, the structural integrity of the vasculature in MRL/lpr brain was maintained by C5aR inhibition. These results demonstrate the regulation of BBB integrity by the complement system in a neuroinflammatory setting. For the first time, a novel role of C5a in the maintenance of BBB integrity is identified and the potential of C5a/C5aR blockade highlighted as a promising therapeutic strategy in SLE and other neurodegenerative diseases.

  18. Predictive modeling of neuroanatomic structures for brain atrophy detection

    NASA Astrophysics Data System (ADS)

    Hu, Xintao; Guo, Lei; Nie, Jingxin; Li, Kaiming; Liu, Tianming

    2010-03-01

    In this paper, we present an approach of predictive modeling of neuroanatomic structures for the detection of brain atrophy based on cross-sectional MRI image. The underlying premise of applying predictive modeling for atrophy detection is that brain atrophy is defined as significant deviation of part of the anatomy from what the remaining normal anatomy predicts for that part. The steps of predictive modeling are as follows. The central cortical surface under consideration is reconstructed from brain tissue map and Regions of Interests (ROI) on it are predicted from other reliable anatomies. The vertex pair-wise distance between the predicted vertex and the true one within the abnormal region is expected to be larger than that of the vertex in normal brain region. Change of white matter/gray matter ratio within a spherical region is used to identify the direction of vertex displacement. In this way, the severity of brain atrophy can be defined quantitatively by the displacements of those vertices. The proposed predictive modeling method has been evaluated by using both simulated atrophies and MRI images of Alzheimer's disease.

  19. Task-specific functional brain geometry from model maps.

    PubMed

    Langs, Georg; Samaras, Dimitris; Paragios, Nikos; Honorio, Jean; Alia-Klein, Nelly; Tomasi, Dardo; Volkow, Nora D; Goldstein, Rita Z

    2008-01-01

    In this paper we propose model maps to derive and represent the intrinsic functional geometry of a brain from functional magnetic resonance imaging (fMRI) data for a specific task. Model maps represent the coherence of behavior of individual fMRI-measurements for a set of observations, or a time sequence. The maps establish a relation between individual positions in the brain by encoding the blood oxygen level dependent (BOLD) signal over a time period in a Markov chain. They represent this relation by mapping spatial positions to a new metric space, the model map. In this map the Euclidean distance between two points relates to the joint modeling behavior of their signals and thus the co-dependencies of the corresponding signals. The map reflects the functional as opposed to the anatomical geometry of the brain. It provides a quantitative tool to explore and study global and local patterns of resource allocation in the brain. To demonstrate the merit of this representation, we report quantitative experimental results on 29 fMRI time sequences, each with sub-sequences corresponding to 4 different conditions for two groups of individuals. We demonstrate that drug abusers exhibit lower differentiation in brain interactivity between baseline and reward related tasks, which could not be quantified until now.

  20. EEG-fMRI integration for the study of human brain function.

    PubMed

    Jorge, João; van der Zwaag, Wietske; Figueiredo, Patrícia

    2014-11-15

    Electroencephalography (EEG) and functional magnetic resonance imaging (fMRI) have proved to be extremely valuable tools for the non-invasive study of human brain function. Moreover, due to a notable degree of complementarity between the two modalities, the combination of EEG and fMRI data has been actively sought in the last two decades. Although initially focused on epilepsy, EEG-fMRI applications were rapidly extended to the study of healthy brain function, yielding new insights into its underlying mechanisms and pathways. Nevertheless, EEG and fMRI have markedly different spatial and temporal resolutions, and probe neuronal activity through distinct biophysical processes, many aspects of which are still poorly understood. The remarkable conceptual and methodological challenges associated with EEG-fMRI integration have motivated the development of a wide range of analysis approaches over the years, each relying on more or less restrictive assumptions, and aiming to shed further light on the mechanisms of brain function along with those of the EEG-fMRI coupling itself. Here, we present a review of the most relevant EEG-fMRI integration approaches yet proposed for the study of brain function, supported by a general overview of our current understanding of the biophysical mechanisms coupling the signals obtained from the two modalities.

  1. HIF-1α inhibition ameliorates neonatal brain injury in a rat pup hypoxic-ischemic model

    PubMed Central

    Chen, Wanqiu; Jadhav, Vikram; Tang, Jiping; Zhang, John H.

    2008-01-01

    Hypoxia-inducible factor-1alpha (HIF-1α) has been considered as a regulator of both prosurvival and prodeath pathways in the nervous system. The present study was designed to elucidate the role of HIF-1α in neonatal hypoxic-ischemic (HI) brain injury. Rice-Vannucci model of neonatal hypoxic-ischemic brain injury was used in seven-day-old rats, by subjecting unilateral carotid artery ligation followed by 2h of hypoxia (8% O2 at 37°C). HIF-1α activity was inhibited by 2-methoxyestradiol (2ME2) and enhanced by dimethyloxalylglycine (DMOG). Results showed that 2ME2 exhibited dose-dependent neuroprotection by decreasing infarct volume and reducing brain edema at 48 h post HI. The neuroprotection was lost when 2ME2 was administered 3 h post HI. HIF-1α upregulation by DMOG increased the permeability of the BBB and brain edema compared with HI group. 2ME2 attenuated the increase in HIF-1α and VEGF 24 h after HI. 2ME2 also had a long-term effect of protecting against the loss of brain tissue. The study showed that the early inhibition of HIF-1α acutely after injury provided neuroprotection after neonatal hypoxia-ischemia which was associated with preservation of BBB integrity, attenuation of brain edema, and neuronal death. PMID:18602008

  2. Models for predicting blood-brain barrier permeation.

    PubMed

    Nielsen, Peter Aadal; Andersson, Olga; Hansen, Steen Honoré; Simonsen, Klaus Bæk; Andersson, Gunnar

    2011-06-01

    The endothelial blood-brain barrier (BBB) ensures an optimal environment for proper neural function in vertebrates; however, it also creates a major obstacle for the medical treatment of brain diseases. Despite significant progress in the development of various in vitro and in silico models for predicting BBB permeation, many challenges remain and, so far, no model is able to meet the early drug discovery demands of the industry for reliability and time and cost efficiency. Recently, it was found that the grasshopper (Locusta migratoria) brain barrier has similar functionality as the vertebrate BBB. The insect model can thus be used as a surrogate for the vertebrate BBB as it meets the demands required during the drug discovery phase.

  3. Integrated odour modelling for sewage treatment works.

    PubMed

    Gostelow, P; Parsons, S A; Lovell, M

    2004-01-01

    Odours from sewage treatment works are a significant source of environmental annoyance. There is a need for tools to assess the degree of annoyance caused, and to assess strategies for mitigation of the problem. This is the role of odour modelling. Four main stages are important in the development of an odour problem. Firstly, the odorous molecules must be formed in the liquid phase. They must then transfer from the liquid to the gaseous phase. They are then transported through the atmosphere to the population surrounding the odour source, and are then perceived and assessed by that population. Odour modelling as currently practised tends to concentrate on the transportation of odorants through the atmosphere, with the other areas receiving less attention. Instead, odour modelling should consider each stage in an integrated manner. This paper describes the development of integrated odour models for annoyance prediction. The models describe the liquid-phase transformations and emission of hydrogen sulphide from sewage treatment processes. Model output is in a form suitable for integration with dispersion models, the predictions of which can in turn be used to indicate the probability of annoyance. The models have been applied to both hypothetical and real sewage treatment works cases. Simulation results have highlighted the potential variability of emission rates from sewage treatment works, resulting from flow, quality and meteorological variations. Emission rate variations can have significant effects on annoyance predictions, which is an important finding, as they are usually considered to be fixed and only meteorological variations are considered in predicting the odour footprint. Areas for further development of integrated odour modelling are discussed, in particular the search for improved links between analytical and sensory measurements, and a better understanding of dose/response relationships for odour annoyance.

  4. Cellular-based modeling of oscillatory dynamics in brain networks.

    PubMed

    Skinner, Frances K

    2012-08-01

    Oscillatory, population activities have long been known to occur in our brains during different behavioral states. We know that many different cell types exist and that they contribute in distinct ways to the generation of these activities. I review recent papers that involve cellular-based models of brain networks, most of which include theta, gamma and sharp wave-ripple activities. To help organize the modeling work, I present it from a perspective of three different types of cellular-based modeling: 'Generic', 'Biophysical' and 'Linking'. Cellular-based modeling is taken to encompass the four features of experiment, model development, theory/analyses, and model usage/computation. The three modeling types are shown to include these features and interactions in different ways.

  5. Do anesthetics harm the developing human brain? An integrative analysis of animal and human studies.

    PubMed

    Lin, Erica P; Lee, Jeong-Rim; Lee, Christopher S; Deng, Meng; Loepke, Andreas W

    Anesthetics that permit surgical procedures and stressful interventions have been found to cause structural brain abnormalities and functional impairment in immature animals, generating extensive concerns among clinicians, parents, and government regulators regarding the safe use of these drugs in young children. Critically important questions remain, such as the exact age at which the developing brain is most vulnerable to the effects of anesthetic exposure, whether a particular age exists beyond which anesthetics are devoid of long-term effects on the brain, and whether any specific exposure duration exists that does not lead to deleterious effects. Accordingly, the present analysis attempts to put the growing body of animal studies, which we identified to include >440 laboratory studies to date, into a translational context, by integrating the preclinical data on brain structure and function with clinical results attained from human neurocognitive studies, which currently exceed 30 studies. Our analysis demonstrated no clear exposure duration threshold below which no structural injury or subsequent cognitive abnormalities occurred. Animal data did not clearly identify a specific age beyond which anesthetic exposure did not cause any structural or functional abnormalities. Several potential mitigating strategies were found, however, no general anesthetic was identified that consistently lacked neurodegenerative properties and could be recommended over other anesthetics. It therefore is imperative, to expand efforts to devise safer anesthetic techniques and mitigating strategies, even before long-term alterations in brain development are unequivocally confirmed to occur in millions of young children undergoing anesthesia every year.

  6. Fitness, but not physical activity, is related to functional integrity of brain networks associated with aging.

    PubMed

    Voss, Michelle W; Weng, Timothy B; Burzynska, Agnieszka Z; Wong, Chelsea N; Cooke, Gillian E; Clark, Rachel; Fanning, Jason; Awick, Elizabeth; Gothe, Neha P; Olson, Erin A; McAuley, Edward; Kramer, Arthur F

    2016-05-01

    Greater physical activity and cardiorespiratory fitness are associated with reduced age-related cognitive decline and lower risk for dementia. However, significant gaps remain in the understanding of how physical activity and fitness protect the brain from adverse effects of brain aging. The primary goal of the current study was to empirically evaluate the independent relationships between physical activity and fitness with functional brain health among healthy older adults, as measured by the functional connectivity of cognitively and clinically relevant resting state networks. To build context for fitness and physical activity associations in older adults, we first demonstrate that young adults have greater within-network functional connectivity across a broad range of cortical association networks. Based on these results and previous research, we predicted that individual differences in fitness and physical activity would be most strongly associated with functional integrity of the networks most sensitive to aging. Consistent with this prediction, and extending on previous research, we showed that cardiorespiratory fitness has a positive relationship with functional connectivity of several cortical networks associated with age-related decline, and effects were strongest in the default mode network (DMN). Furthermore, our results suggest that the positive association of fitness with brain function can occur independent of habitual physical activity. Overall, our findings provide further support that cardiorespiratory fitness is an important factor in moderating the adverse effects of aging on cognitively and clinically relevant functional brain networks.

  7. A Higher Brain Circuit for Immediate Integration of Conflicting Sensory Information in Drosophila.

    PubMed

    Lewis, Laurence P C; Siju, K P; Aso, Yoshinori; Friedrich, Anja B; Bulteel, Alexander J B; Rubin, Gerald M; Grunwald Kadow, Ilona C

    2015-08-31

    Animals continuously evaluate sensory information to decide on their next action. Different sensory cues, however, often demand opposing behavioral responses. How does the brain process conflicting sensory information during decision making? Here, we show that flies use neural substrates attributed to odor learning and memory, including the mushroom body (MB), for immediate sensory integration and modulation of innate behavior. Drosophila melanogaster must integrate contradictory sensory information during feeding on fermenting fruit that releases both food odor and the innately aversive odor CO2. Here, using this framework, we examine the neural basis for this integration. We have identified a local circuit consisting of specific glutamatergic output and PAM dopaminergic input neurons with overlapping innervation in the MB-β'2 lobe region, which integrates food odor and suppresses innate avoidance. Activation of food odor-responsive dopaminergic neurons reduces innate avoidance mediated by CO2-responsive MB output neurons. We hypothesize that the MB, in addition to its long recognized role in learning and memory, serves as the insect's brain center for immediate sensory integration during instantaneous decision making.

  8. Localized Brain Volume and White Matter Integrity Alterations in Adolescent Anorexia Nervosa

    PubMed Central

    Frank, Guido K.W.; Shott, Megan E.; Hagman, Jennifer O.; Yang, Tony T.

    2014-01-01

    Objective The neurobiological underpinnings of anorexia nervosa (AN) are poorly understood. In this study we tested whether brain gray matter (GM) and white matter (WM) in adolescents with AN would show alterations comparable to adults. Method We used magnetic resonance imaging to study GM and WM volume, and diffusion tensor imaging to assess fractional anisotropy for WM integrity in 19 adolescents with AN and 22 controls. Results Individuals with AN showed greater left orbitofrontal, right insular, and bilateral temporal cortex GM, as well as temporal lobe WM volumes compared to controls. WM integrity in adolescents with AN was lower (lower fractional anisotropy) in fornix, posterior frontal, and parietal areas, but higher in anterior frontal, orbitofrontal, and temporal lobes. In individuals with AN, orbitofrontal GM volume correlated negatively with sweet taste pleasantness. An additional comparison of this study cohort with adult individuals with AN and healthy controls supported greater orbitofrontal cortex and insula volumes in AN across age groups. Conclusions This study indicates larger orbitofrontal and insular GM volumes, as well as lower fornix WM integrity in adolescents with AN, similar to adults. The pattern of larger anteroventral GM and WM volume as well as WM integrity, but lower WM integrity in posterior frontal and parietal regions may indicate that developmental factors such as GM pruning and WM growth could contribute to brain alterations in AN. The negative correlation between taste pleasantness and orbitofrontal cortex volume in individuals with AN could contribute to food avoidance in this disorder. PMID:24074473

  9. Host matrix metalloproteinases in cerebral malaria: new kids on the block against blood–brain barrier integrity?

    PubMed Central

    2014-01-01

    Cerebral malaria (CM) is a life-threatening complication of falciparum malaria, associated with high mortality rates, as well as neurological impairment in surviving patients. Despite disease severity, the etiology of CM remains elusive. Interestingly, although the Plasmodium parasite is sequestered in cerebral microvessels, it does not enter the brain parenchyma: so how does Plasmodium induce neuronal dysfunction? Several independent research groups have suggested a mechanism in which increased blood–brain barrier (BBB) permeability might allow toxic molecules from the parasite or the host to enter the brain. However, the reported severity of BBB damage in CM is variable depending on the model system, ranging from mild impairment to full BBB breakdown. Moreover, the factors responsible for increased BBB permeability are still unknown. Here we review the prevailing theories on CM pathophysiology and discuss new evidence from animal and human CM models implicating BBB damage. Finally, we will review the newly-described role of matrix metalloproteinases (MMPs) and BBB integrity. MMPs comprise a family of proteolytic enzymes involved in modulating inflammatory response, disrupting tight junctions, and degrading sub-endothelial basal lamina. As such, MMPs represent potential innovative drug targets for CM. PMID:24467887

  10. Integration of Dynamic Models in Range Operations

    NASA Technical Reports Server (NTRS)

    Bardina, Jorge; Thirumalainambi, Rajkumar

    2004-01-01

    This work addresses the various model interactions in real-time to make an efficient internet based decision making tool for Shuttle launch. The decision making tool depends on the launch commit criteria coupled with physical models. Dynamic interaction between a wide variety of simulation applications and techniques, embedded algorithms, and data visualizations are needed to exploit the full potential of modeling and simulation. This paper also discusses in depth details of web based 3-D graphics and applications to range safety. The advantages of this dynamic model integration are secure accessibility and distribution of real time information to other NASA centers.

  11. Fingernail Injuries and NASA's Integrated Medical Model

    NASA Technical Reports Server (NTRS)

    Kerstman, Eric; Butler, Doug

    2008-01-01

    The goal of space medicine is to optimize both crew health and performance. Currently, expert opinion is primarily relied upon for decision-making regarding medical equipment and supplies flown in space. Evidence-based decisions are preferred due to mass and volume limitations and the expense of space flight. The Integrated Medical Model (IMM) is an attempt to move us in that direction!

  12. Rethinking School Bullying: Towards an Integrated Model

    ERIC Educational Resources Information Center

    Dixon, Roz; Smith, Peter K.

    2011-01-01

    What would make anti-bullying initiatives more successful? This book offers a new approach to the problem of school bullying. The question of what constitutes a useful theory of bullying is considered and suggestions are made as to how priorities for future research might be identified. The integrated, systemic model of school bullying introduced…

  13. International Summit on Integrated Environmental Modeling

    EPA Science Inventory

    This report describes the International Summit on Integrated Environmental Modeling (IEM), held in Washington, DC 7th-9th December 2010. The meeting brought together 57 scientists and managers from leading US and European government and non-governmental organizations, universitie...

  14. Global fractional anisotropy and mean diffusivity together with segmented brain volumes assemble a predictive discriminant model for young and elderly healthy brains: a pilot study at 3T

    PubMed Central

    Garcia-Lazaro, Haydee Guadalupe; Becerra-Laparra, Ivonne; Cortez-Conradis, David; Roldan-Valadez, Ernesto

    2016-01-01

    Summary Several parameters of brain integrity can be derived from diffusion tensor imaging. These include fractional anisotropy (FA) and mean diffusivity (MD). Combination of these variables using multivariate analysis might result in a predictive model able to detect the structural changes of human brain aging. Our aim was to discriminate between young and older healthy brains by combining structural and volumetric variables from brain MRI: FA, MD, and white matter (WM), gray matter (GM) and cerebrospinal fluid (CSF) volumes. This was a cross-sectional study in 21 young (mean age, 25.71±3.04 years; range, 21–34 years) and 10 elderly (mean age, 70.20±4.02 years; range, 66–80 years) healthy volunteers. Multivariate discriminant analysis, with age as the dependent variable and WM, GM and CSF volumes, global FA and MD, and gender as the independent variables, was used to assemble a predictive model. The resulting model was able to differentiate between young and older brains: Wilks’ λ = 0.235, χ2 (6) = 37.603, p = .000001. Only global FA, WM volume and CSF volume significantly discriminated between groups. The total accuracy was 93.5%; the sensitivity, specificity and positive and negative predictive values were 91.30%, 100%, 100% and 80%, respectively. Global FA, WM volume and CSF volume are parameters that, when combined, reliably discriminate between young and older brains. A decrease in FA is the strongest predictor of membership of the older brain group, followed by an increase in WM and CSF volumes. Brain assessment using a predictive model might allow the follow-up of selected cases that deviate from normal aging. PMID:27027893

  15. Modeling integrated sensor/actuator functions in realistic environments

    NASA Astrophysics Data System (ADS)

    Kim, Jae-Wan; Varadan, Vasundara V.; Varadan, Vijay K.

    1993-07-01

    Smart materials are expected to adapt to their environment and provide a useful response to changes in the environment. Both the sensor and actuator functions with the appropriate feedback mechanism must be integrated and comprise the `brains' of the material. Piezoelectric ceramics have proved to be effective as both sensors and actuators for a wide variety of applications. Thus, realistic simulation models are needed that can predict the performance of smart materials that incorporate piezoceramics. The environment may include the structure on which the transducers are mounted, fluid medium and material damping. In all cases, the smart material should sense the change and make a useful response. A hybrid numerical method involving finite element modeling in the plate structure and transducer region and a plane wave representation in the fluid region is used. The simulation of the performance of smart materials are performed.

  16. Depression, Stress, and Anhedonia: Toward a Synthesis and Integrated Model

    PubMed Central

    Pizzagalli, Diego A.

    2014-01-01

    Depression is a significant public health problem, but its etiology and pathophysiology remain poorly understood. Such incomplete understanding likely arises from the fact that depression encompasses a heterogeneous set of disorders. To overcome these limitations, renewed interest in intermediate phenotypes (endophenotypes) has resurfaced, and anhedonia has emerged as one of the most promising endophenotypes of depression. Here, a heuristic model is presented postulating that anhedonia arises from dysfunctional interactions between stress and brain reward systems. To this end, we review and integrate three bodies of independent literature investigating the role of (1) anhedonia, (2) dopamine, and (3) stress in depression. In a fourth section, we summarize animal data indicating that stress negatively affect mesocorticolimbic dopaminergic pathways critically implicated in incentive motivation and reinforcement learning. In the last section, we provide a synthesis of these four literatures, present initial evidence consistent with our model, and discuss directions for future research. PMID:24471371

  17. Integrable extended van der Waals model

    NASA Astrophysics Data System (ADS)

    Giglio, Francesco; Landolfi, Giulio; Moro, Antonio

    2016-10-01

    Inspired by the recent developments in the study of the thermodynamics of van der Waals fluids via the theory of nonlinear conservation laws and the description of phase transitions in terms of classical (dissipative) shock waves, we propose a novel approach to the construction of multi-parameter generalisations of the van der Waals model. The theory of integrable nonlinear conservation laws still represents the inspiring framework. Starting from a macroscopic approach, a four parameter family of integrable extended van der Waals models is indeed constructed in such a way that the equation of state is a solution to an integrable nonlinear conservation law linearisable by a Cole-Hopf transformation. This family is further specified by the request that, in regime of high temperature, far from the critical region, the extended model reproduces asymptotically the standard van der Waals equation of state. We provide a detailed comparison of our extended model with two notable empirical models such as Peng-Robinson and Soave's modification of the Redlich-Kwong equations of state. We show that our extended van der Waals equation of state is compatible with both empirical models for a suitable choice of the free parameters and can be viewed as a master interpolating equation. The present approach also suggests that further generalisations can be obtained by including the class of dispersive and viscous-dispersive nonlinear conservation laws and could lead to a new type of thermodynamic phase transitions associated to nonclassical and dispersive shock waves.

  18. Identification of Differentially Expressed Genes through Integrated Study of Alzheimer’s Disease Affected Brain Regions

    PubMed Central

    Berretta, Regina; Moscato, Pablo

    2016-01-01

    Background Alzheimer’s disease (AD) is the most common form of dementia in older adults that damages the brain and results in impaired memory, thinking and behaviour. The identification of differentially expressed genes and related pathways among affected brain regions can provide more information on the mechanisms of AD. In the past decade, several studies have reported many genes that are associated with AD. This wealth of information has become difficult to follow and interpret as most of the results are conflicting. In that case, it is worth doing an integrated study of multiple datasets that helps to increase the total number of samples and the statistical power in detecting biomarkers. In this study, we present an integrated analysis of five different brain region datasets and introduce new genes that warrant further investigation. Methods The aim of our study is to apply a novel combinatorial optimisation based meta-analysis approach to identify differentially expressed genes that are associated to AD across brain regions. In this study, microarray gene expression data from 161 samples (74 non-demented controls, 87 AD) from the Entorhinal Cortex (EC), Hippocampus (HIP), Middle temporal gyrus (MTG), Posterior cingulate cortex (PC), Superior frontal gyrus (SFG) and visual cortex (VCX) brain regions were integrated and analysed using our method. The results are then compared to two popular meta-analysis methods, RankProd and GeneMeta, and to what can be obtained by analysing the individual datasets. Results We find genes related with AD that are consistent with existing studies, and new candidate genes not previously related with AD. Our study confirms the up-regualtion of INFAR2 and PTMA along with the down regulation of GPHN, RAB2A, PSMD14 and FGF. Novel genes PSMB2, WNK1, RPL15, SEMA4C, RWDD2A and LARGE are found to be differentially expressed across all brain regions. Further investigation on these genes may provide new insights into the development of AD

  19. Inferring brain-computational mechanisms with models of activity measurements

    PubMed Central

    Diedrichsen, Jörn

    2016-01-01

    High-resolution functional imaging is providing increasingly rich measurements of brain activity in animals and humans. A major challenge is to leverage such data to gain insight into the brain's computational mechanisms. The first step is to define candidate brain-computational models (BCMs) that can perform the behavioural task in question. We would then like to infer which of the candidate BCMs best accounts for measured brain-activity data. Here we describe a method that complements each BCM by a measurement model (MM), which simulates the way the brain-activity measurements reflect neuronal activity (e.g. local averaging in functional magnetic resonance imaging (fMRI) voxels or sparse sampling in array recordings). The resulting generative model (BCM-MM) produces simulated measurements. To avoid having to fit the MM to predict each individual measurement channel of the brain-activity data, we compare the measured and predicted data at the level of summary statistics. We describe a novel particular implementation of this approach, called probabilistic representational similarity analysis (pRSA) with MMs, which uses representational dissimilarity matrices (RDMs) as the summary statistics. We validate this method by simulations of fMRI measurements (locally averaging voxels) based on a deep convolutional neural network for visual object recognition. Results indicate that the way the measurements sample the activity patterns strongly affects the apparent representational dissimilarities. However, modelling of the measurement process can account for these effects, and different BCMs remain distinguishable even under substantial noise. The pRSA method enables us to perform Bayesian inference on the set of BCMs and to recognize the data-generating model in each case. This article is part of the themed issue ‘Interpreting BOLD: a dialogue between cognitive and cellular neuroscience’. PMID:27574316

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

    PubMed Central

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

    2014-01-01

    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. PMID:25180309

  1. A hybrid model for the neural representation of complex mental processing in the human brain.

    PubMed

    Fehr, Thorsten

    2013-04-01

    In the present conceptual review several theoretical and empirical sources of information were integrated, and a hybrid model of the neural representation of complex mental processing in the human brain was proposed. Based on empirical evidence for strategy-related and inter-individually different task-related brain activation networks, and further based on empirical evidence for a remarkable overlap of fronto-parietal activation networks across different complex mental processes, it was concluded by the author that there might be innate and modular organized neuro-developmental starting regions, for example, in intra-parietal, and both medial and middle frontal brain regions, from which the neural organization of different kinds of complex mental processes emerge differently during individually shaped learning histories. Thus, the here proposed model provides a hybrid of both massive modular and holistic concepts of idiosyncratic brain physiological elaboration of complex mental processing. It is further concluded that 3-D information, obtained by respective methodological approaches, are not appropriate to identify the non-linear spatio-temporal dynamics of complex mental process-related brain activity in a sufficient way. How different participating network parts communicate with each other seems to be an indispensable aspect, which has to be considered in particular to improve our understanding of the neural organization of complex cognition.

  2. Animal Models of Brain Maldevelopment Induced by Cycad Plant Genotoxins

    PubMed Central

    Kisby, Glen E.; Moore, Holly; Spencer, Peter S.

    2014-01-01

    Cycads are long-lived tropical and subtropical plants that contain azoxyglycosides (e.g., cycasin, macrozamin) and neurotoxic amino acids (notably β-N-methylamino-L-alanine L-BMAA), toxins that have been implicated in the etiology of a disappearing neurodegenerative disease, amyotrophic lateral sclerosis and parkinsonism-dementia complex that has been present in high incidence among three genetically distinct populations in the western Pacific. The neuropathology of amyotrophic lateral sclerosis/parkinsonism-dementia complex includes features suggestive of brain maldevelopment, an experimentally proven property of cycasin attributable to the genotoxic action of its aglycone methylazoxymethanol (MAM). This property of MAM has been exploited by neurobiologists as a tool to study perturbations of brain development. Depending on the neurodevelopmental stage, MAM can induce features in laboratory animals that model certain characteristics of epilepsy, schizophrenia, or ataxia. Studies in DNA repair-deficient mice show that MAM perturbs brain development through a DNA damage-mediated mechanism. The brain DNA lesions produced by systemic MAM appear to modulate the expression of genes that regulate neurodevelopment and contribute to neurodegeneration. Epigenetic changes (histone lysine methylation) have also been detected in the underdeveloped brain after MAM administration. The DNA damage and epigenetic changes produced by MAM and, perhaps by chemically related substances (e.g., nitrosamines, nitrosoureas, hydrazines), might be an important mechanism by which early-life exposure to genotoxicants can induce long-term brain dysfunction. PMID:24339036

  3. Animal models of focal brain ischemia

    PubMed Central

    2009-01-01

    Stroke is a leading cause of disability and death in many countries. Understanding the pathophysiology of ischemic injury and developing therapies is an important endeavor that requires much additional research. Animal stroke models provide an important mechanism for these activities. A large number of stroke models have been developed and are currently used in laboratories around the world. These models are overviewed as are approaches for measuring infarct size and functional outcome. PMID:20150985

  4. Multifactorial causal model of brain (dis)organization and therapeutic intervention: Application to Alzheimer's disease.

    PubMed

    Iturria-Medina, Yasser; Carbonell, Félix M; Sotero, Roberto C; Chouinard-Decorte, Francois; Evans, Alan C

    2017-02-28

    Generative models focused on multifactorial causal mechanisms in brain disorders are scarce and generally based on limited data. Despite the biological importance of the multiple interacting processes, their effects remain poorly characterized from an integrative analytic perspective. Here, we propose a spatiotemporal multifactorial causal model (MCM) of brain (dis)organization and therapeutic intervention that accounts for local causal interactions, effects propagation via physical brain networks, cognitive alterations, and identification of optimum therapeutic interventions. In this article, we focus on describing the model and applying it at the population-based level for studying late onset Alzheimer's disease (LOAD). By interrelating six different neuroimaging modalities and cognitive measurements, this model accurately predicts spatiotemporal alterations in brain amyloid-β (Aβ) burden, glucose metabolism, vascular flow, resting state functional activity, structural properties, and cognitive integrity. The results suggest that a vascular dysregulation may be the most-likely initial pathologic event leading to LOAD. Nevertheless, they also suggest that LOAD it is not caused by a unique dominant biological factor (e.g. vascular or Aβ) but by the complex interplay among multiple relevant direct interactions. Furthermore, using theoretical control analysis of the identified population-based multifactorial causal network, we show the crucial advantage of using combinatorial over single-target treatments, explain why one-target Aβ based therapies might fail to improve clinical outcomes, and propose an efficiency ranking of possible LOAD interventions. Although still requiring further validation at the individual level, this work presents the first analytic framework for dynamic multifactorial brain (dis)organization that may explain both the pathologic evolution of progressive neurological disorders and operationalize the influence of multiple interventional

  5. High-Throughput Screening for Identification of Blood-Brain Barrier Integrity Enhancers: A Drug Repurposing Opportunity to Rectify Vascular Amyloid Toxicity.

    PubMed

    Qosa, Hisham; Mohamed, Loqman A; Al Rihani, Sweilem B; Batarseh, Yazan S; Duong, Quoc-Viet; Keller, Jeffrey N; Kaddoumi, Amal

    2016-07-06

    The blood-brain barrier (BBB) is a dynamic interface that maintains brain homeostasis and protects it from free entry of chemicals, toxins, and drugs. The barrier function of the BBB is maintained mainly by capillary endothelial cells that physically separate brain from blood. Several neurological diseases, such as Alzheimer's disease (AD), are known to disrupt BBB integrity. In this study, a high-throughput screening (HTS) was developed to identify drugs that rectify/protect BBB integrity from vascular amyloid toxicity associated with AD progression. Assessing Lucifer Yellow permeation across in-vitro BBB model composed from mouse brain endothelial cells (bEnd3) grown on 96-well plate inserts was used to screen 1280 compounds of Sigma LOPAC®1280 library for modulators of bEnd3 monolayer integrity. HTS identified 62 compounds as disruptors, and 50 compounds as enhancers of the endothelial barrier integrity. From these 50 enhancers, 7 FDA approved drugs were identified with EC50 values ranging from 0.76-4.56 μM. Of these 7 drugs, 5 were able to protect bEnd3-based BBB model integrity against amyloid toxicity. Furthermore, to test the translational potential to humans, the 7 drugs were tested for their ability to rectify the disruptive effect of Aβ in the human endothelial cell line hCMEC/D3. Only 3 (etodolac, granisetron, and beclomethasone) out of the 5 effective drugs in the bEnd3-based BBB model demonstrated a promising effect to protect the hCMEC/D3-based BBB model integrity. These drugs are compelling candidates for repurposing as therapeutic agents that could rectify dysfunctional BBB associated with AD.

  6. Transcranial current brain stimulation (tCS): models and technologies.

    PubMed

    Ruffini, Giulio; Wendling, Fabrice; Merlet, Isabelle; Molaee-Ardekani, Behnam; Mekonnen, Abeye; Salvador, Ricardo; Soria-Frisch, Aureli; Grau, Carles; Dunne, Stephen; Miranda, Pedro C

    2013-05-01

    In this paper, we provide a broad overview of models and technologies pertaining to transcranial current brain stimulation (tCS), a family of related noninvasive techniques including direct current (tDCS), alternating current (tACS), and random noise current stimulation (tRNS). These techniques are based on the delivery of weak currents through the scalp (with electrode current intensity to area ratios of about 0.3-5 A/m2) at low frequencies (typically < 1 kHz) resulting in weak electric fields in the brain (with amplitudes of about 0.2-2 V/m). Here we review the biophysics and simulation of noninvasive, current-controlled generation of electric fields in the human brain and the models for the interaction of these electric fields with neurons, including a survey of in vitro and in vivo related studies. Finally, we outline directions for future fundamental and technological research.

  7. FACETS -- Infrastructure for Integrated Fusion Modeling

    NASA Astrophysics Data System (ADS)

    Shasharina, Svetlana; Cary, John; Carlsson, Johan; Hakim, Ammar; Kruger, Scott; Miah, Mahmood; Pletzer, Alexander; Vadlamani, Srinath; Wade-Stein, David; Balay, Satish; McInnes, Lois; Zhang, Hong; Candy, Jeff; Fahey, Mark; Cohen, Ron; Epperly, Tom; Rognlien, Tom; Estep, Don; Pankin, Alexei; Malony, Allen; Morris, Alan; Shende, Sameer; Indireshkumar, Keshavamurthy; McCune, Douglas; Pigarov, Alexander

    2009-11-01

    It is desirable that an infrastructure for integrated fusion modeling has support for: legacy and new components used interchangeably; consistent management of components lifecycle; allocating parallel resources consistent with the nature of participating components and the problem scope; components written in multiple programming languages; composition of sequentially and concurrently executing components respecting dependencies; tight and loose coupling of components; testing and validation of separate and integrated components; and use of multiple platforms from desktops to LCFs. In this poster we will describe the status of the FACETS with respect to these features.

  8. Paradox of integration-A computational model

    NASA Astrophysics Data System (ADS)

    Krawczyk, Małgorzata J.; Kułakowski, Krzysztof

    2017-02-01

    The paradoxical aspect of integration of a social group has been highlighted by Blau (1964). During the integration process, the group members simultaneously compete for social status and play the role of the audience. Here we show that when the competition prevails over the desire of approval, a sharp transition breaks all friendly relations. However, as was described by Blau, people with high status are inclined to bother more with acceptance of others; this is achieved by praising others and revealing her/his own weak points. In our model, this action smooths the transition and improves interpersonal relations.

  9. Computational modeling of an endovascular approach to deep brain stimulation

    NASA Astrophysics Data System (ADS)

    Teplitzky, Benjamin A.; Connolly, Allison T.; Bajwa, Jawad A.; Johnson, Matthew D.

    2014-04-01

    Objective. Deep brain stimulation (DBS) therapy currently relies on a transcranial neurosurgical technique to implant one or more electrode leads into the brain parenchyma. In this study, we used computational modeling to investigate the feasibility of using an endovascular approach to target DBS therapy. Approach. Image-based anatomical reconstructions of the human brain and vasculature were used to identify 17 established and hypothesized anatomical targets of DBS, of which five were found adjacent to a vein or artery with intraluminal diameter ≥1 mm. Two of these targets, the fornix and subgenual cingulate white matter (SgCwm) tracts, were further investigated using a computational modeling framework that combined segmented volumes of the vascularized brain, finite element models of the tissue voltage during DBS, and multi-compartment axon models to predict the direct electrophysiological effects of endovascular DBS. Main results. The models showed that: (1) a ring-electrode conforming to the vessel wall was more efficient at neural activation than a guidewire design, (2) increasing the length of a ring-electrode had minimal effect on neural activation thresholds, (3) large variability in neural activation occurred with suboptimal placement of a ring-electrode along the targeted vessel, and (4) activation thresholds for the fornix and SgCwm tracts were comparable for endovascular and stereotactic DBS, though endovascular DBS was able to produce significantly larger contralateral activation for a unilateral implantation. Significance. Together, these results suggest that endovascular DBS can serve as a complementary approach to stereotactic DBS in select cases.

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

    PubMed

    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.

  11. Integrating sensorimotor systems in a robot model of cricket behavior

    NASA Astrophysics Data System (ADS)

    Webb, Barbara H.; Harrison, Reid R.

    2000-10-01

    The mechanisms by which animals manage sensorimotor integration and coordination of different behaviors can be investigated in robot models. In previous work the first author has build a robot that localizes sound based on close modeling of the auditory and neural system in the cricket. It is known that the cricket combines its response to sound with other sensorimotor activities such as an optomotor reflex and reactions to mechanical stimulation for the antennae and cerci. Behavioral evidence suggests some ways these behaviors may be integrated. We have tested the addition of an optomotor response, using an analog VLSI circuit developed by the second author, to the sound localizing behavior and have shown that it can, as in the cricket, improve the directness of the robot's path to sound. In particular it substantially improves behavior when the robot is subject to a motor disturbance. Our aim is to better understand how the insect brain functions in controlling complex combinations of behavior, with the hope that this will also suggest novel mechanisms for sensory integration on robots.

  12. Genetics of ageing-related changes in brain white matter integrity - a review.

    PubMed

    Kanchibhotla, Sri C; Mather, Karen A; Wen, Wei; Schofield, Peter R; Kwok, John B J; Sachdev, Perminder S

    2013-01-01

    White matter (WM) plays a vital role in the efficient transfer of information between grey matter regions. Modern imaging techniques such as diffusion tensor imaging (DTI) have enabled the examination of WM microstructural changes across the lifespan, but there is limited knowledge about the role genetics plays in the pattern and aetiology of age-related WM microstructural changes. Family and twin studies suggest that the heritability of WM integrity measures changes over the lifespan, with the common DTI measure, fractional anisotropy (FA), showing moderate to high heritability in adults. However, few heritability studies have been undertaken in older adults. Linkage studies in middle-aged adults suggest that specific regions on chromosomes 3 and 15 may harbour genetic variants for WM integrity. A number of studies have investigated candidate genes, with the APOE ɛ4 polymorphism being the most frequently studied. Although these candidate gene studies suggest associations of particular genes with WM integrity measures in some specific brain regions, the findings remain inconsistent due to differences in their methodologies, samples and the outcome measures used. The APOE ɛ4 allele has been associated with decreased WM integrity (FA) in the cingulum, corpus callosum and parahippocampal gyrus. Only one genome-wide association study of global WM integrity measures in older adults has been published, and reported suggestive single nucleotide polymorphisms await replication. Overall, genetic age-related WM integrity studies are lacking and a concerted effort to examine the genetic determinants of age-related decline in WM integrity is clearly needed to improve our understanding of the ageing brain.

  13. Cellular immortality in brain tumours: an integration of the cancer stem cell paradigm.

    PubMed

    Rahman, Ruman; Heath, Rachel; Grundy, Richard

    2009-04-01

    Brain tumours are a diverse group of neoplasms that continue to present a formidable challenge in our attempt to achieve curable intervention. Our conceptual framework of human brain cancer has been redrawn in the current decade. There is a gathering acceptance that brain tumour formation is a phenotypic outcome of dysregulated neurogenesis, with tumours viewed as abnormally differentiated neural tissue. In relation, there is accumulating evidence that brain tumours, similar to leukaemia and many solid tumours, are organized as a developmental hierarchy which is maintained by a small fraction of cells endowed with many shared properties of tissue stem cells. Proof that neurogenesis persists throughout adult life, compliments this concept. Although the cancer cell of origin is unclear, the proliferative zones that harbour stem cells in the embryonic, post-natal and adult brain are attractive candidates within which tumour-initiation may ensue. Dysregulated, unlimited proliferation and an ability to bypass senescence are acquired capabilities of cancerous cells. These abilities in part require the establishment of a telomere maintenance mechanism for counteracting the shortening of chromosomal termini. A strategy based upon the synthesis of telomeric repeat sequences by the ribonucleoprotein telomerase, is prevalent in approximately 90% of human tumours studied, including the majority of brain tumours. This review will provide a developmental perspective with respect to normal (neurogenesis) and aberrant (tumourigenesis) cellular turnover, differentiation and function. Within this context our current knowledge of brain tumour telomere/telomerase biology will be discussed with respect to both its developmental and therapeutic relevance to the hierarchical model of brain tumourigenesis presented by the cancer stem cell paradigm.

  14. Multigrid Nonlocal Gaussian Mixture Model for Segmentation of Brain Tissues in Magnetic Resonance Images.

    PubMed

    Chen, Yunjie; Zhan, Tianming; Zhang, Ji; Wang, Hongyuan

    2016-01-01

    We propose a novel segmentation method based on regional and nonlocal information to overcome the impact of image intensity inhomogeneities and noise in human brain magnetic resonance images. With the consideration of the spatial distribution of different tissues in brain images, our method does not need preestimation or precorrection procedures for intensity inhomogeneities and noise. A nonlocal information based Gaussian mixture model (NGMM) is proposed to reduce the effect of noise. To reduce the effect of intensity inhomogeneity, the multigrid nonlocal Gaussian mixture model (MNGMM) is proposed to segment brain MR images in each nonoverlapping multigrid generated by using a new multigrid generation method. Therefore the proposed model can simultaneously overcome the impact of noise and intensity inhomogeneity and automatically classify 2D and 3D MR data into tissues of white matter, gray matter, and cerebral spinal fluid. To maintain the statistical reliability and spatial continuity of the segmentation, a fusion strategy is adopted to integrate the clustering results from different grid. The experiments on synthetic and clinical brain MR images demonstrate the superior performance of the proposed model comparing with several state-of-the-art algorithms.

  15. An overview of the model integration process: From pre-integration assessment to testing

    EPA Science Inventory

    Integration of models requires linking models which can be developed using different tools, methodologies, and assumptions. We performed a literature review with the aim of improving our understanding of model integration process, and also presenting better strategies for buildin...

  16. Brain mechanisms in religion and spirituality: An integrative predictive processing framework.

    PubMed

    van Elk, Michiel; Aleman, André

    2017-02-01

    We present the theory of predictive processing as a unifying framework to account for the neurocognitive basis of religion and spirituality. Our model is substantiated by discussing four different brain mechanisms that play a key role in religion and spirituality: temporal brain areas are associated with religious visions and ecstatic experiences; multisensory brain areas and the default mode network are involved in self-transcendent experiences; the Theory of Mind-network is associated with prayer experiences and over attribution of intentionality; top-down mechanisms instantiated in the anterior cingulate cortex and the medial prefrontal cortex could be involved in acquiring and maintaining intuitive supernatural beliefs. We compare the predictive processing model with two-systems accounts of religion and spirituality, by highlighting the central role of prediction error monitoring. We conclude by presenting novel predictions for future research and by discussing the philosophical and theological implications of neuroscientific research on religion and spirituality.

  17. Separate Brain Circuits Support Integrative and Semantic Priming in the Human Language System.

    PubMed

    Feng, Gangyi; Chen, Qi; Zhu, Zude; Wang, Suiping

    2016-07-01

    Semantic priming is a crucial phenomenon to study the organization of semantic memory. A novel type of priming effect, integrative priming, has been identified behaviorally, whereby a prime word facilitates recognition of a target word when the 2 concepts can be combined to form a unitary representation. We used both functional and anatomical imaging approaches to investigate the neural substrates supporting such integrative priming, and compare them with those in semantic priming. Similar behavioral priming effects for both semantic (Bread-Cake) and integrative conditions (Cherry-Cake) were observed when compared with an unrelated condition. However, a clearly dissociated brain response was observed between these 2 types of priming. The semantic-priming effect was localized to the posterior superior temporal and middle temporal gyrus. In contrast, the integrative-priming effect localized to the left anterior inferior frontal gyrus and left anterior temporal cortices. Furthermore, fiber tractography showed that the integrative-priming regions were connected via uncinate fasciculus fiber bundle forming an integrative circuit, whereas the semantic-priming regions connected to the posterior frontal cortex via separated pathways. The results point to dissociable neural pathways underlying the 2 distinct types of priming, illuminating the neural circuitry organization of semantic representation and integration.

  18. Markers for blood-brain barrier integrity: how appropriate is Evans blue in the twenty-first century and what are the alternatives?

    PubMed Central

    Saunders, Norman R.; Dziegielewska, Katarzyna M.; Møllgård, Kjeld; Habgood, Mark D.

    2015-01-01

    In recent years there has been a resurgence of interest in brain barriers and various roles their intrinsic mechanisms may play in neurological disorders. Such studies require suitable models and markers to demonstrate integrity and functional changes at the interfaces between blood, brain, and cerebrospinal fluid. Studies of brain barrier mechanisms and measurements of plasma volume using dyes have a long-standing history, dating back to the late nineteenth-century. Their use in blood-brain barrier studies continues in spite of their known serious limitations in in vivo applications. These were well known when first introduced, but seem to have been forgotten since. Understanding these limitations is important because Evans blue is still the most commonly used marker of brain barrier integrity and those using it seem oblivious to problems arising from its in vivo application. The introduction of HRP in the mid twentieth-century was an important advance because its reaction product can be visualized at the electron microscopical level, but it also has limitations. Advantages and disadvantages of these markers will be discussed together with a critical evaluation of alternative approaches. There is no single marker suitable for all purposes. A combination of different sized, visualizable dextrans and radiolabeled molecules currently seems to be the most appropriate approach for qualitative and quantitative assessment of barrier integrity. PMID:26578854

  19. Markers for blood-brain barrier integrity: how appropriate is Evans blue in the twenty-first century and what are the alternatives?

    PubMed

    Saunders, Norman R; Dziegielewska, Katarzyna M; Møllgård, Kjeld; Habgood, Mark D

    2015-01-01

    In recent years there has been a resurgence of interest in brain barriers and various roles their intrinsic mechanisms may play in neurological disorders. Such studies require suitable models and markers to demonstrate integrity and functional changes at the interfaces between blood, brain, and cerebrospinal fluid. Studies of brain barrier mechanisms and measurements of plasma volume using dyes have a long-standing history, dating back to the late nineteenth-century. Their use in blood-brain barrier studies continues in spite of their known serious limitations in in vivo applications. These were well known when first introduced, but seem to have been forgotten since. Understanding these limitations is important because Evans blue is still the most commonly used marker of brain barrier integrity and those using it seem oblivious to problems arising from its in vivo application. The introduction of HRP in the mid twentieth-century was an important advance because its reaction product can be visualized at the electron microscopical level, but it also has limitations. Advantages and disadvantages of these markers will be discussed together with a critical evaluation of alternative approaches. There is no single marker suitable for all purposes. A combination of different sized, visualizable dextrans and radiolabeled molecules currently seems to be the most appropriate approach for qualitative and quantitative assessment of barrier integrity.

  20. A mathematical model of blood, cerebrospinal fluid and brain dynamics.

    PubMed

    Linninger, Andreas A; Xenos, Michalis; Sweetman, Brian; Ponkshe, Sukruti; Guo, Xiaodong; Penn, Richard

    2009-12-01

    Using first principles of fluid and solid mechanics a comprehensive model of human intracranial dynamics is proposed. Blood, cerebrospinal fluid (CSF) and brain parenchyma as well as the spinal canal are included. The compartmental model predicts intracranial pressure gradients, blood and CSF flows and displacements in normal and pathological conditions like communicating hydrocephalus. The system of differential equations of first principles conservation balances is discretized and solved numerically. Fluid-solid interactions of the brain parenchyma with cerebral blood and CSF are calculated. The model provides the transitions from normal dynamics to the diseased state during the onset of communicating hydrocephalus. Predicted results were compared with physiological data from Cine phase-contrast magnetic resonance imaging to verify the dynamic model. Bolus injections into the CSF are simulated in the model and found to agree with clinical measurements.

  1. The role of pericytic laminin in blood brain barrier integrity maintenance

    PubMed Central

    Gautam, Jyoti; Zhang, Xuanming; Yao, Yao

    2016-01-01

    Laminin, a major component of the basement membrane, plays an important role in blood brain barrier regulation. At the neurovascular unit, brain endothelial cells, astrocytes, and pericytes synthesize and deposit different laminin isoforms into the basement membrane. It has been shown that laminin α4 (endothelial laminin) regulates vascular integrity at embryonic/neonatal stage, while astrocytic laminin maintains vascular integrity in adulthood. Here, we investigate the function of pericyte-derived laminin in vascular integrity. Using a conditional knockout mouse line, we report that loss of pericytic laminin leads to hydrocephalus and BBB breakdown in a small percentage (10.7%) of the mutants. Interestingly, BBB disruption always goes hand-in-hand with hydrocephalus in these mutants, and neither symptom is observed in the rest 89.3% of the mutants. Further mechanistic studies show that reduced tight junction proteins, diminished AQP4 expression, and decreased pericyte coverage are responsible for the BBB disruption. Together, these data suggest that pericyte-derived laminin is involved in the maintenance of BBB integrity and regulation of ventricular size/development. PMID:27808256

  2. A statistical model for brain networks inferred from large-scale electrophysiological signals.

    PubMed

    Obando, Catalina; De Vico Fallani, Fabrizio

    2017-03-01

    Network science has been extensively developed to characterize the structural properties of complex systems, including brain networks inferred from neuroimaging data. As a result of the inference process, networks estimated from experimentally obtained biological data represent one instance of a larger number of realizations with similar intrinsic topology. A modelling approach is therefore needed to support statistical inference on the bottom-up local connectivity mechanisms influencing the formation of the estimated brain networks. Here, we adopted a statistical model based on exponential random graph models (ERGMs) to reproduce brain networks, or connectomes, estimated by spectral coherence between high-density electroencephalographic (EEG) signals. ERGMs are made up by different local graph metrics, whereas the parameters weight the respective contribution in explaining the observed network. We validated this approach in a dataset of N = 108 healthy subjects during eyes-open (EO) and eyes-closed (EC) resting-state conditions. Results showed that the tendency to form triangles and stars, reflecting clustering and node centrality, better explained the global properties of the EEG connectomes than other combinations of graph metrics. In particular, the synthetic networks generated by this model configuration replicated the characteristic differences found in real brain networks, with EO eliciting significantly higher segregation in the alpha frequency band (8-13 Hz) than EC. Furthermore, the fitted ERGM parameter values provided complementary information showing that clustering connections are significantly more represented from EC to EO in the alpha range, but also in the beta band (14-29 Hz), which is known to play a crucial role in cortical processing of visual input and externally oriented attention. Taken together, these findings support the current view of the functional segregation and integration of the brain in terms of modules and hubs, and provide a

  3. Experimental model for civilian ballistic brain injury biomechanics quantification.

    PubMed

    Zhang, Jiangyue; Yoganandan, Narayan; Pintar, Frank A; Guan, Yabo; Gennarelli, Thomas A

    2007-01-01

    Biomechanical quantification of projectile penetration using experimental head models can enhance the understanding of civilian ballistic brain injury and advance treatment. Two of the most commonly used handgun projectiles (25-cal, 275 m/s and 9 mm, 395 m/s) were discharged to spherical head models with gelatin and Sylgard simulants. Four ballistic pressure transducers recorded temporal pressure distributions at 308kHz, and temporal cavity dynamics were captured at 20,000 frames/second (fps) using high-speed digital video images. Pressures ranged from 644.6 to -92.8 kPa. Entry pressures in gelatin models were higher than exit pressures, whereas in Sylgard models entry pressures were lower or equivalent to exit pressures. Gelatin responded with brittle-type failure, while Sylgard demonstrated a ductile pattern through formation of micro-bubbles along projectile path. Temporary cavities in Sylgard models were 1.5-2x larger than gelatin models. Pressures in Sylgard models were more sensitive to projectile velocity and diameter increase, indicating Sylgard was more rate sensitive than gelatin. Based on failure patterns and brain tissue rate-sensitive characteristics, Sylgard was found to be an appropriate simulant. Compared with spherical projectile data, full-metal jacket (FMJ) projectiles produced different temporary cavity and pressures, demonstrating shape effects. Models using Sylgard gel and FMJ projectiles are appropriate to enhance understanding and mechanisms of ballistic brain injury.

  4. Directions for Mind, Brain, and Education: Methods, Models, and Morality

    ERIC Educational Resources Information Center

    Stein, Zachary; Fischer, Kurt W.

    2011-01-01

    In this article we frame a set of important issues in the emerging field of Mind, Brain, and Education in terms of three broad headings: methods, models, and morality. Under the heading of methods we suggest that the need for synthesis across scientific and practical disciplines entails the pursuit of usable knowledge via a catalytic symbiosis…

  5. Integrated UV fluorescence/DIAL model

    SciTech Connect

    Jefferson, K.J.

    1994-06-01

    Current SNL CALIOPE modeling efforts have produced an initial model that addresses DIAL issues of wavelength, hardware design parameters, range evaluation, etc. Although this model is producing valuable results and will be used to support the planning and evaluations necessary for the first ground field experiment, it is expected to have limitations with the complex science issues that affect the CALIOPE program. In particular, the multi-dimensional effects of atmospheric turbulence, plume dynamics, speckle, etc., may be significant issues and must be evaluated in detail as the program moves to the detection of liquids and solids, longer ranges, and elevated platform environments. The goal of the integrated UV fluorescence/DIAL modeling effort is to build upon the knowledge obtained in developing and exercising the initial model to adequately support the future activities of this program. This paper will address the development of the integrated UV model, issues and limiting assumptions that may be needed in order to address the-complex phenomena involved, limits of expected performance, and the potential use of this model.

  6. CTBT Integrated Verification System Evaluation Model

    SciTech Connect

    Edenburn, M.W.; Bunting, M.L.; Payne, A.C. Jr.

    1997-10-01

    Sandia National Laboratories has developed a computer based model called IVSEM (Integrated Verification System Evaluation Model) to estimate the performance of a nuclear detonation monitoring system. The IVSEM project was initiated in June 1994, by Sandia`s Monitoring Systems and Technology Center and has been funded by the US Department of Energy`s Office of Nonproliferation and National Security (DOE/NN). IVSEM is a simple, top-level, modeling tool which estimates the performance of a Comprehensive Nuclear Test Ban Treaty (CTBT) monitoring system and can help explore the impact of various sensor system concepts and technology advancements on CTBT monitoring. One of IVSEM`s unique features is that it integrates results from the various CTBT sensor technologies (seismic, infrasound, radionuclide, and hydroacoustic) and allows the user to investigate synergy among the technologies. Specifically, IVSEM estimates the detection effectiveness (probability of detection) and location accuracy of the integrated system and of each technology subsystem individually. The model attempts to accurately estimate the monitoring system`s performance at medium interfaces (air-land, air-water) and for some evasive testing methods such as seismic decoupling. This report describes version 1.2 of IVSEM.

  7. Effects of exercise on brain functions in diabetic animal models.

    PubMed

    Yi, Sun Shin

    2015-05-15

    Human life span has dramatically increased over several decades, and the quality of life has been considered to be equally important. However, diabetes mellitus (DM) characterized by problems related to insulin secretion and recognition has become a serious health problem in recent years that threatens human health by causing decline in brain functions and finally leading to neurodegenerative diseases. Exercise is recognized as an effective therapy for DM without medication administration. Exercise studies using experimental animals are a suitable option to overcome this drawback, and animal studies have improved continuously according to the needs of the experimenters. Since brain health is the most significant factor in human life, it is very important to assess brain functions according to the different exercise conditions using experimental animal models. Generally, there are two types of DM; insulin-dependent type 1 DM and an insulin-independent type 2 DM (T2DM); however, the author will mostly discuss brain functions in T2DM animal models in this review. Additionally, many physiopathologic alterations are caused in the brain by DM such as increased adiposity, inflammation, hormonal dysregulation, uncontrolled hyperphagia, insulin and leptin resistance, and dysregulation of neurotransmitters and declined neurogenesis in the hippocampus and we describe how exercise corrects these alterations in animal models. The results of changes in the brain environment differ according to voluntary, involuntary running exercises and resistance exercise, and gender in the animal studies. These factors have been mentioned in this review, and this review will be a good reference for studying how exercise can be used with therapy for treating DM.

  8. The effects of hyperbaric air and hyperbaric oxygen on blood-brain barrier integrity in rats.

    PubMed

    Cevik, Nihal Gunes; Orhan, Nurcan; Yilmaz, Canan Ugur; Arican, Nadir; Ahishali, Bulent; Kucuk, Mutlu; Kaya, Mehmet; Toklu, Akin Savas

    2013-09-19

    Hyperbaric oxygen (HBO) treatment yields conflicting results on blood-brain barrier (BBB) integrity under various pathological conditions and the effects of HBO on healthy brain is poorly understood. In this experimental study, the effects of HBO on BBB integrity were investigated in comparison with hyperbaric air (HBA) in intact rats. Four sessions of HBA or HBO were applied to intact rats in 24h. BBB integrity was functionally and structurally evaluated by determining extravasation of Evans blue (EB) dye and horseradish peroxidase (HRP) tracers. In immunohistochemical evaluation, relative staining intensity for occludin, a tight junction (TJ) protein, and aquaporin 4 (AQP4), a water-channel protein, was detected in the barrier type of microvessels of brain by image analysis. BBB permeability to EB dye significantly increased in animals in HBO treatment group compared to those in HBA and control groups (p<0.05). The immunoreactivity of occludin, a tight junction protein, remained essentially unaltered in capillaries of hippocampus in all groups. In animals exposed to HBO, AQP4 immunoreactivity significantly increased in parietal cortex compared to those in HBA and control groups (p<0.01). Ultrastructurally, frequent vesicles containing HRP reaction products were observed in capillary endothelial cells in cerebral cortex and hippocampus of rats subjected to both HBA and HBO. Our results indicate that the HBO administration to intact rats increased BBB permeability to both EB and HRP while HBA increased only HRP extravasation in these animals. The results of this study suggest that HBA also impairs the BBB integrity in intact rats as well as HBO.

  9. Computational models to understand decision making and pattern recognition in the insect brain.

    PubMed

    Mosqueiro, Thiago S; Huerta, Ramón

    2014-12-01

    Odor stimuli reaching olfactory systems of mammals and insects are characterized by remarkable non-stationary and noisy time series. Their brains have evolved to discriminate subtle changes in odor mixtures and find meaningful variations in complex spatio-temporal patterns. Insects with small brains can effectively solve two computational tasks: identify the presence of an odor type and estimate the concentration levels of the odor. Understanding the learning and decision making processes in the insect brain can not only help us to uncover general principles of information processing in the brain, but it can also provide key insights to artificial chemical sensing. Both olfactory learning and memory are dominantly organized in the Antennal Lobe (AL) and the Mushroom Bodies (MBs). Current computational models yet fail to deliver an integrated picture of the joint computational roles of the AL and MBs. This review intends to provide an integrative overview of the computational literature analyzed in the context of the problem of classification (odor discrimination) and regression (odor concentration estimation), particularly identifying key computational ingredients necessary to solve pattern recognition.

  10. The brain's spontaneous activity and its psychopathological symptoms - "Spatiotemporal binding and integration".

    PubMed

    Northoff, Georg

    2017-03-28

    Neuroimaging provided much insight into the neural activity of the brain and its alterations in psychiatric disorders. However, despite extensive research, the exact neuronal mechanisms leading to the various psychopathological symptoms remain unclear, yet. In addition to task-evoked activity during affective, cognitive, or other challenges, the brain's spontaneous or resting state activity has come increasingly into the focus. Basically all psychiatric disorders show abnormal resting state activity with the relation to psychopathological symptoms remaining unclear though. I here suggest to conceive the brain's spontaneous activity in spatiotemporal terms that is, by various mechanisms that are based on its spatial, i.e., functional connectivity, and temporal, i.e., fluctuations in different frequencies, features. I here point out two such spatiotemporal mechanisms, i.e., "spatiotemporal binding and integration". Alterations in the resting state's spatial and temporal features lead to abnormal "spatiotemporal binding and integration" which results in abnormal contents in cognition as in the various psychopathological symptoms. This, together with concrete empirical evidence, is demonstrated in depression and schizophrenia. I therefore conclude that we need to develop a spatiotemporal approach to psychopathology, "spatiotemporal psychopathology:" as I call it.

  11. Comparative Evaluation for Brain Structural Connectivity Approaches: Towards Integrative Neuroinformatics Tool for Epilepsy Clinical Research

    PubMed Central

    Yang, Sheng; Tatsuoka, Curtis; Ghosh, Kaushik; Lacuey-Lecumberri, Nuria; Lhatoo, Samden D.; Sahoo, Satya S.

    2016-01-01

    Recent advances in brain fiber tractography algorithms and diffusion Magnetic Resonance Imaging (MRI) data collection techniques are providing new approaches to study brain white matter connectivity, which play an important role in complex neurological disorders such as epilepsy. Epilepsy affects approximately 50 million persons worldwide and it is often described as a disorder of the cortical network organization. There is growing recognition of the need to better understand the role of brain structural networks in the onset and propagation of seizures in epilepsy using high resolution non-invasive imaging technologies. In this paper, we perform a comparative evaluation of two techniques to compute structural connectivity, namely probabilistic fiber tractography and statistics derived from fractional anisotropy (FA), using diffusion MRI data from a patient with rare case of medically intractable insular epilepsy. The results of our evaluation demonstrate that probabilistic fiber tractography provides a more accurate map of structural connectivity and may help address inherent complexities of neural fiber layout in the brain, such as fiber crossings. This work provides an initial result towards building an integrative informatics tool for neuroscience that can be used to accurately characterize the role of fiber tract connectivity in neurological disorders such as epilepsy. PMID:27570685

  12. Beta-trace Protein as a new non-invasive immunological Marker for Quinolinic Acid-induced impaired Blood-Brain Barrier Integrity

    PubMed Central

    Baranyi, Andreas; Amouzadeh-Ghadikolai, Omid; Lewinski, Dirk von; Breitenecker, Robert J.; Stojakovic, Tatjana; März, Winfried; Robier, Christoph; Rothenhäusler, Hans-Bernd; Mangge, Harald; Meinitzer, Andreas

    2017-01-01

    Quinolinic acid, a macrophage/microglia-derived excitotoxin fulfills a plethora of functions such as neurotoxin, gliotoxin, and proinflammatory mediator, and it alters the integrity and cohesion of the blood-brain barrier in several pathophysiological states. Beta-trace protein (BTP), a monomeric glycoprotein, is known to indicate cerebrospinal fluid leakage. Thus, the prior aim of this study was to investigate whether BTP might non-invasively indicate quinolinic acid-induced impaired blood-brain barrier integrity. The research hypotheses were tested in three subsamples with different states of immune activation (patients with HCV-infection and interferon-α, patients with major depression, and healthy controls). BTP has also been described as a sensitive marker in detecting impaired renal function. Thus, the renal function has been considered. Our study results revealed highest quinolinic acid and highest BTP- levels in the subsample of patients with HCV in comparison with the other subsamples with lower or no immune activation (quinolinic acid: F = 21.027, p < 0.001 [ANOVA]; BTP: F = 6.792, p < 0.01 [ANOVA]). In addition, a two-step hierarchical linear regression model showed that significant predictors of BTP levels are quinolinic acid, glomerular filtration rate and age. The neurotoxin quinolinic acid may impair blood-brain barrier integrity. BTP might be a new non-invasive biomarker to indicate quinolinic acid-induced impaired blood-brain barrier integrity. PMID:28276430

  13. The Virtual Brain: Modeling Biological Correlates of Recovery after Chronic Stroke

    PubMed Central

    Falcon, Maria Inez; Riley, Jeffrey D.; Jirsa, Viktor; McIntosh, Anthony R.; Shereen, Ahmed D.; Chen, E. Elinor; Solodkin, Ana

    2015-01-01

    There currently remains considerable variability in stroke survivor recovery. To address this, developing individualized treatment has become an important goal in stroke treatment. As a first step, it is necessary to determine brain dynamics associated with stroke and recovery. While recent methods have made strides in this direction, we still lack physiological biomarkers. The Virtual Brain (TVB) is a novel application for modeling brain dynamics that simulates an individual’s brain activity by integrating their own neuroimaging data with local biophysical models. Here, we give a detailed description of the TVB modeling process and explore model parameters associated with stroke. In order to establish a parallel between this new type of modeling and those currently in use, in this work we establish an association between a specific TVB parameter (long-range coupling) that increases after stroke with metrics derived from graph analysis. We used TVB to simulate the individual BOLD signals for 20 patients with stroke and 10 healthy controls. We performed graph analysis on their structural connectivity matrices calculating degree centrality, betweenness centrality, and global efficiency. Linear regression analysis demonstrated that long-range coupling is negatively correlated with global efficiency (P = 0.038), but is not correlated with degree centrality or betweenness centrality. Our results suggest that the larger influence of local dynamics seen through the long-range coupling parameter is closely associated with a decreased efficiency of the system. We thus propose that the increase in the long-range parameter in TVB (indicating a bias toward local over global dynamics) is deleterious because it reduces communication as suggested by the decrease in efficiency. The new model platform TVB hence provides a novel perspective to understanding biophysical parameters responsible for global brain dynamics after stroke, allowing the design of focused therapeutic

  14. The Virtual Brain: Modeling Biological Correlates of Recovery after Chronic Stroke.

    PubMed

    Falcon, Maria Inez; Riley, Jeffrey D; Jirsa, Viktor; McIntosh, Anthony R; Shereen, Ahmed D; Chen, E Elinor; Solodkin, Ana

    2015-01-01

    There currently remains considerable variability in stroke survivor recovery. To address this, developing individualized treatment has become an important goal in stroke treatment. As a first step, it is necessary to determine brain dynamics associated with stroke and recovery. While recent methods have made strides in this direction, we still lack physiological biomarkers. The Virtual Brain (TVB) is a novel application for modeling brain dynamics that simulates an individual's brain activity by integrating their own neuroimaging data with local biophysical models. Here, we give a detailed description of the TVB modeling process and explore model parameters associated with stroke. In order to establish a parallel between this new type of modeling and those currently in use, in this work we establish an association between a specific TVB parameter (long-range coupling) that increases after stroke with metrics derived from graph analysis. We used TVB to simulate the individual BOLD signals for 20 patients with stroke and 10 healthy controls. We performed graph analysis on their structural connectivity matrices calculating degree centrality, betweenness centrality, and global efficiency. Linear regression analysis demonstrated that long-range coupling is negatively correlated with global efficiency (P = 0.038), but is not correlated with degree centrality or betweenness centrality. Our results suggest that the larger influence of local dynamics seen through the long-range coupling parameter is closely associated with a decreased efficiency of the system. We thus propose that the increase in the long-range parameter in TVB (indicating a bias toward local over global dynamics) is deleterious because it reduces communication as suggested by the decrease in efficiency. The new model platform TVB hence provides a novel perspective to understanding biophysical parameters responsible for global brain dynamics after stroke, allowing the design of focused therapeutic

  15. An integrated data model for reservoir simulation

    SciTech Connect

    Aydelotte, S.R.

    1994-02-01

    This paper describes the capability of the Epicenter data model to manage reservoir-simulation information, including the spatial model used to describe the properties of the earth and the product-flow network mode used to describe production performance. In addition to data values, the data model describes data creation and quality and provides a reliable means of understanding the source. To use the data model, reservoir-simulation applications need to be rewritten to conform to the data-model nomenclature and conventions. While this is a significant task, the benefit to reservoir simulation practitioners and vendors includes integration of technical applications (such as mapping, well logging, and geophysical interpretation systems), data portability (allowing Vendor A's simulator to use data prepared by Vendor B's preprocessor), and interpretability such as using a third-party optimization package to conduct a series of simulations.

  16. Blast and the Consequences on Traumatic Brain Injury-Multiscale Mechanical Modeling of Brain

    DTIC Science & Technology

    2011-02-17

    exposed to the Nahum head test scenarios. 4. Simulations under Blast Shock Waves Publication #s: [9], [10], [11], [41], [43] At many blast...the head model for three explosive scenarios[43]. Figure 8. Relative displacement-time histories for two clusters of a particular test with...Blasts, Brain Injury Professional, 2007;4(1), 10-15. [2] Naik , N. Abolfathi, G. Karami and M. Ziejewski, Micromechanical Viscoelastic

  17. Through the Immune Looking Glass: A Model for Brain Memory Strategies

    PubMed Central

    Sánchez-Ramón, Silvia; Faure, Florence

    2016-01-01

    The immune system (IS) and the central nervous system (CNS) are complex cognitive networks involved in defining the identity (self) of the individual through recognition and memory processes that enable one to anticipate responses to stimuli. Brain memory has traditionally been classified as either implicit or explicit on psychological and anatomical grounds, with reminiscences of the evolutionarily-based innate-adaptive IS responses. Beyond the multineuronal networks of the CNS, we propose a theoretical model of brain memory integrating the CNS as a whole. This is achieved by analogical reasoning between the operational rules of recognition and memory processes in both systems, coupled to an evolutionary analysis. In this new model, the hippocampus is no longer specifically ascribed to explicit memory but rather it both becomes part of the innate (implicit) memory system and tightly controls the explicit memory system. Alike the antigen presenting cells for the IS, the hippocampus would integrate transient and pseudo-specific (i.e., danger-fear) memories and would drive the formation of long-term and highly specific or explicit memories (i.e., the taste of the Proust’s madeleine cake) by the more complex and recent, evolutionarily speaking, neocortex. Experimental and clinical evidence is provided to support the model. We believe that the singularity of this model’s approximation could help to gain a better understanding of the mechanisms operating in brain memory strategies from a large-scale network perspective. PMID:26869886

  18. Plant design: Integrating Plant and Equipment Models

    SciTech Connect

    Sloan, David; Fiveland, Woody; Zitney, S.E.; Osawe, Maxwell

    2007-08-01

    Like power plant engineers, process plant engineers must design generating units to operate efficiently, cleanly, and profitably despite fluctuating costs for raw materials and fuels. To do so, they increasingly create virtual plants to enable evaluation of design concepts without the expense of building pilot-scale or demonstration facilities. Existing computational models describe an entire plant either as a network of simplified equipment models or as a single, very detailed equipment model. The Advanced Process Engineering Co-Simulator (APECS) project (Figure 5) sponsored by the U.S. Department of Energy's National Energy Technology Laboratory (NETL) seeks to bridge the gap between models by integrating plant modeling and equipment modeling software. The goal of the effort is to provide greater insight into the performance of proposed plant designs. The software integration was done using the process-industry standard CAPE-OPEN (Computer Aided Process Engineering–Open), or CO interface. Several demonstration cases based on operating power plants confirm the viability of this co-simulation approach.

  19. The Integrated Airport Competition Model, 1998

    NASA Technical Reports Server (NTRS)

    Veldhuis, J.; Essers, I.; Bakker, D.; Cohn, N.; Kroes, E.

    1999-01-01

    This paper addresses recent model development by the Directorate General of Civil Aviation (DGCA) and Hague Consulting Group (HCG) concerning long-distance travel, Long-distance travel demand is growing very quickly and raising a great deal of economic and policy issues. There is increasing competition among the main Western European airports, and smaller, regional airports are fighting for market share. New modes of transport, such as high speed rail, arc also coming into the picture and affect the mode split for medium distance transport within Europe. Developments such as these are demanding the attention of policy makers and a tool is required for their analysis. For DGCA, Hague Consulting Group has developed a model system to provide answers to the policy questions posed by these expected trends, and to identify areas where policy makers can influence the traveller choices. The development of this model system, the Integrated Airport Competition Model/Integral Luchthaven Competitive Model (ILCM), began in 1992. Since that time the sub-models, input data and user interface have been expanded, updated and improved. HCG and DGCA have transformed the ILCM from a prototype into an operational forecasting tool.

  20. Modelling Brain Temperature and Perfusion for Cerebral Cooling

    NASA Astrophysics Data System (ADS)

    Blowers, Stephen; Valluri, Prashant; Marshall, Ian; Andrews, Peter; Harris, Bridget; Thrippleton, Michael

    2015-11-01

    Brain temperature relies heavily on two aspects: i) blood perfusion and porous heat transport through tissue and ii) blood flow and heat transfer through embedded arterial and venous vasculature. Moreover brain temperature cannot be measured directly unless highly invasive surgical procedures are used. A 3D two-phase fluid-porous model for mapping flow and temperature in brain is presented with arterial and venous vessels extracted from MRI scans. Heat generation through metabolism is also included. The model is robust and reveals flow and temperature maps in unprecedented 3D detail. However, the Karmen-Kozeny parameters of the porous (tissue) phase need to be optimised for expected perfusion profiles. In order to optimise the K-K parameters a reduced order two-phase model is developed where 1D vessels are created with a tree generation algorithm embedded inside a 3D porous domain. Results reveal that blood perfusion is a strong function of the porosity distribution in the tissue. We present a qualitative comparison between the simulated perfusion maps and those obtained clinically. We also present results studying the effect of scalp cooling on core brain temperature and preliminary results agree with those observed clinically.

  1. Models to Tailor Brain Stimulation Therapies in Stroke.

    PubMed

    Plow, E B; Sankarasubramanian, V; Cunningham, D A; Potter-Baker, K; Varnerin, N; Cohen, L G; Sterr, A; Conforto, A B; Machado, A G

    2016-01-01

    A great challenge facing stroke rehabilitation is the lack of information on how to derive targeted therapies. As such, techniques once considered promising, such as brain stimulation, have demonstrated mixed efficacy across heterogeneous samples in clinical studies. Here, we explain reasons, citing its one-type-suits-all approach as the primary cause of variable efficacy. We present evidence supporting the role of alternate substrates, which can be targeted instead in patients with greater damage and deficit. Building on this groundwork, this review will also discuss different frameworks on how to tailor brain stimulation therapies. To the best of our knowledge, our report is the first instance that enumerates and compares across theoretical models from upper limb recovery and conditions like aphasia and depression. Here, we explain how different models capture heterogeneity across patients and how they can be used to predict which patients would best respond to what treatments to develop targeted, individualized brain stimulation therapies. Our intent is to weigh pros and cons of testing each type of model so brain stimulation is successfully tailored to maximize upper limb recovery in stroke.

  2. Silencing microRNA-143 protects the integrity of the blood-brain barrier: implications for methamphetamine abuse

    PubMed Central

    Bai, Ying; Zhang, Yuan; Hua, Jun; Yang, Xiangyu; Zhang, Xiaotian; Duan, Ming; Zhu, Xinjian; Huang, Wenhui; Chao, Jie; Zhou, Rongbin; Hu, Gang; Yao, Honghong

    2016-01-01

    MicroRNA-143 (miR-143) plays a critical role in various cellular processes; however, the role of miR-143 in the maintenance of blood-brain barrier (BBB) integrity remains poorly defined. Silencing miR-143 in a genetic animal model or via an anti-miR-143 lentivirus prevented the BBB damage induced by methamphetamine. miR-143, which targets p53 unregulated modulator of apoptosis (PUMA), increased the permeability of human brain endothelial cells and concomitantly decreased the expression of tight junction proteins (TJPs). Silencing miR-143 increased the expression of TJPs and protected the BBB integrity against the effects of methamphetamine treatment. PUMA overexpression increased the TJP expression through a mechanism that involved the NF-κB and p53 transcription factor pathways. Mechanistically, methamphetamine mediated up-regulation of miR-143 via sigma-1 receptor with sequential activation of the mitogen-activated protein kinase (MAPK) and phosphatidylinositol-3′ kinase (PI3K)/Akt and STAT3 pathways. These results indicated that silencing miR-143 could provide a novel therapeutic strategy for BBB damage-related vascular dysfunction. PMID:27767041

  3. Treatment of penetrating brain injury in a rat model using collagen scaffolds incorporating soluble Nogo receptor.

    PubMed

    Elias, Paul Z; Spector, Myron

    2015-02-01

    Injuries and diseases of the central nervous system (CNS) have the potential to cause permanent loss of brain parenchyma, with severe neurological consequences. Cavitary defects in the brain may afford the possibility of treatment with biomaterials that fill the lesion site while delivering therapeutic agents. This study examined the treatment of penetrating brain injury (PBI) in a rat model with collagen biomaterials and a soluble Nogo receptor (sNgR) molecule. sNgR was aimed at neutralizing myelin proteins that hinder axon regeneration by inducing growth cone collapse. Scaffolds containing sNgR were implanted in the brains of adult rats 1 week after injury and analysed 4 weeks or 8 weeks later. Histological analysis revealed that the scaffolds filled the lesion sites, remained intact with open pores and were infiltrated with cells and extracellular matrix. Immunohistochemical staining demonstrated the composition of the cellular infiltrate to include macrophages, astrocytes and vascular endothelial cells. Isolated regions of the scaffold borders showed integration with surrounding viable brain tissue that included neurons and oligodendrocytes. While axon regeneration was not detected in the scaffolds, the cellular infiltration and vascularization of the lesion site demonstrated a modification of the injury environment with implications for regenerative strategies.

  4. Integrated modeling of advanced optical systems

    NASA Technical Reports Server (NTRS)

    Briggs, Hugh C.; Needels, Laura; Levine, B. Martin

    1993-01-01

    This poster session paper describes an integrated modeling and analysis capability being developed at JPL under funding provided by the JPL Director's Discretionary Fund and the JPL Control/Structure Interaction Program (CSI). The posters briefly summarize the program capabilities and illustrate them with an example problem. The computer programs developed under this effort will provide an unprecedented capability for integrated modeling and design of high performance optical spacecraft. The engineering disciplines supported include structural dynamics, controls, optics and thermodynamics. Such tools are needed in order to evaluate the end-to-end system performance of spacecraft such as OSI, POINTS, and SMMM. This paper illustrates the proof-of-concept tools that have been developed to establish the technology requirements and demonstrate the new features of integrated modeling and design. The current program also includes implementation of a prototype tool based upon the CAESY environment being developed under the NASA Guidance and Control Research and Technology Computational Controls Program. This prototype will be available late in FY-92. The development plan proposes a major software production effort to fabricate, deliver, support and maintain a national-class tool from FY-93 through FY-95.

  5. Approximated integrability of the Dicke model

    NASA Astrophysics Data System (ADS)

    Relaño, A.; Bastarrachea-Magnani, M. A.; Lerma-Hernández, S.

    2016-12-01

    A very approximate second integral of motion of the Dicke model is identified within a broad energy region above the ground state, and for a wide range of values of the external parameters. This second integral, obtained from a Born-Oppenheimer approximation, classifies the whole regular part of the spectrum in bands, coming from different semi-classical energy surfaces, and labelled by its corresponding eigenvalues. Results obtained from this approximation are compared with exact numerical diagonalization for finite systems in the superradiant phase, obtaining a remarkable accord. The region of validity of our approach in the parameter space, which includes the resonant case, is unveiled. The energy range of validity goes from the ground state up to a certain upper energy where chaos sets in, and extends far beyond the range of applicability of a simple harmonic approximation around the minimal energy configuration. The upper energy validity limit increases for larger values of the coupling constant and the ratio between the level splitting and the frequency of the field. These results show that the Dicke model behaves like a two-degree-of-freedom integrable model for a wide range of energies and values of the external parameters.

  6. Fuzzy local Gaussian mixture model for brain MR image segmentation.

    PubMed

    Ji, Zexuan; Xia, Yong; Sun, Quansen; Chen, Qiang; Xia, Deshen; Feng, David Dagan

    2012-05-01

    Accurate brain tissue segmentation from magnetic resonance (MR) images is an essential step in quantitative brain image analysis. However, due to the existence of noise and intensity inhomogeneity in brain MR images, many segmentation algorithms suffer from limited accuracy. In this paper, we assume that the local image data within each voxel's neighborhood satisfy the Gaussian mixture model (GMM), and thus propose the fuzzy local GMM (FLGMM) algorithm for automated brain MR image segmentation. This algorithm estimates the segmentation result that maximizes the posterior probability by minimizing an objective energy function, in which a truncated Gaussian kernel function is used to impose the spatial constraint and fuzzy memberships are employed to balance the contribution of each GMM. We compared our algorithm to state-of-the-art segmentation approaches in both synthetic and clinical data. Our results show that the proposed algorithm can largely overcome the difficulties raised by noise, low contrast, and bias field, and substantially improve the accuracy of brain MR image segmentation.

  7. Animal models of traumatic brain injury: is there an optimal model to reproduce human brain injury in the laboratory?

    PubMed

    Morganti-Kossmann, M C; Yan, E; Bye, N

    2010-07-01

    Compared to other neurological diseases, the research surrounding traumatic brain injury (TBI) has a more recent history. The establishment and use of animal models of TBI remains vital to understand the pathophysiology of this highly complex disease. Such models share the ultimate goals of reproducing patterns of tissue damage observed in humans (thus rendering them clinically relevant), reproducible and highly standardised to allow for the manipulation of individual variables, and to finally explore novel therapeutics for clinical translation. There is no doubt that the similarity of cellular and molecular events observed in human and rodent TBI has reinforced the use of small animals for research. When confronted with the choice of the experimental model it becomes clear that the ideal animal model does not exist. This limitation derives from the fact that most models mimic either focal or diffuse brain injury, whereas the clinical reality suggests that each patient has an individual form of TBI characterised by various combinations of focal and diffuse patterns of tissue damage. This is additionally complicated by the occurrence of secondary insults such as hypotension, hypoxia, ischaemia, extracranial injuries, modalities of traumatic events, age, gender and heterogeneity of medical treatments and pre-existing conditions. This brief review will describe the variety of TBI models available for laboratory research beginning from the most widely used rodent models of focal brain trauma, to complex large species such as the pig. In addition, the models mimicking diffuse brain damage will be discussed in relation to the early primate studies until the use of most common rodent models to elucidate the intriguing and less understood pathology of axonal dysfunction. The most recent establishment of in vitro paradigms has complemented the in vivo modelling studies offering a further cellular and molecular insight of this pathology.

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

    PubMed Central

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

    2015-01-01

    Based on the Huttenlocher lecture, this article describes the need for a more integrative scientific paradigm for addressing important questions raised by key observations made over 2 decades ago. Among these are the early descriptions by Huttenlocher of variability in synaptic density in cortex of postmortem brains of children of different ages and the almost simultaneous reports of cortical volume reductions on MR imaging in children and adolescents. In spite of much progress in developmental neurobiology, developmental cognitive neuroscience, and behavioral and imaging genetics, we still do not know how these early observations relate to each other. It is argued that large scale, collaborative research programs are needed to establish the associations between behavioral differences among children and imaging biomarkers, and to link the latter to cellular changes in the developing brain. Examples of progress and challenges remaining are illustrated with data from the Pediatric Imaging, Neurocognition, and Genetics Project (PING). PMID:26347228

  9. Interleukin-34 restores blood-brain barrier integrity by upregulating tight junction proteins in endothelial cells.

    PubMed

    Jin, Shijie; Sonobe, Yoshifumi; Kawanokuchi, Jun; Horiuchi, Hiroshi; Cheng, Yi; Wang, Yue; Mizuno, Tetsuya; Takeuchi, Hideyuki; Suzumura, Akio

    2014-01-01

    Interleukin-34 (IL-34) is a newly discovered cytokine as an additional ligand for colony stimulating factor-1 receptor (CSF1R), and its functions are expected to overlap with colony stimulating factor-1/macrophage-colony stimulating factor. We have previously shown that the IL-34 is primarily produced by neurons in the central nervous system (CNS) and induces proliferation and neuroprotective properties of microglia which express CSF1R. However, the functions of IL-34 in the CNS are still elucidative. Here we show that CNS capillary endothelial cells also express CSF1R. IL-34 protected blood-brain barrier integrity by restored expression levels of tight junction proteins, which were downregulated by pro-inflammatory cytokines. The novel function of IL-34 on the blood-brain barrier may give us a clue for new therapeutic strategies in neuroinflammatory and neurodegenerative diseases such as multiple sclerosis and Alzheimer's disease.

  10. Interleukin-34 Restores Blood–Brain Barrier Integrity by Upregulating Tight Junction Proteins in Endothelial Cells

    PubMed Central

    Jin, Shijie; Sonobe, Yoshifumi; Kawanokuchi, Jun; Horiuchi, Hiroshi; Cheng, Yi; Wang, Yue; Mizuno, Tetsuya; Takeuchi, Hideyuki; Suzumura, Akio

    2014-01-01

    Interleukin-34 (IL-34) is a newly discovered cytokine as an additional ligand for colony stimulating factor-1 receptor (CSF1R), and its functions are expected to overlap with colony stimulating factor-1/macrophage-colony stimulating factor. We have previously shown that the IL-34 is primarily produced by neurons in the central nervous system (CNS) and induces proliferation and neuroprotective properties of microglia which express CSF1R. However, the functions of IL-34 in the CNS are still elucidative. Here we show that CNS capillary endothelial cells also express CSF1R. IL-34 protected blood–brain barrier integrity by restored expression levels of tight junction proteins, which were downregulated by pro-inflammatory cytokines. The novel function of IL-34 on the blood–brain barrier may give us a clue for new therapeutic strategies in neuroinflammatory and neurodegenerative diseases such as multiple sclerosis and Alzheimer's disease. PMID:25535736

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

    PubMed

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

    2016-04-01

    Based on the Huttenlocher lecture, this article describes the need for a more integrative scientific paradigm for addressing important questions raised by key observations made over 2 decades ago. Among these are the early descriptions by Huttenlocher of variability in synaptic density in cortex of postmortem brains of children of different ages and the almost simultaneous reports of cortical volume reductions on MR imaging in children and adolescents. In spite of much progress in developmental neurobiology, developmental cognitive neuroscience, and behavioral and imaging genetics, we still do not know how these early observations relate to each other. It is argued that large scale, collaborative research programs are needed to establish the associations between behavioral differences among children and imaging biomarkers, and to link the latter to cellular changes in the developing brain. Examples of progress and challenges remaining are illustrated with data from the Pediatric Imaging, Neurocognition, and Genetics Project (PING).

  12. Collision detection as a model for sensory-motor integration.

    PubMed

    Fotowat, Haleh; Gabbiani, Fabrizio

    2011-01-01

    Visually guided collision avoidance is critical for the survival of many animals. The execution of successful collision-avoidance behaviors requires accurate processing of approaching threats by the visual system and signaling of threat characteristics to motor circuits to execute appropriate motor programs in a timely manner. Consequently, visually guided collision avoidance offers an excellent model with which to study the neural mechanisms of sensory-motor integration in the context of a natural behavior. Neurons that selectively respond to approaching threats and brain areas processing them have been characterized across many species. In locusts in particular, the underlying sensory and motor processes have been analyzed in great detail: These animals possess an identified neuron, called the LGMD, that responds selectively to approaching threats and conveys that information through a second identified neuron, the DCMD, to motor centers, generating escape jumps. A combination of behavioral and in vivo electrophysiological experiments has unraveled many of the cellular and network mechanisms underlying this behavior.

  13. Dosha brain-types: A neural model of individual differences

    PubMed Central

    Travis, Frederick T.; Wallace, Robert Keith

    2015-01-01

    This paper explores brain patterns associated with the three categories of regulatory principles of the body, mind, and behavior in Ayurveda, called Vata, Pitta, and Kapha dosha. A growing body of research has reported patterns of blood chemistry, genetic expression, physiological states, and chronic diseases associated with each dosha type. Since metabolic and growth factors are controlled by the nervous system, each dosha type should be associated with patterns of functioning of six major areas of the nervous system: The prefrontal cortex, the reticular activating system, the autonomic nervous system, the enteric nervous system, the limbic system, and the hypothalamus. For instance, the prefrontal cortex, which includes the anterior cingulate, ventral medial, and the dorsal lateral cortices, would exhibit a high range of functioning in the Vata brain-type leading to the possibility of being easily overstimulated. The Vata brain-type performs activity quickly. Learns quickly and forgets quickly. Their fast mind gives them an edge in creative problem solving. The Pitta brain-type reacts strongly to all challenges leading to purposeful and resolute actions. They never give up and are very dynamic and goal oriented. The Kapha brain-type is slow and steady leading to methodical thinking and action. They prefer routine and needs stimulation to get going. A model of dosha brain-types could provide a physiological foundation to understand individual differences. This model could help individualize treatment modalities to address different mental and physical dysfunctions. It also could explain differences in behavior seen in clinical as well as in normal populations. PMID:26834428

  14. An integrated neuromechanical model of insect locomotion

    NASA Astrophysics Data System (ADS)

    Kukillaya, Raghavendra

    We develop a biologically-plausible feedforward neuromechanical model for running insects that includes a simplified hexapedal leg geometry with agonist-antagonist muscle pairs actuating each leg joint. It is driven by a neural network modeling the central pattern generator (CPG) and the motoneurons which activate the muscles. This final goal is achieved in three stages. First, a relatively simple mechanical hexapedal model is constructed in which the joint torques are produced via actuated linear torsional springs with constant stiffness. In the second stage, this system is upgraded to a muscle-actuated hexapedal model in which each joint is actuated by a pair of agonist-antagonist Hill-type muscles. Muscles are driven by stylized action potentials that are characteristic of fast motoneurons, and modeled using an activation function and nonlinear length and shortening velocity dependence. In the final stage, the full neuromechanical model is obtained by integrating the above muscle-actuated hexapedal model with a CPG-motoneuron complex, feedforward input to the muscles now being supplied by action potentials from motoneurons. Restricting to dynamics in the horizontal plane and neglecting leg masses, we reduce the model (at each stage) to three degrees of freedom describing translational and yawing motions of the body. Collectively for all the models, parameter values are based on measurements from depressor motoneurons and muscles, and observations of kinematics and dynamics of the cockroach Blaberus discoidalis. Specifically, actuation inputs for the mechanical and muscle-actuated models are chosen to approximately achieve joint torques that are consistent with measured ground reaction forces. This is done by optimizing the time-dependent torque-free joint angles in the first model, and by optimizing motoneuronal outputs and muscle force levels in the second and third models. We show that the model (at each stage) has stable double-tripod gaits over the animal

  15. Dimethyl fumarate attenuates cerebral edema formation by protecting the blood-brain barrier integrity.

    PubMed

    Kunze, Reiner; Urrutia, Andrés; Hoffmann, Angelika; Liu, Hui; Helluy, Xavier; Pham, Mirko; Reischl, Stefan; Korff, Thomas; Marti, Hugo H

    2015-04-01

    Brain edema is a hallmark of various neuropathologies, but the underlying mechanisms are poorly understood. We aim to characterize how tissue hypoxia, together with oxidative stress and inflammation, leads to capillary dysfunction and breakdown of the blood-brain barrier (BBB). In a mouse stroke model we show that systemic treatment with dimethyl fumarate (DMF), an antioxidant drug clinically used for psoriasis and multiple sclerosis, significantly prevented edema formation in vivo. Indeed, DMF stabilized the BBB by preventing disruption of interendothelial tight junctions and gap formation, and decreased matrix metalloproteinase activity in brain tissue. In vitro, DMF directly sustained endothelial tight junctions, inhibited inflammatory cytokine expression, and attenuated leukocyte transmigration. We also demonstrate that these effects are mediated via activation of the redox sensitive transcription factor NF-E2 related factor 2 (Nrf2). DMF activated the Nrf2 pathway as shown by up-regulation of several Nrf2 target genes in the brain in vivo, as well as in cerebral endothelial cells and astrocytes in vitro, where DMF also increased protein abundance of nuclear Nrf2. Finally, Nrf2 knockdown in endothelial cells aggravated subcellular delocalization of tight junction proteins during ischemic conditions, and attenuated the protective effect exerted by DMF. Overall, our data suggest that DMF protects from cerebral edema formation during ischemic stroke by targeting interendothelial junctions in an Nrf2-dependent manner, and provide the basis for a completely new approach to treat brain edema.

  16. Integrated Model for E-Learning Acceptance

    NASA Astrophysics Data System (ADS)

    Ramadiani; Rodziah, A.; Hasan, S. M.; Rusli, A.; Noraini, C.

    2016-01-01

    E-learning is not going to work if the system is not used in accordance with user needs. User Interface is very important to encourage using the application. Many theories had discuss about user interface usability evaluation and technology acceptance separately, actually why we do not make it correlation between interface usability evaluation and user acceptance to enhance e-learning process. Therefore, the evaluation model for e-learning interface acceptance is considered important to investigate. The aim of this study is to propose the integrated e-learning user interface acceptance evaluation model. This model was combined some theories of e-learning interface measurement such as, user learning style, usability evaluation, and the user benefit. We formulated in constructive questionnaires which were shared at 125 English Language School (ELS) students. This research statistics used Structural Equation Model using LISREL v8.80 and MANOVA analysis.

  17. Multiscale modeling for image analysis of brain tumor studies.

    PubMed

    Bauer, Stefan; May, Christian; Dionysiou, Dimitra; Stamatakos, Georgios; Büchler, Philippe; Reyes, Mauricio

    2012-01-01

    Image-based modeling of tumor growth combines methods from cancer simulation and medical imaging. In this context, we present a novel approach to adapt a healthy brain atlas to MR images of tumor patients. In order to establish correspondence between a healthy atlas and a pathologic patient image, tumor growth modeling in combination with registration algorithms is employed. In a first step, the tumor is grown in the atlas based on a new multiscale, multiphysics model including growth simulation from the cellular level up to the biomechanical level, accounting for cell proliferation and tissue deformations. Large-scale deformations are handled with an Eulerian approach for finite element computations, which can operate directly on the image voxel mesh. Subsequently, dense correspondence between the modified atlas and patient image is established using nonrigid registration. The method offers opportunities in atlas-based segmentation of tumor-bearing brain images as well as for improved patient-specific simulation and prognosis of tumor progression.

  18. Self-organized criticality model for brain plasticity.

    PubMed

    de Arcangelis, Lucilla; Perrone-Capano, Carla; Herrmann, Hans J

    2006-01-20

    Networks of living neurons exhibit an avalanche mode of activity, experimentally found in organotypic cultures. Here we present a model that is based on self-organized criticality and takes into account brain plasticity, which is able to reproduce the spectrum of electroencephalograms (EEG). The model consists of an electrical network with threshold firing and activity-dependent synapse strengths. The system exhibits an avalanche activity in a power-law distribution. The analysis of the power spectra of the electrical signal reproduces very robustly the power-law behavior with the exponent 0.8, experimentally measured in EEG spectra. The same value of the exponent is found on small-world lattices and for leaky neurons, indicating that universality holds for a wide class of brain models.

  19. Neuroinflammation in animal models of traumatic brain injury

    PubMed Central

    Chiu, Chong-Chi; Liao, Yi-En; Yang, Ling-Yu; Wang, Jing-Ya; Tweedie, David; Karnati, Hanuma K.; Greig, Nigel H.; Wang, Jia-Yi

    2016-01-01

    Traumatic brain injury (TBI) is a leading cause of mortality and morbidity worldwide. Neuroinflammation is prominent in the short and long-term consequences of neuronal injuries that occur after TBI. Neuroinflammation involves the activation of glia, including microglia and astrocytes, to release inflammatory mediators within the brain, and the subsequent recruitment of peripheral immune cells. Various animal models of TBI have been developed that have proved valuable to elucidate the pathophysiology of the disorder and to assess the safety and efficacy of novel therapies prior to clinical trials. These models provide an excellent platform to delineate key injury mechanisms that associate with types of injury (concussion, contusion, and penetration injuries) that occur clinically for the investigation of mild, moderate, and severe forms of TBI. Additionally, TBI modeling in genetically engineered mice, in particular, has aided the identification of key molecules and pathways for putative injury mechanisms, as targets for development of novel therapies for human TBI. This Review details the evidence showing that neuroinflammation, characterized by the activation of microglia and astrocytes and elevated production of inflammatory mediators, is a critical process occurring in various TBI animal models, provides a broad overview of commonly used animal models of TBI, and overviews representative techniques to quantify markers of the brain inflammatory process. A better understanding of neuroinflammation could open therapeutic avenues for abrogation of secondary cell death and behavioral symptoms that may mediate the progression of TBI. PMID:27382003

  20. MR Vascular Fingerprinting in Stroke and Brain Tumors Models

    NASA Astrophysics Data System (ADS)

    Lemasson, B.; Pannetier, N.; Coquery, N.; Boisserand, Ligia S. B.; Collomb, Nora; Schuff, N.; Moseley, M.; Zaharchuk, G.; Barbier, E. L.; Christen, T.

    2016-11-01

    In this study, we evaluated an MRI fingerprinting approach (MRvF) designed to provide high-resolution parametric maps of the microvascular architecture (i.e., blood volume fraction, vessel diameter) and function (blood oxygenation) simultaneously. The method was tested in rats (n = 115), divided in 3 models: brain tumors (9 L, C6, F98), permanent stroke, and a control group of healthy animals. We showed that fingerprinting can robustly distinguish between healthy and pathological brain tissues with different behaviors in tumor and stroke models. In particular, fingerprinting revealed that C6 and F98 glioma models have similar signatures while 9 L present a distinct evolution. We also showed that it is possible to improve the results of MRvF and obtain supplemental information by changing the numerical representation of the vascular network. Finally, good agreement was found between MRvF and conventional MR approaches in healthy tissues and in the C6, F98, and permanent stroke models. For the 9 L glioma model, fingerprinting showed blood oxygenation measurements that contradict results obtained with a quantitative BOLD approach. In conclusion, MR vascular fingerprinting seems to be an efficient technique to study microvascular properties in vivo. Multiple technical improvements are feasible and might improve diagnosis and management of brain diseases.

  1. MR Vascular Fingerprinting in Stroke and Brain Tumors Models

    PubMed Central

    Lemasson, B.; Pannetier, N.; Coquery, N.; Boisserand, Ligia S. B.; Collomb, Nora; Schuff, N.; Moseley, M.; Zaharchuk, G.; Barbier, E. L.; Christen, T.

    2016-01-01

    In this study, we evaluated an MRI fingerprinting approach (MRvF) designed to provide high-resolution parametric maps of the microvascular architecture (i.e., blood volume fraction, vessel diameter) and function (blood oxygenation) simultaneously. The method was tested in rats (n = 115), divided in 3 models: brain tumors (9 L, C6, F98), permanent stroke, and a control group of healthy animals. We showed that fingerprinting can robustly distinguish between healthy and pathological brain tissues with different behaviors in tumor and stroke models. In particular, fingerprinting revealed that C6 and F98 glioma models have similar signatures while 9 L present a distinct evolution. We also showed that it is possible to improve the results of MRvF and obtain supplemental information by changing the numerical representation of the vascular network. Finally, good agreement was found between MRvF and conventional MR approaches in healthy tissues and in the C6, F98, and permanent stroke models. For the 9 L glioma model, fingerprinting showed blood oxygenation measurements that contradict results obtained with a quantitative BOLD approach. In conclusion, MR vascular fingerprinting seems to be an efficient technique to study microvascular properties in vivo. Multiple technical improvements are feasible and might improve diagnosis and management of brain diseases. PMID:27883015

  2. MR Vascular Fingerprinting in Stroke and Brain Tumors Models.

    PubMed

    Lemasson, B; Pannetier, N; Coquery, N; Boisserand, Ligia S B; Collomb, Nora; Schuff, N; Moseley, M; Zaharchuk, G; Barbier, E L; Christen, T

    2016-11-24

    In this study, we evaluated an MRI fingerprinting approach (MRvF) designed to provide high-resolution parametric maps of the microvascular architecture (i.e., blood volume fraction, vessel diameter) and function (blood oxygenation) simultaneously. The method was tested in rats (n = 115), divided in 3 models: brain tumors (9 L, C6, F98), permanent stroke, and a control group of healthy animals. We showed that fingerprinting can robustly distinguish between healthy and pathological brain tissues with different behaviors in tumor and stroke models. In particular, fingerprinting revealed that C6 and F98 glioma models have similar signatures while 9 L present a distinct evolution. We also showed that it is possible to improve the results of MRvF and obtain supplemental information by changing the numerical representation of the vascular network. Finally, good agreement was found between MRvF and conventional MR approaches in healthy tissues and in the C6, F98, and permanent stroke models. For the 9 L glioma model, fingerprinting showed blood oxygenation measurements that contradict results obtained with a quantitative BOLD approach. In conclusion, MR vascular fingerprinting seems to be an efficient technique to study microvascular properties in vivo. Multiple technical improvements are feasible and might improve diagnosis and management of brain diseases.

  3. Breaking symmetry: the zebrafish as a model for understanding left-right asymmetry in the developing brain.

    PubMed

    Roussigne, Myriam; Blader, Patrick; Wilson, Stephen W

    2012-03-01

    How does left-right asymmetry develop in the brain and how does the resultant asymmetric circuitry impact on brain function and lateralized behaviors? By enabling scientists to address these questions at the levels of genes, neurons, circuitry and behavior,the zebrafish model system provides a route to resolve the complexity of brain lateralization. In this review, we present the progress made towards characterizing the nature of the gene networks and the sequence of morphogenetic events involved in the asymmetric development of zebrafish epithalamus. In an attempt to integrate the recent extensive knowledge into a working model and to identify the future challenges,we discuss how insights gained at a cellular/developmental level can be linked to the data obtained at a molecular/genetic level. Finally, we present some evolutionary thoughts and discuss how significant discoveries made in zebrafish should provide entry points to better understand the evolutionary origins of brain lateralization.

  4. Omics analysis of mouse brain models of human diseases.

    PubMed

    Paban, Véronique; Loriod, Béatrice; Villard, Claude; Buee, Luc; Blum, David; Pietropaolo, Susanna; Cho, Yoon H; Gory-Faure, Sylvie; Mansour, Elodie; Gharbi, Ali; Alescio-Lautier, Béatrice

    2017-02-05

    The identification of common gene/protein profiles related to brain alterations, if they exist, may indicate the convergence of the pathogenic mechanisms driving brain disorders. Six genetically engineered mouse lines modelling neurodegenerative diseases and neuropsychiatric disorders were considered. Omics approaches, including transcriptomic and proteomic methods, were used. The gene/protein lists were used for inter-disease comparisons and further functional and network investigations. When the inter-disease comparison was performed using the gene symbol identifiers, the number of genes/proteins involved in multiple diseases decreased rapidly. Thus, no genes/proteins were shared by all 6 mouse models. Only one gene/protein (Gfap) was shared among 4 disorders, providing strong evidence that a common molecular signature does not exist among brain diseases. The inter-disease comparison of functional processes showed the involvement of a few major biological processes indicating that brain diseases of diverse aetiologies might utilize common biological pathways in the nervous system, without necessarily involving similar molecules.

  5. Visualization tools: Models, representations and knowledge integration

    NASA Astrophysics Data System (ADS)

    Foley, Brian John

    Learning science requires students to make inferences and draw conclusions about concepts that are abstract, invisible or otherwise difficult to imagine. Scientific visualization is one way to make science and scientific thinking more visible to students. This dissertation investigates how visualization can be utilized for science education by studying how students integrate information from visualizations into their thinking. For this study, I developed a series of computer visualizations depicting thermodynamic phenomena. Thermodynamics is a topic that is both fundamental for several branches of science and difficult for many students to master (Linn & Songer, 1991). The design of the visualizations was learner centered. Pilot studies suggested that a dot-density representation of temperature would present a visual analogy of temperature as a measure of heat energy density. Energy density is a powerful model that can help students explain everyday heating and cooling phenomena. Dot-density computer visualizations were introduced into a public middle school science class studying thermodynamics (N = 178). Half of the students used the visualizations, while the other half served as a control. Interviews, classwork and tests were collected from the students in order to determine how the visualizations affected students' learning. Although there were not significant differences in the posttests for the groups, the classwork during the semester showed that the visualizations did affect how students envisioned heat and temperature. Students could often apply the energy density model in their reasoning during visualization activities, but when the visualizations were unavailable, many students applied less useful models. The interviews illustrated several difficulties that students had in learning from the visualizations. Some students interpreted the visualizations to support their existing conceptions of heat. Other students needed to have a visualization present to

  6. Lateral Fluid Percussion: Model of Traumatic Brain Injury in Mice

    PubMed Central

    Alder, Janet; Fujioka, Wendy; Lifshitz, Jonathan; Crockett, David P.; Thakker-Varia, Smita

    2011-01-01

    Traumatic brain injury (TBI) research has attained renewed momentum due to the increasing awareness of head injuries, which result in morbidity and mortality. Based on the nature of primary injury following TBI, complex and heterogeneous secondary consequences result, which are followed by regenerative processes 1,2. Primary injury can be induced by a direct contusion to the brain from skull fracture or from shearing and stretching of tissue causing displacement of brain due to movement 3,4. The resulting hematomas and lacerations cause a vascular response 3,5, and the morphological and functional damage of the white matter leads to diffuse axonal injury 6-8. Additional secondary changes commonly seen in the brain are edema and increased intracranial pressure 9. Following TBI there are microscopic alterations in biochemical and physiological pathways involving the release of excitotoxic neurotransmitters, immune mediators and oxygen radicals 10-12, which ultimately result in long-term neurological disabilities 13,14. Thus choosing appropriate animal models of TBI that present similar cellular and molecular events in human and rodent TBI is critical for studying the mechanisms underlying injury and repair. Various experimental models of TBI have been developed to reproduce aspects of TBI observed in humans, among them three specific models are widely adapted for rodents: fluid percussion, cortical impact and weight drop/impact acceleration 1. The fluid percussion device produces an injury through a craniectomy by applying a brief fluid pressure pulse on to the intact dura. The pulse is created by a pendulum striking the piston of a reservoir of fluid. The percussion produces brief displacement and deformation of neural tissue 1,15. Conversely, cortical impact injury delivers mechanical energy to the intact dura via a rigid impactor under pneumatic pressure 16,17. The weight drop/impact model is characterized by the fall of a rod with a specific mass on the closed

  7. Lateral fluid percussion: model of traumatic brain injury in mice.

    PubMed

    Alder, Janet; Fujioka, Wendy; Lifshitz, Jonathan; Crockett, David P; Thakker-Varia, Smita

    2011-08-22

    Traumatic brain injury (TBI) research has attained renewed momentum due to the increasing awareness of head injuries, which result in morbidity and mortality. Based on the nature of primary injury following TBI, complex and heterogeneous secondary consequences result, which are followed by regenerative processes (1,2). Primary injury can be induced by a direct contusion to the brain from skull fracture or from shearing and stretching of tissue causing displacement of brain due to movement (3,4). The resulting hematomas and lacerations cause a vascular response (3,5), and the morphological and functional damage of the white matter leads to diffuse axonal injury (6-8). Additional secondary changes commonly seen in the brain are edema and increased intracranial pressure (9). Following TBI there are microscopic alterations in biochemical and physiological pathways involving the release of excitotoxic neurotransmitters, immune mediators and oxygen radicals (10-12), which ultimately result in long-term neurological disabilities (13,14). Thus choosing appropriate animal models of TBI that present similar cellular and molecular events in human and rodent TBI is critical for studying the mechanisms underlying injury and repair. Various experimental models of TBI have been developed to reproduce aspects of TBI observed in humans, among them three specific models are widely adapted for rodents: fluid percussion, cortical impact and weight drop/impact acceleration (1). The fluid percussion device produces an injury through a craniectomy by applying a brief fluid pressure pulse on to the intact dura. The pulse is created by a pendulum striking the piston of a reservoir of fluid. The percussion produces brief displacement and deformation of neural tissue (1,15). Conversely, cortical impact injury delivers mechanical energy to the intact dura via a rigid impactor under pneumatic pressure (16,17). The weight drop/impact model is characterized by the fall of a rod with a specific

  8. Large-scale brain networks in affective and social neuroscience: towards an integrative functional architecture of the brain.

    PubMed

    Barrett, Lisa Feldman; Satpute, Ajay Bhaskar

    2013-06-01

    Understanding how a human brain creates a human mind ultimately depends on mapping psychological categories and concepts to physical measurements of neural response. Although it has long been assumed that emotional, social, and cognitive phenomena are realized in the operations of separate brain regions or brain networks, we demonstrate that it is possible to understand the body of neuroimaging evidence using a framework that relies on domain general, distributed structure-function mappings. We review current research in affective and social neuroscience and argue that the emerging science of large-scale intrinsic brain networks provides a coherent framework for a domain-general functional architecture of the human brain.

  9. A mathematical model of respiratory and biothermal dynamics in brain hypothermia treatment.

    PubMed

    Gaohua, Lu; Kimura, Hidenori

    2008-04-01

    Brain hypothermia treatment (BHT) requires proper mechanical ventilation and therapeutic cooling. The cooling strategy for BHT has been mainly discussed in the literature while little information is available on the respiratory management. We first developed a mathematical model that integrates the respiratory and biothermal dynamics to discuss the simultaneous managements of mechanical ventilation and therapeutic cooling. The effect of temperature on the linear approximations of hemoglobin-oxygen dissociation, together with temperature dependency of metabolism, is introduced during modeling to combine the respiratory system with the biothermal system. By comparing its transient behavior with published data, the model is verified qualitatively and then quantitatively. Second, model-based simulation of the current respiratory management in BHT suggests reduction of minute ventilation in reference to cooled brain temperature to stabilize the states of blood and brain oxygenation. Lastly, the relationship between cooling temperature and minute ventilation is approximated by a linear first-order transfer function of static gain 0.61min(-1) degrees C(-1) and time constant 8.9 h, which is used to develop a feedforward control to tune the mechanical ventilator in concert with temperature regulation of the cooling blanket. Discussion of the model encourages further studies that provide direct evidence from clinical experiments.

  10. Integrated Hydrosystem Modeling of the California Basin

    NASA Astrophysics Data System (ADS)

    Davison, J. H.; Hwang, H. T.; Sudicky, E. A.; Mallia, D.; Lin, J. C.

    2015-12-01

    The Western United States is facing one of the worst droughts on record. Climate change projections predict warmer temperatures, higher evapotranspiration rates, and no foreseeable increase in precipitation. California, in particular, has supplemented their decreased surface water supplies by mining deep groundwater. However, this supply of groundwater is limited, especially with reduced recharge. These combined factors place California's water-demanding society at dire risk. In an effort to quantify California's risks, we present a fully integrated water cycle model that captures the dynamics of the subsurface, land surface, and atmospheric domains over the entire California basin. Our water cycle model combines HydroGeoSphere (HGS), a 3-D control-volume finite element model that accommodates variably-saturated subsurface and surface water flow with evapotranspiration processes to the Weather Research and Forecasting (WRF) model, a 3-D finite difference nonhydrostatic mesoscale atmospheric simulator. The two-way coupling within our model, referred to as HGS-WRF, tightly integrates the water cycling processes by passing precipitation and potential evapotranspiration data from WRF to HGS, while exchanging actual evapotranspiration and soil saturation data from HGS to WRF. Furthermore, HGS-WRF implements a flexible coupling method that allows each model to use a unique mesh while maintaining mass conservation within and between domains. Our simulation replicated field measured evapotranspiration fluxes and showed a strong correlation between the soil saturation (depth to groundwater table) and latent heat fluxes. Altogether, the HGS-WRF California basin model is currently the most complete water resource simulation framework as it combines groundwater, surface water, the unsaturated zone, and the atmosphere into one coupled system.

  11. Integrated identification, modeling and control with applications

    NASA Astrophysics Data System (ADS)

    Shi, Guojun

    This thesis deals with the integration of system design, identification, modeling and control. In particular, six interdisciplinary engineering problems are addressed and investigated. Theoretical results are established and applied to structural vibration reduction and engine control problems. First, the data-based LQG control problem is formulated and solved. It is shown that a state space model is not necessary to solve this problem; rather a finite sequence from the impulse response is the only model data required to synthesize an optimal controller. The new theory avoids unnecessary reliance on a model, required in the conventional design procedure. The infinite horizon model predictive control problem is addressed for multivariable systems. The basic properties of the receding horizon implementation strategy is investigated and the complete framework for solving the problem is established. The new theory allows the accommodation of hard input constraints and time delays. The developed control algorithms guarantee the closed loop stability. A closed loop identification and infinite horizon model predictive control design procedure is established for engine speed regulation. The developed algorithms are tested on the Cummins Engine Simulator and desired results are obtained. A finite signal-to-noise ratio model is considered for noise signals. An information quality index is introduced which measures the essential information precision required for stabilization. The problems of minimum variance control and covariance control are formulated and investigated. Convergent algorithms are developed for solving the problems of interest. The problem of the integrated passive and active control design is addressed in order to improve the overall system performance. A design algorithm is developed, which simultaneously finds: (i) the optimal values of the stiffness and damping ratios for the structure, and (ii) an optimal output variance constrained stabilizing

  12. Normal brain ageing: models and mechanisms

    PubMed Central

    Toescu, Emil C

    2005-01-01

    Normal ageing is associated with a degree of decline in a number of cognitive functions. Apart from the issues raised by the current attempts to expand the lifespan, understanding the mechanisms and the detailed metabolic interactions involved in the process of normal neuronal ageing continues to be a challenge. One model, supported by a significant amount of experimental evidence, views the cellular ageing as a metabolic state characterized by an altered function of the metabolic triad: mitochondria–reactive oxygen species (ROS)–intracellular Ca2+. The perturbation in the relationship between the members of this metabolic triad generate a state of decreased homeostatic reserve, in which the aged neurons could maintain adequate function during normal activity, as demonstrated by the fact that normal ageing is not associated with widespread neuronal loss, but become increasingly vulnerable to the effects of excessive metabolic loads, usually associated with trauma, ischaemia or neurodegenerative processes. This review will concentrate on some of the evidence showing altered mitochondrial function with ageing and also discuss some of the functional consequences that would result from such events, such as alterations in mitochondrial Ca2+ homeostasis, ATP production and generation of ROS. PMID:16321805

  13. Hypnosis, suggestion, and suggestibility: an integrative model.

    PubMed

    Lynn, Steven Jay; Laurence, Jean-Roch; Kirsch, Irving

    2015-01-01

    This article elucidates an integrative model of hypnosis that integrates social, cultural, cognitive, and neurophysiological variables at play both in and out of hypnosis and considers their dynamic interaction as determinants of the multifaceted experience of hypnosis. The roles of these variables are examined in the induction and suggestion stages of hypnosis, including how they are related to the experience of involuntariness, one of the hallmarks of hypnosis. It is suggested that studies of the modification of hypnotic suggestibility; cognitive flexibility; response sets and expectancies; the default-mode network; and the search for the neurophysiological correlates of hypnosis, more broadly, in conjunction with research on social psychological variables, hold much promise to further understanding of hypnosis.

  14. Performance of an INTEGRAL spectrometer model

    NASA Technical Reports Server (NTRS)

    Jean, P.; Naya, J. E.; vonBallmoos, P.; Vedrenne, G.; Teegarden, B.

    1997-01-01

    Model calculations for the INTEGRAL spectrometer (SPI) onboard the future INTErnational Gamma Ray Astrophysics Laboratory (INTEGAL) are presented, where the sensitivity for narrow lines is based on estimates of the background level and the detection efficiency. The instrumental background rates are explained as the sum of various components that depend on the cosmic ray intensity and the spectrometer characteristics, such as the mass distribution around the Ge detectors, the passive material, the characteristics of the detector system and the background reduction techniques. Extended background calculations were performed with Monte Carlo simulations and using semi-empirical and calculated neutron and proton cross sections. In order to improve the INTEGRAL spectrometer sensitivity, several designs and background reduction techniques were compared for an instrument with a fixed detector volume.

  15. Towards an integrative model of sociality in caviomorph rodents

    PubMed Central

    Hayes, Loren D.; Burger, Joseph Robert; Soto-Gamboa, Mauricio; Sobrero, Raúl; Ebensperger, Luis A

    2012-01-01

    In the late 1990s and early 2000s it was recognized that behavioral ecologists needed to study the sociality of caviomorph rodents (New World hystricognaths) before generalizations about rodent sociality could be made. Researchers identified specific problems facing individuals interested in caviomorph sociality, including a lack of information on the proximate mechanisms of sociality, role of social environment in development, and geographical or intraspecific variation in social systems. Since then researchers have described the social systems of many previously understudied species, including some with broad geographical ranges. Researchers have done a good job of determining the role of social environments in development and identifying the costs and benefits of social living. However, relatively little is known about the proximate mechanisms of social behavior and fitness consequences, limiting progress toward the development of integrative (evolutionary-mechanistic) models for sociality. To develop integrative models behavioral ecologists studying caviomorph rodents must generate information on the fitness consequences of different types of social organization, brain mechanisms, and endocrine substrates of sociality. We review our current understanding and future directions for research in these conceptual areas. A greater understanding of disease ecology, particularly in species carrying Old World parasites, is needed before we can identify potential links between social phenotypes, mechanism, and fitness. PMID:22328791

  16. Data-driven forward model inference for EEG brain imaging.

    PubMed

    Hansen, Sofie Therese; Hauberg, Søren; Hansen, Lars Kai

    2016-06-13

    Electroencephalography (EEG) is a flexible and accessible tool with excellent temporal resolution but with a spatial resolution hampered by volume conduction. Reconstruction of the cortical sources of measured EEG activity partly alleviates this problem and effectively turns EEG into a brain imaging device. The quality of the source reconstruction depends on the forward model which details head geometry and conductivities of different head compartments. These person-specific factors are complex to determine, requiring detailed knowledge of the subject's anatomy and physiology. In this proof-of-concept study, we show that, even when anatomical knowledge is unavailable, a suitable forward model can be estimated directly from the EEG. We propose a data-driven approach that provides a low-dimensional parametrization of head geometry and compartment conductivities, built using a corpus of forward models. Combined with only a recorded EEG signal, we are able to estimate both the brain sources and a person-specific forward model by optimizing this parametrization. We thus not only solve an inverse problem, but also optimize over its specification. Our work demonstrates that personalized EEG brain imaging is possible, even when the head geometry and conductivities are unknown.

  17. A Novel Mouse Model of Penetrating Brain Injury

    PubMed Central

    Cernak, Ibolja; Wing, Ian D.; Davidsson, Johan; Plantman, Stefan

    2014-01-01

    Penetrating traumatic brain injury (pTBI) has been difficult to model in small laboratory animals, such as rats or mice. Previously, we have established a non-fatal, rat model for pTBI using a modified air-rifle that accelerates a pellet, which hits a small probe that then penetrates the experimental animal’s brain. Knockout and transgenic strains of mice offer attractive tools to study biological reactions induced by TBI. Hence, in the present study, we adapted and modified our model to be used with mice. The technical characterization of the impact device included depth and speed of impact, as well as dimensions of the temporary cavity formed in a brain surrogate material after impact. Biologically, we have focused on three distinct levels of severity (mild, moderate, and severe), and characterized the acute phase response to injury in terms of tissue destruction, neural degeneration, and gliosis. Functional outcome was assessed by measuring bodyweight and motor performance on rotarod. The results showed that this model is capable of reproducing major morphological and neurological changes of pTBI; as such, we recommend its utilization in research studies aiming to unravel the biological events underlying injury and regeneration after pTBI. PMID:25374559

  18. Multidimensional integrable models of gravitation and cosmology

    NASA Astrophysics Data System (ADS)

    Ivashchuk, V. D.; Melnikov, V. N.

    Review of the motivation and main results in multidimentional gravitation and cosmology is presented. Special attention is devoted to results within the model with scalar fields and fields of forms in the billiard approach for obtaining cosmological solutions with branes and integrable configurations with fluxand black branes. In case of the quantum billiard with branes it is shown that the basis solutions for wave functions vanish in the limit of the formation of billiard walls (i.e., at the singularity) for the D = 11 model which mimics the D = 11 supergravitational cosmology. Another fruitful approach - to multidimensional gravity with higher derivatives is mentioned, which leads to a unified description of inflation and the present accelerated expansion of the Universe. Some of these models explain possible spatial and temporal variations of the fine structure and the gravitational constants.

  19. Integrated modeling of the Euro50

    NASA Astrophysics Data System (ADS)

    Andersen, Torben E.; Browne, Michael T.; Enmark, Anita; Moraru, Dan; Owner-Petersen, Mette; Riewaldt, Holger

    2004-07-01

    The Euro50 is a proposed 50 m optical and infrared telescope. It will have thousands of control loops to keep the optics aligned under influence of wind, gravity and thermal loads. Cross-disciplinary integrated modeling is used to study the overall performance of the Euro50. A sub-model of the mechanical structure originates from finite element modeling. The optical performance is determined using ray tracing, both non-linear and linearized. The primary mirror segment alignment control system is modeled with the 618 segments taken as rigid bodies. Adaptive optics is included using a layered model of the atmosphere and sub-models of the wavefront sensor, reconstructor and controller. The deformable mirror is, so far, described by a simple influence function and a second order dynamical transfer function but more detailed work is in progress. The model has been implemented using Matlab/Simulink on individual computers but it will shortly be implemented on a Beowulf cluster within a trusted network. Communication routines between Matlab on the cluster processors have been written and are being benchmarked. Representative results from the simulations are shown.

  20. Theoretical Compartment Modeling of DCE-MRI Data Based on the Transport across Physiological Barriers in the Brain

    PubMed Central

    Fanea, Laura; David, Leontin I.; Lebovici, Andrei; Carbone, Francesca; Sfrangeu, Silviu A.

    2012-01-01

    Neurological disorders represent major causes of lost years of healthy life and mortality worldwide. Development of their quantitative interdisciplinary in vivo evaluation is required. Compartment modeling (CM) of brain data acquired in vivo using magnetic resonance imaging techniques with clinically available contrast agents can be performed to quantitatively assess brain perfusion. Transport of 1H spins in water molecules across physiological compartmental brain barriers in three different pools was mathematically modeled and theoretically evaluated in this paper and the corresponding theoretical compartment modeling of dynamic contrast enhanced magnetic resonance imaging (DCE-MRI) data was analyzed. The pools considered were blood, tissue, and cerebrospinal fluid (CSF). The blood and CSF data were mathematically modeled assuming continuous flow of the 1H spins in these pools. Tissue data was modeled using three CMs. Results in this paper show that transport across physiological brain barriers such as the blood to brain barrier, the extracellular space to the intracellular space barrier, or the blood to CSF barrier can be evaluated quantitatively. Statistical evaluations of this quantitative information may be performed to assess tissue perfusion, barriers' integrity, and CSF flow in vivo in the normal or disease-affected brain or to assess response to therapy. PMID:22666304

  1. WHITE MATTER INTEGRITY IN TRAUMATIC BRAIN INJURY: EFFECTS OF PERMISSIBLE FIBER TURNING ANGLE

    PubMed Central

    Dennis, Emily L.; Jin, Yan; Kernan, Claudia; Babikian, Talin; Mink, Richard; Babbitt, Christopher; Johnson, Jeffrey; Giza, Christopher C.; Asarnow, Robert F.; Thompson, Paul M.

    2015-01-01

    Traumatic brain injury (TBI) is the leading cause of death and disability in children. Diffusion weighted imaging (DWI) methods have been shown to be especially sensitive to white matter abnormalities in TBI. We used our newly developed autoMATE algorithm (automated multi-atlas tract extraction) to map altered WM integrity in TBI. Even so, tractography methods include a free parameter that limits the maximum permissible turning angles for extracted fibers, with little investigation of how this may affect statistical group comparisons. Here, we examined WM integrity calculated over a range of fiber turning angles to determine to what extent this parameter affects our ability to detect group differences. Fiber turning angle threshold has a subtle, but sometimes significant, effect on the differences we were able to detect between TBI and healthy children. PMID:26413206

  2. Callosal Function in Pediatric Traumatic Brain Injury Linked to Disrupted White Matter Integrity

    PubMed Central

    Dennis, Emily L.; Ellis, Monica U.; Marion, Sarah D.; Jin, Yan; Moran, Lisa; Olsen, Alexander; Kernan, Claudia; Babikian, Talin; Mink, Richard; Babbitt, Christopher; Johnson, Jeffrey; Giza, Christopher C.; Asarnow, Robert F.

    2015-01-01

    Traumatic brain injury (TBI) often results in traumatic axonal injury and white matter (WM) damage, particularly to the corpus callosum (CC). Damage to the CC can lead to impaired performance on neurocognitive tasks, but there is a high degree of heterogeneity in impairment following TBI. Here we examined the relation between CC microstructure and function in pediatric TBI. We used high angular resolution diffusion-weighted imaging (DWI) to evaluate the structural integrity of the CC in humans following brain injury in a sample of 32 children (23 males and 9 females) with moderate-to-severe TBI (msTBI) at 1–5 months postinjury, compared with well matched healthy control children. We assessed CC function through interhemispheric transfer time (IHTT) as measured using event-related potentials (ERPs), and related this to DWI measures of WM integrity. Finally, the relation between DWI and IHTT results was supported by additional results of neurocognitive performance assessed using a single composite performance scale. Half of the msTBI participants (16 participants) had significantly slower IHTTs than the control group. This slow IHTT group demonstrated lower CC integrity (lower fractional anisotropy and higher mean diffusivity) and poorer neurocognitive functioning than both the control group and the msTBI group with normal IHTTs. Lower fractional anisotropy—a common sign of impaired WM—and slower IHTTs also predicted poor neurocognitive function. This study reveals that there is a subset of pediatric msTBI patients during the post-acute phase of injury who have markedly impaired CC functioning and structural integrity that is associated with poor neurocognitive functioning. SIGNIFICANCE STATEMENT Traumatic brain injury (TBI) is the primary cause of death and disability in children and adolescents. There is considerable heterogeneity in postinjury outcome, which is only partially explained by injury severity. Imaging biomarkers may help explain some of this

  3. Genetic mouse models of brain ageing and Alzheimer's disease.

    PubMed

    Bilkei-Gorzo, Andras

    2014-05-01

    Progression of brain ageing is influenced by a complex interaction of genetic and environmental factors. Analysis of genetically modified animals with uniform genetic backgrounds in a standardised, controlled environment enables the dissection of critical determinants of brain ageing on a molecular level. Human and animal studies suggest that increased load of damaged macromolecules, efficacy of DNA maintenance, mitochondrial activity, and cellular stress defences are critical determinants of brain ageing. Surprisingly, mouse lines with genetic impairment of anti-oxidative capacity generally did not show enhanced cognitive ageing but rather an increased sensitivity to oxidative challenge. Mouse lines with impaired mitochondrial activity had critically short life spans or severe and rapidly progressing neurodegeneration. Strains with impaired clearance in damaged macromolecules or defects in the regulation of cellular stress defences showed alterations in the onset and progression of cognitive decline. Importantly, reduced insulin/insulin-like growth factor signalling generally increased life span but impaired cognitive functions revealing a complex interaction between ageing of the brain and of the body. Brain ageing is accompanied by an increased risk of developing Alzheimer's disease. Transgenic mouse models expressing high levels of mutant human amyloid precursor protein showed a number of symptoms and pathophysiological processes typical for early phase of Alzheimer's disease. Generally, therapeutic strategies effective against Alzheimer's disease in humans were also active in the Tg2576, APP23, APP/PS1 and 5xFAD lines, but a large number of false positive findings were also reported. The 3xtg AD model likely has the highest face and construct validity but further studies are needed.

  4. Intrastriatal Delivery of Integration-Deficient Lentiviral Vectors in a Rat Model of Parkinson's Disease.

    PubMed

    Lu-Nguyen, Ngoc B; Broadstock, Martin; Yáñez-Muñoz, Rafael J

    2016-01-01

    Standard integration-proficient lentiviral vectors (IPLVs) are effective at much lower doses than other vector systems and have shown promise in several gene therapy approaches. Their main drawback is the potential risk of insertional mutagenesis. Novel biosafety-enhanced integration-deficient lentiviral vectors (IDLVs) offer a significant improvement and comparable transduction efficacy to their integrating counterparts in some central nervous system applications. We describe here methods for (1) production of IDLVs (and IPLVs), (2) IDLV/IPLV delivery into the striatum of a rat model of Parkinson's disease, and (3) postmortem brain processing.

  5. Self-organization in a simple brain model

    SciTech Connect

    Stassinopoulos, D.; Bak, P.; Alstroem, P.

    1994-03-10

    Simulations on a simple model of the brain are presented. The model consists of a set of randomly connected neurons. Inputs and outputs are also connected randomly to a subset of neurons. For each input there is a set of output neurons which must fire in order to achieve success. A signal giving information as to whether or not the action was successful is fed back to the brain from the environment. The connections between firing neurons are strengthened or weakened according to whether or not the action was successful. The system learns, through a self-organization process, to react intelligently to input signals, i.e. it learns to quickly select the correct output for each input. If part of the network is damaged, the system relearns the correct response after a training period.

  6. Androgen modulation of social decision-making mechanisms in the brain: an integrative and embodied perspective.

    PubMed

    Oliveira, Gonçalo A; Oliveira, Rui F

    2014-01-01

    Apart from their role in reproduction androgens also respond to social challenges and this response has been seen as a way to regulate the expression of behavior according to the perceived social environment (Challenge hypothesis, Wingfield et al., 1990). This hypothesis implies that social decision-making mechanisms localized in the central nervous system (CNS) are open to the influence of peripheral hormones that ultimately are under the control of the CNS through the hypothalamic-pituitary-gonadal axis. Therefore, two puzzling questions emerge at two different levels of biological analysis: (1) Why does the brain, which perceives the social environment and regulates androgen production in the gonad, need feedback information from the gonad to adjust its social decision-making processes? (2) How does the brain regulate gonadal androgen responses to social challenges and how do these feedback into the brain? In this paper, we will address these two questions using the integrative approach proposed by Niko Tinbergen, who proposed that a full understanding of behavior requires its analysis at both proximate (physiology, ontogeny) and ultimate (ecology, evolution) levels.

  7. Androgen modulation of social decision-making mechanisms in the brain: an integrative and embodied perspective

    PubMed Central

    Oliveira, Gonçalo A.; Oliveira, Rui F.

    2014-01-01

    Apart from their role in reproduction androgens also respond to social challenges and this response has been seen as a way to regulate the expression of behavior according to the perceived social environment (Challenge hypothesis, Wingfield et al., 1990). This hypothesis implies that social decision-making mechanisms localized in the central nervous system (CNS) are open to the influence of peripheral hormones that ultimately are under the control of the CNS through the hypothalamic-pituitary-gonadal axis. Therefore, two puzzling questions emerge at two different levels of biological analysis: (1) Why does the brain, which perceives the social environment and regulates androgen production in the gonad, need feedback information from the gonad to adjust its social decision-making processes? (2) How does the brain regulate gonadal androgen responses to social challenges and how do these feedback into the brain? In this paper, we will address these two questions using the integrative approach proposed by Niko Tinbergen, who proposed that a full understanding of behavior requires its analysis at both proximate (physiology, ontogeny) and ultimate (ecology, evolution) levels. PMID:25100938

  8. 77 FR 13578 - Disability and Rehabilitation Research Project; Traumatic Brain Injury Model Systems Centers

    Federal Register 2010, 2011, 2012, 2013, 2014

    2012-03-07

    ... Disability and Rehabilitation Research Project; Traumatic Brain Injury Model Systems Centers AGENCY: Office... Brain Injury Model Systems Centers. CFDA Number: 84.133A-5. SUMMARY: The Assistant Secretary for Special... Projects (DRRPs) to serve as Traumatic Brain Injury Model Systems (TBIMS) Centers. The Assistant...

  9. The Effects of a High-Energy Diet on Hippocampal Function and Blood-Brain Barrier Integrity in the Rat

    PubMed Central

    Kanoski, Scott E.; Zhang, Yanshu; Zheng, Wei; Davidson, Terry L.

    2016-01-01

    Cognitive impairment and Alzheimer’s Disease are linked with intake of a Western Diet, characterized by high levels of saturated fats and simple carbohydrates. In rats, these dietary components have been shown to disrupt hippocampal-dependent learning and memory processes, particularly those involving spatial memory. Using a rat model, the present research assessed the degree to which consumption of a high-energy (HE) diet, similar to those found in modern Western cultures, produces a selective impairment in hippocampal function as opposed to a more global cognitive disruption. Learning and memory performance was examined following 90-days consumption of an HE-diet in three nonspatial discrimination learning problems that differed with respect to their dependence on the integrity of the hippocampus. The results showed that consumption of the HE-diet impaired performance in a hippocampal-dependent feature negative discrimination problem relative to chow-fed controls, whereas performance was spared on two discrimination problems that do not rely on the hippocampus. To explore the mechanism whereby consuming HE-diets impairs cognitive function, we investigated the effect of HE-diets on the integrity of the blood-brain barrier (BBB). We found that HE-diet consumption produced a decrease in mRNA expression of tight junction proteins, particularly Claudin-5 and -12, in the choroid plexus and the BBB. Consequently, an increased blood-to-brain permeability of sodium fluorescein was observed in the hippocampus, but not in the striatum and prefrontal cortex following HE-diet access. There results indicate that hippocampal function may be particularly vulnerable to disruption by HE-diets, and this disruption may be related to impaired BBB integrity. PMID:20413889

  10. Integrated research in constitutive modelling at elevated temperatures, part 1

    NASA Technical Reports Server (NTRS)

    Haisler, W. E.; Allen, D. H.

    1986-01-01

    Topics covered include: numerical integration techniques; thermodynamics and internal state variables; experimental lab development; comparison of models at room temperature; comparison of models at elevated temperature; and integrated software development.

  11. TOWARD EFFICIENT RIPARIAN RESTORATION: INTEGRATING ECONOMIC, PHYSICAL, AND BIOLOGICAL MODELS

    EPA Science Inventory

    This paper integrates economic, biological, and physical models to determine the efficient combination and spatial allocation of conservation efforts for water quality protection and salmonid habitat enhancement in the Grande Ronde basin, Oregon. The integrated modeling system co...

  12. Integrated pollutant removal: modeling and experimentation

    SciTech Connect

    Ochs, Thomas L.; Oryshchyn, Danylo B.; Summers, Cathy A.

    2005-01-01

    Experimental and computational work at the Albany Research Center, USDOE is investigating an integrated pollutant removal (IPR) process which removes all pollutants from flue gas, including SOX, NOX, particulates, CO2, and Hg. In combination with flue gas recirculation, heat recovery, and oxy-fuel combustion, the process produces solid, gas, and liquid waste streams. The gas exhaust stream comprises O2 and N2. Liquid streams contain H2O, SOX, NOX, and CO2. Computer modeling and low to moderate pressure experimentation are defining system chemistry with respect to SOX and H2O as well as heat and mass transfer for the IPR process.

  13. Opioid Abuse after Traumatic Brain Injury: Evaluation Using Rodent Models

    DTIC Science & Technology

    2015-09-01

    neurological changes that increase vulnerability for drug abuse and addiction. Consequently, we have been evaluating the effects of TBI on both the...rewarding effects of opioid drugs as well as the development of tolerance and physical dependence in well-established rat models of abuse-related drug ...brain injured rats have a greater sensitivity to the rewarding effects of oxycodone and will self-administer greater total doses of drug compared to

  14. Social competence in pediatric brain tumor survivors: application of a model from social neuroscience and developmental psychology.

    PubMed

    Hocking, Matthew C; McCurdy, Mark; Turner, Elise; Kazak, Anne E; Noll, Robert B; Phillips, Peter; Barakat, Lamia P

    2015-03-01

    Pediatric brain tumor (BT) survivors are at risk for psychosocial late effects across many domains of functioning, including neurocognitive and social. The literature on the social competence of pediatric BT survivors is still developing and future research is needed that integrates developmental and cognitive neuroscience research methodologies to identify predictors of survivor social adjustment and interventions to ameliorate problems. This review discusses the current literature on survivor social functioning through a model of social competence in childhood brain disorder and suggests future directions based on this model. Interventions pursuing change in survivor social adjustment should consider targeting social ecological factors.

  15. A hierarchical coherent-gene-group model for brain development.

    PubMed

    Tsigelny, I F; Kouznetsova, V L; Baitaluk, M; Changeux, J-P

    2013-03-01

    We have described a strategy to analyze the data available on brain genes expression, using the concept of coherent-gene groups controlled by transcription factors (TFs). A hierarchical model of gene-expression patterns during brain development was established that identified the genes assumed to behave as functionally coding. Analysis of the concerned signaling pathways and processes showed distinct temporal gene-expression patterns in relation with neurogenesis/synaptogenesis. We identified the hierarchical tree of TF networks that determined the patterns of genes expressed during brain development. Some 'master TFs' at the top level of the hierarchy regulated the expression of gene groups. Enhanced/decreased activity of a few master TFs may explain paradoxes raised by the genetic determination of autism-spectrum disorders and schizophrenia. Our analysis showed gene-TF networks, common or related, to these disorders that exhibited two maxima of expression, one in the prenatal and the other at early postnatal period of development, consistent with the view that these disorders originate in the prenatal period, develop in the postnatal period, and reach the ultimate neural and behavioral phenotype with different sets of genes regulating each of these periods. We proposed a strategy for drug design based upon the temporal patterns of expression of the concerned TFs. Ligands targeting specific TFs can be designed to specifically affect the pathological evolution of the mutated gene(s) in genetically predisposed patients when administered at relevant stages of brain development.

  16. A model for genomic imprinting in the social brain: juveniles.

    PubMed

    Ubeda, Francisco; Gardner, Andy

    2010-09-01

    What are imprinted genes doing in the adult brain? Genomic imprinting is when a gene's expression depends upon parent of origin. According to the prevailing view, the "kinship theory" of genomic imprinting, this effect is driven by evolutionary conflicts between genes inherited via sperm versus egg. This theory emphasizes conflicts over the allocation of maternal resources, and focuses upon genes that are expressed in the placenta and infant brain. However, there is growing evidence that imprinted genes are also expressed in the juvenile and adult brain, after cessation of parental care. These genes have recently been suggested to underpin neurological disorders of the social brain such as psychosis and autism. Here we advance the kinship theory by developing an evolutionary model of genomic imprinting for social behavior beyond the nuclear family. We consider the role of demography and mating system, emphasizing the importance of sex differences in dispersal and variance in reproductive success. We predict that, in hominids and birds, altruism will be promoted by paternally inherited genes and egoism will be promoted by maternally inherited genes. In nonhominid mammals we predict more diversity, with some mammals showing the same pattern and other showing the reverse. We discuss the implications for the evolution of psychotic and autistic spectrum disorders in human populations with different social structures.

  17. Early Shifts of Brain Metabolism by Caloric Restriction Preserve White Matter Integrity and Long-Term Memory in Aging Mice.

    PubMed

    Guo, Janet; Bakshi, Vikas; Lin, Ai-Ling

    2015-01-01

    Preservation of brain integrity with age is highly associated with lifespan determination. Caloric restriction (CR) has been shown to increase longevity and healthspan in various species; however, its effects on preserving living brain functions in aging remain largely unexplored. In the study, we used multimodal, non-invasive neuroimaging (PET/MRI/MRS) to determine in vivo brain glucose metabolism, energy metabolites, and white matter structural integrity in young and old mice fed with either control or 40% CR diet. In addition, we determined the animals' memory and learning ability with behavioral assessments. Blood glucose, blood ketone bodies, and body weight were also measured. We found distinct patterns between normal aging and CR aging on brain functions - normal aging showed reductions in brain glucose metabolism, white matter integrity, and long-term memory, resembling human brain aging. CR aging, in contrast, displayed an early shift from glucose to ketone bodies metabolism, which was associated with preservations of brain energy production, white matter integrity, and long-term memory in aging mice. Among all the mice, we found a positive correlation between blood glucose level and body weight, but an inverse association between blood glucose level and lifespan. Our findings suggest that CR could slow down brain aging, in part due to the early shift of energy metabolism caused by lower caloric intake, and we were able to identify the age-dependent effects of CR non-invasively using neuroimaging. These results provide a rationale for CR-induced sustenance of brain health with extended longevity.

  18. Early Shifts of Brain Metabolism by Caloric Restriction Preserve White Matter Integrity and Long-Term Memory in Aging Mice

    PubMed Central

    Guo, Janet; Bakshi, Vikas; Lin, Ai-Ling

    2015-01-01

    Preservation of brain integrity with age is highly associated with lifespan determination. Caloric restriction (CR) has been shown to increase longevity and healthspan in various species; however, its effects on preserving living brain functions in aging remain largely unexplored. In the study, we used multimodal, non-invasive neuroimaging (PET/MRI/MRS) to determine in vivo brain glucose metabolism, energy metabolites, and white matter structural integrity in young and old mice fed with either control or 40% CR diet. In addition, we determined the animals’ memory and learning ability with behavioral assessments. Blood glucose, blood ketone bodies, and body weight were also measured. We found distinct patterns between normal aging and CR aging on brain functions – normal aging showed reductions in brain glucose metabolism, white matter integrity, and long-term memory, resembling human brain aging. CR aging, in contrast, displayed an early shift from glucose to ketone bodies metabolism, which was associated with preservations of brain energy production, white matter integrity, and long-term memory in aging mice. Among all the mice, we found a positive correlation between blood glucose level and body weight, but an inverse association between blood glucose level and lifespan. Our findings suggest that CR could slow down brain aging, in part due to the early shift of energy metabolism caused by lower caloric intake, and we were able to identify the age-dependent effects of CR non-invasively using neuroimaging. These results provide a rationale for CR-induced sustenance of brain health with extended longevity. PMID:26617514

  19. The Integrated Airport Competition Model, 1998

    NASA Technical Reports Server (NTRS)

    Veldhuis, J.; Essers, I.; Bakker, D.; Cohn, N.; Kroes, E.

    1999-01-01

    This paper addresses recent model development by the Directorate General of Civil Aviation (DGCA) and Hague Consulting Group (HCG) concerning long-distance travel. Long-distance travel demand is growing very quickly and raising a great deal of economic and policy issues. There is increasing competition among the main Western European airports, and smaller, regional airports are fighting for market share. New modes of transport, such as high speed rail, are also coming into the picture and affect the mode split for medium distance transport within Europe. Developments such as these are demanding the attention of policy makers and a tool is required for their analysis. For DGCA, Hague Consulting Group has developed a model system to provide answers to the policy questions posed by these expected trends, and to identify areas where policy makers can influence the traveller choices. The development of this model system, the Integrated Airport Competition Model/integraal Luchthaven Competitie Model (ILCM), began in 1992. Since that time the sub-models, input data and user interface have been expanded, updated and improved. HCG and DGCA have transformed the ILCM from a prototype into an operational forecasting tool.

  20. Integrated Modeling of Complex Optomechanical Systems

    NASA Astrophysics Data System (ADS)

    Andersen, Torben; Enmark, Anita

    2011-09-01

    Mathematical modeling and performance simulation are playing an increasing role in large, high-technology projects. There are two reasons; first, projects are now larger than they were before, and the high cost calls for detailed performance prediction before construction. Second, in particular for space-related designs, it is often difficult to test systems under realistic conditions beforehand, and mathematical modeling is then needed to verify in advance that a system will work as planned. Computers have become much more powerful, permitting calculations that were not possible before. At the same time mathematical tools have been further developed and found acceptance in the community. Particular progress has been made in the fields of structural mechanics, optics and control engineering, where new methods have gained importance over the last few decades. Also, methods for combining optical, structural and control system models into global models have found widespread use. Such combined models are usually called integrated models and were the subject of this symposium. The objective was to bring together people working in the fields of groundbased optical telescopes, ground-based radio telescopes, and space telescopes. We succeeded in doing so and had 39 interesting presentations and many fruitful discussions during coffee and lunch breaks and social arrangements. We are grateful that so many top ranked specialists found their way to Kiruna and we believe that these proceedings will prove valuable during much future work.

  1. A Population Model of Integrative Cardiovascular Physiology

    PubMed Central

    Pruett, William A.; Husband, Leland D.; Husband, Graham; Dakhlalla, Muhammad; Bellamy, Kyle; Coleman, Thomas G.; Hester, Robert L.

    2013-01-01

    We present a small integrative model of human cardiovascular physiology. The model is population-based; rather than using best fit parameter values, we used a variant of the Metropolis algorithm to produce distributions for the parameters most associated with model sensitivity. The population is built by sampling from these distributions to create the model coefficients. The resulting models were then subjected to a hemorrhage. The population was separated into those that lost less than 15 mmHg arterial pressure (compensators), and those that lost more (decompensators). The populations were parametrically analyzed to determine baseline conditions correlating with compensation and decompensation. Analysis included single variable correlation, graphical time series analysis, and support vector machine (SVM) classification. Most variables were seen to correlate with propensity for circulatory collapse, but not sufficiently to effect reasonable classification by any single variable. Time series analysis indicated a single significant measure, the stressed blood volume, as predicting collapse in situ, but measurement of this quantity is clinically impossible. SVM uncovered a collection of variables and parameters that, when taken together, provided useful rubrics for classification. Due to the probabilistic origins of the method, multiple classifications were attempted, resulting in an average of 3.5 variables necessary to construct classification. The most common variables used were systemic compliance, baseline baroreceptor signal strength and total peripheral resistance, providing predictive ability exceeding 90%. The methods presented are suitable for use in any deterministic mathematical model. PMID:24058546

  2. INTEGRATED SPEED ESTIMATION MODEL FOR MULTILANE EXPREESSWAYS

    NASA Astrophysics Data System (ADS)

    Hong, Sungjoon; Oguchi, Takashi

    In this paper, an integrated speed-estimation model is developed based on empirical analyses for the basic sections of intercity multilane expressway un der the uncongested condition. This model enables a speed estimation for each lane at any site under arb itrary highway-alignment, traffic (traffic flow and truck percentage), and rainfall conditions. By combin ing this model and a lane-use model which estimates traffic distribution on the lanes by each vehicle type, it is also possible to es timate an average speed across all the lanes of one direction from a traffic demand by vehicle type under specific highway-alignment and rainfall conditions. This model is exp ected to be a tool for the evaluation of traffic performance for expressways when the performance me asure is travel speed, which is necessary for Performance-Oriented Highway Planning and Design. Regarding the highway-alignment condition, two new estimators, called effective horizo ntal curvature and effective vertical grade, are proposed in this paper which take into account the influence of upstream and downstream alignment conditions. They are applied to the speed-estimation model, and it shows increased accuracy of the estimation.

  3. Developing Metrics in Systems Integration (ISS Program COTS Integration Model)

    NASA Technical Reports Server (NTRS)

    Lueders, Kathryn

    2007-01-01

    This viewgraph presentation reviews some of the complications in developing metrics for systems integration. Specifically it reviews a case study of how two programs within NASA try to develop and measure performance while meeting the encompassing organizational goals.

  4. Treatment of pathological gambling - integrative systemic model.

    PubMed

    Mladenović, Ivica; Lažetić, Goran; Lečić-Toševski, Dušica; Dimitrijević, Ivan

    2015-03-01

    Pathological gambling was classified under impulse control disorders within the International Classification of Diseases (ICD-10) (WHO 1992), but the most recent Diagnostic and Statistical Manual, 5th edition (DSM-V), (APA 2013), has recognized pathological gambling as a first disorder within a new diagnostic category of behavioral addictions - Gambling disorder. Pathological gambling is a disorder in progression, and we hope that our experience in the treatment of pathological gambling in the Daily Hospital for Addictions at The Institute of Mental Health, through the original "Integrative - systemic model" would be of use to colleagues, dealing with this pathology. This model of treatment of pathological gambling is based on multi-systemic approach and it primarily represents an integration of family and cognitive-behavioral therapy, with traces of psychodynamic, existential and pharmacotherapy. The model is based on the book "Pathological gambling - with self-help manual" by Dr Mladenovic and Dr Lazetic, and has been designed in the form of a program that lasts 10 weeks in the intensive phase, and then continues for two years in the form of "extended treatment" ("After care"). The intensive phase is divided into three segments: educational, insight with initial changes and analysis of the achieved changes with the definition of plans and areas that need to be addressed in the extended treatment. "Extended treatment" lasts for two years in the form of group therapy, during which there is a second order change of the identified patient, but also of other family members. Pathological gambling has been treated in the form of systemic-family therapy for more than 10 years at the Institute of Mental Health (IMH), in Belgrade. For second year in a row the treatment is carried out by the modern "Integrative-systemic model". If abstinence from gambling witihin the period of one year after completion of the intensive phase of treatment is taken as the main criterion of

  5. 2-Methoxystypandrone ameliorates brain function through preserving BBB integrity and promoting neurogenesis in mice with acute ischemic stroke.

    PubMed

    Chern, Chang-Ming; Wang, Yea-Hwey; Liou, Kuo-Tong; Hou, Yu-Chang; Chen, Chien-Chih; Shen, Yuh-Chiang

    2014-02-01

    2-Methoxystypandrone (2-MS), a naphthoquinone, has been shown to display an immunomodulatory effect in a cellular model. To explore whether 2-MS could protect mice against cerebral ischemic/reperfusion (I/R)-induced brain injury, we evaluated 2-MS's protective effects on an acute ischemic stroke by inducing a middle cerebral artery occlusion/reperfusion (MCAO) injury in murine model. Treatment of mice that have undergone I/R injury with 2-MS (10-100 μg/kg, i.v.) at 2 h after MCAO enhanced survival rate and ameliorated neurological deficits, brain infarction, neural dysfunction and massive oxidative stress, due to an enormous production of free radicals and breakdown of blood-brain barrier (BBB) by I/R injury; this primarily occurred with extensive infiltration of CD11b-positive inflammatory cells and upexpression of inducible nitric oxide synthase (iNOS), cyclooxygenase-2 and p65 nuclear factor-kappa B (NF-κB). All of these pathological changes were diminished by 2-MS; 2-MS also intensively limited cortical infarction and promoted upexpression of neurodevelopmental genes near peri-infarct cortex and endogenous neurogenesis near subgranular zone of hippocampal dentate gyrus and the subventricular zone, most possibly by inactivation of GSK3β which in turn upregulating β-catenin, Bcl-2 adam11 and adamts20. We conclude that 2-MS blocks inflammatory responses by impairing NF-κB signaling to limit the inflammation and oxidative stress for preservation of BBB integrity; 2-MS also concomitantly promotes neurodevelopmental protein expression and endogenous neurogenesis through inactivation of GSK3β to enhance β-catenin signaling for upexpression of neuroprotective genes and proteins.

  6. Predicting behavioral deficits in pediatric traumatic brain injury through uncinate fasciculus integrity.

    PubMed

    Johnson, Chad P; Juranek, Jenifer; Kramer, Larry A; Prasad, Mary R; Swank, Paul R; Ewing-Cobbs, Linda

    2011-07-01

    Behavioral dysregulation is a common and detrimental consequence of traumatic brain injury (TBI) in children that contributes to poor academic achievement and deficits in social development. Unfortunately, behavioral dysregulation is difficult to predict from either injury severity or early neuropsychological evaluation. The uncinate fasciculus (UF) connects orbitofrontal and anterior temporal lobes, which are commonly implicated in emotional and behavioral regulation. Using probabilistic diffusion tensor tractography (DTT), we examined the relationship between the integrity of the UF 3 months post-injury and ratings of executive functions 12 months post-injury in children with moderate to severe TBI and a comparison group with orthopedic injuries. As expected, fractional anisotropy of the UF was lower in the TBI group relative to the orthopedic injury group. DTT metrics from the UF served as a biomarker and predicted ratings of emotional and behavior regulation, but not metacognition. In contrast, the Glasgow Coma Scale score was not related to either UF integrity or to executive function outcomes. Neuroanatomical biomarkers like the uncinate fasciculus may allow for early identification of behavioral problems and allow for investigation into the relationship of frontotemporal networks to brain-behavior relationships.

  7. Integrating brain, behavior, and phylogeny to understand the evolution of sensory systems in birds

    PubMed Central

    Wylie, Douglas R.; Gutiérrez-Ibáñez, Cristian; Iwaniuk, Andrew N.

    2015-01-01

    The comparative anatomy of sensory systems has played a major role in developing theories and principles central to evolutionary neuroscience. This includes the central tenet of many comparative studies, the principle of proper mass, which states that the size of a neural structure reflects its processing capacity. The size of structures within the sensory system is not, however, the only salient variable in sensory evolution. Further, the evolution of the brain and behavior are intimately tied to phylogenetic history, requiring studies to integrate neuroanatomy with behavior and phylogeny to gain a more holistic view of brain evolution. Birds have proven to be a useful group for these studies because of widespread interest in their phylogenetic relationships and a wealth of information on the functional organization of most of their sensory pathways. In this review, we examine the principle of proper mass in relation differences in the sensory capabilities among birds. We discuss how neuroanatomy, behavior, and phylogeny can be integrated to understand the evolution of sensory systems in birds providing evidence from visual, auditory, and somatosensory systems. We also consider the concept of a “trade-off,” whereby one sensory system (or subpathway within a sensory system), may be expanded in size, at the expense of others, which are reduced in size. PMID:26321905

  8. Performance bounds for dynamic causal modeling of brain connectivity.

    PubMed

    Wu, Shun Chi; Swindlehurst, A Lee

    2012-01-01

    The use of complex dynamical models have been proposed for describing the connections and causal interactions between different regions of the brain. The goal of these models is to accurately mimic the event-related potentials observed by EEG/MEG measurement systems, and are useful in understanding overall brain functionality. In this paper, we focus on a class of nonlinear dynamic causal models (DCM) that are described by a set of connectivity parameters. In practice, the DCM parameters are inferred using data obtained by an EEG or MEG sensor array in response to a certain event or stimulus, and the resulting estimates are used to analyze the strength and direction of the causal interactions between different brain regions. The usefulness of the parameter estimates will depend on how accurately they can be estimated, which in turn will depend on noise, the sampling rate, number of data samples collected, the accuracy of the source localization and reconstruction steps, etc. The goal of this paper is to derive Cramér-Rao performance bounds for DCM estimates, and examine the behavior of the bounds under different operating conditions.

  9. Coastal Ecosystem Integrated Compartment Model (ICM): Modeling Framework

    NASA Astrophysics Data System (ADS)

    Meselhe, E. A.; White, E. D.; Reed, D.

    2015-12-01

    The Integrated Compartment Model (ICM) was developed as part of the 2017 Coastal Master Plan modeling effort. It is a comprehensive and numerical hydrodynamic model coupled to various geophysical process models. Simplifying assumptions related to some of the flow dynamics are applied to increase the computational efficiency of the model. The model can be used to provide insights about coastal ecosystems and evaluate restoration strategies. It builds on existing tools where possible and incorporates newly developed tools where necessary. It can perform decadal simulations (~ 50 years) across the entire Louisiana coast. It includes several improvements over the approach used to support the 2012 Master Plan, such as: additional processes in the hydrology, vegetation, wetland and barrier island morphology subroutines, increased spatial resolution, and integration of previously disparate models into a single modeling framework. The ICM includes habitat suitability indices (HSIs) to predict broad spatial patterns of habitat change, and it provides an additional integration to a dynamic fish and shellfish community model which quantitatively predicts potential changes in important fishery resources. It can be used to estimate the individual and cumulative effects of restoration and protection projects on the landscape, including a general estimate of water levels associated with flooding. The ICM is also used to examine possible impacts of climate change and future environmental scenarios (e.g. precipitation, Eustatic sea level rise, subsidence, tropical storms, etc.) on the landscape and on the effectiveness of restoration projects. The ICM code is publically accessible, and coastal restoration and protection groups interested in planning-level modeling are encouraged to explore its utility as a computationally efficient tool to examine ecosystem response to future physical or ecological changes, including the implementation of restoration and protection strategies.

  10. Industrial ecology in integrated assessment models

    NASA Astrophysics Data System (ADS)

    Pauliuk, Stefan; Arvesen, Anders; Stadler, Konstantin; Hertwich, Edgar G.

    2017-01-01

    Technology-rich integrated assessment models (IAMs) address possible technology mixes and future costs of climate change mitigation by generating scenarios for the future industrial system. Industrial ecology (IE) focuses on the empirical analysis of this system. We conduct an in-depth review of five major IAMs from an IE perspective and reveal differences between the two fields regarding the modelling of linkages in the industrial system, focussing on AIM/CGE, GCAM, IMAGE, MESSAGE, and REMIND. IAMs ignore material cycles and recycling, incoherently describe the life-cycle impacts of technology, and miss linkages regarding buildings and infrastructure. Adding IE system linkages to IAMs adds new constraints and allows for studying new mitigation options, both of which may lead to more robust and policy-relevant mitigation scenarios.

  11. Performance of an integrated network model

    PubMed Central

    Lehmann, François; Dunn, David; Beaulieu, Marie-Dominique; Brophy, James

    2016-01-01

    Objective To evaluate the changes in accessibility, patients’ care experiences, and quality-of-care indicators following a clinic’s transformation into a fully integrated network clinic. Design Mixed-methods study. Setting Verdun, Que. Participants Data on all patient visits were used, in addition to 2 distinct patient cohorts: 134 patients with chronic illness (ie, diabetes, arteriosclerotic heart disease, or both); and 450 women between the ages of 20 and 70 years. Main outcome measures Accessibility was measured by the number of walk-in visits, scheduled visits, and new patient enrolments. With the first cohort, patients’ care experiences were measured using validated serial questionnaires; and quality-of-care indicators were measured using biologic data. With the second cohort, quality of preventive care was measured using the number of Papanicolaou tests performed as a surrogate marker. Results Despite a negligible increase in the number of physicians, there was an increase in accessibility after the clinic’s transition to an integrated network model. During the first 4 years of operation, the number of scheduled visits more than doubled, nonscheduled visits (walk-in visits) increased by 29%, and enrolment of vulnerable patients (those with chronic illnesses) at the clinic remained high. Patient satisfaction with doctors was rated very highly at all points of time that were evaluated. While the number of Pap tests done did not increase with time, the proportion of patients meeting hemoglobin A1c and low-density lipoprotein guideline target levels increased, as did the number of patients tested for microalbuminuria. Conclusion Transformation to an integrated network model of care led to increased efficiency and enhanced accessibility with no negative effects on the doctor-patient relationship. Improvements in biologic data also suggested better quality of care. PMID:27521410

  12. Whole Brain Radiotherapy With Hippocampal Avoidance and Simultaneous Integrated Boost for 1-3 Brain Metastases: A Feasibility Study Using Volumetric Modulated Arc Therapy

    SciTech Connect

    Hsu, Fred; Carolan, Hannah; Nichol, Alan; Cao, Fred; Nuraney, Nimet; Lee, Richard; Gete, Ermias; Wong, Frances; Schmuland, Moira; Heran, Manraj; Otto, Karl

    2010-04-15

    Purpose: To evaluate the feasibility of using volumetric modulated arc therapy (VMAT) to deliver whole brain radiotherapy (WBRT) with hippocampal avoidance and a simultaneous integrated boost (SIB) for one to three brain metastases. Methods and Materials: Ten patients previously treated with stereotactic radiosurgery for one to three brain metastases underwent repeat planning using VMAT. The whole brain prescription dose was 32.25 Gy in 15 fractions, and SIB doses to brain metastases were 63 Gy to lesions >=2.0 cm and 70.8 Gy to lesions <2.0 cm in diameter. The mean dose to the hippocampus was kept at <6 Gy{sub 2}. Plans were optimized for conformity and target coverage while minimizing hippocampal and ocular doses. Plans were evaluated on target coverage, prescription isodose to target volume ratio, conformity number, homogeneity index, and maximum dose to prescription dose ratio. Results: Ten patients had 18 metastases. Mean values for the brain metastases were as follows: conformity number = 0.73 +- 0.10, target coverage = 0.98 +- 0.01, prescription isodose to target volume = 1.34 +- 0.19, maximum dose to prescription dose ratio = 1.09 +- 0.02, and homogeneity index = 0.07 +- 0.02. For the whole brain, the mean target coverage and homogeneity index were 0.960 +- 0.002 and 0.39 +- 0.06, respectively. The mean hippocampal dose was 5.23 +- 0.39 Gy{sub 2}. The mean treatment delivery time was 3.6 min (range, 3.3-4.1 min). Conclusions: VMAT was able to achieve adequate whole brain coverage with conformal hippocampal avoidance and radiosurgical quality dose distributions for one to three brain metastases. The mean delivery time was under 4 min.

  13. Fluid-percussion–induced traumatic brain injury model in rats

    PubMed Central

    Kabadi, Shruti V.; Hilton, Genell D.; Stoica, Bogdan A.; Zapple, David N.; Faden, Alan I.

    2013-01-01

    Traumatic brain injury (TBI) is a major cause of mortality and morbidity. Various attempts have been made to replicate clinical TBI using animal models. The fluid-percussion model (FP) is one of the oldest and most commonly used models of experimentally induced TBI. Both central (CFP) and lateral (LFP) variations of the model have been used. Developed initially for use in larger species, the standard FP device was adapted more than 20 years ago to induce consistent degrees of brain injury in rodents. Recently, we developed a microprocessor-controlled, pneumatically driven instrument, micro-FP (MFP), to address operational concerns associated with the use of the standard FP device in rodents. We have characterized the MFP model with regard to injury severity according to behavioral and histological outcomes. In this protocol, we review the FP models and detail surgical procedures for LFP. The surgery involves tracheal intubation, craniotomy and fixation of Luer fittings, and induction of injury. The surgical procedure can be performed within 45–50 min. PMID:20725070

  14. In vitro bioengineered model of cortical brain tissue

    PubMed Central

    Chwalek, Karolina; Tang-Schomer, Min D.; Omenetto, Fiorenzo G.; Kaplan, David L.

    2016-01-01

    A bioengineered model of three-dimensional (3D) brain-like tissue was developed using silk-collagen protein scaffolds seeded with primary cortical neurons. The scaffold design provides compartmentalized control for spatial separation of neuronal cell bodies and neural projections, resembling the layered structure of the brain (cerebral cortex). Neurons seeded in a donut-shaped porous silk sponge grow robust neuronal projections within a collagen-filled central region, generating 3D neural networks with structural and functional connectivity. The silk scaffold preserves the mechanical stability of the engineered tissues, allowing for ease of handling, long-term culture in vitro, anchoring of the central collagen gel to avoid shrinkage, and neural network maturation. This protocol describes the preparation and manipulation of silk-collagen constructs, including the isolation and seeding of primary rat cortical neurons. This 3D technique is useful for mechanical injury studies, as a drug screening tool and could serve as a foundation for brain-related disease models. The protocol of construct assembly takes 2 days and the resulting tissues can be maintained in culture for several weeks. PMID:26270395

  15. Advances in NLTE Modeling for Integrated Simulations

    SciTech Connect

    Scott, H A; Hansen, S B

    2009-07-08

    The last few years have seen significant progress in constructing the atomic models required for non-local thermodynamic equilibrium (NLTE) simulations. Along with this has come an increased understanding of the requirements for accurately modeling the ionization balance, energy content and radiative properties of different elements for a wide range of densities and temperatures. Much of this progress is the result of a series of workshops dedicated to comparing the results from different codes and computational approaches applied to a series of test problems. The results of these workshops emphasized the importance of atomic model completeness, especially in doubly excited states and autoionization transitions, to calculating ionization balance, and the importance of accurate, detailed atomic data to producing reliable spectra. We describe a simple screened-hydrogenic model that calculates NLTE ionization balance with surprising accuracy, at a low enough computational cost for routine use in radiation-hydrodynamics codes. The model incorporates term splitting, {Delta}n = 0 transitions, and approximate UTA widths for spectral calculations, with results comparable to those of much more detailed codes. Simulations done with this model have been increasingly successful at matching experimental data for laser-driven systems and hohlraums. Accurate and efficient atomic models are just one requirement for integrated NLTE simulations. Coupling the atomic kinetics to hydrodynamics and radiation transport constrains both discretizations and algorithms to retain energy conservation, accuracy and stability. In particular, the strong coupling between radiation and populations can require either very short timesteps or significantly modified radiation transport algorithms to account for NLTE material response. Considerations such as these continue to provide challenges for NLTE simulations.

  16. Building better biomarkers: brain models in translational neuroimaging.

    PubMed

    Woo, Choong-Wan; Chang, Luke J; Lindquist, Martin A; Wager, Tor D

    2017-02-23

    Despite its great promise, neuroimaging has yet to substantially impact clinical practice and public health. However, a developing synergy between emerging analysis techniques and data-sharing initiatives has the potential to transform the role of neuroimaging in clinical applications. We review the state of translational neuroimaging and outline an approach to developing brain signatures that can be shared, tested in multiple contexts and applied in clinical settings. The approach rests on three pillars: (i) the use of multivariate pattern-recognition techniques to develop brain signatures for clinical outcomes and relevant mental processes; (ii) assessment and optimization of their diagnostic value; and (iii) a program of broad exploration followed by increasingly rigorous assessment of generalizability across samples, research contexts and populations. Increasingly sophisticated models based on these principles will help to overcome some of the obstacles on the road from basic neuroscience to better health and will ultimately serve both basic and applied goals.

  17. Reversed item bias: an integrative model.

    PubMed

    Weijters, Bert; Baumgartner, Hans; Schillewaert, Niels

    2013-09-01

    In the recent methodological literature, various models have been proposed to account for the phenomenon that reversed items (defined as items for which respondents' scores have to be recoded in order to make the direction of keying consistent across all items) tend to lead to problematic responses. In this article we propose an integrative conceptualization of three important sources of reversed item method bias (acquiescence, careless responding, and confirmation bias) and specify a multisample confirmatory factor analysis model with 2 method factors to empirically test the hypothesized mechanisms, using explicit measures of acquiescence and carelessness and experimentally manipulated versions of a questionnaire that varies 3 item arrangements and the keying direction of the first item measuring the focal construct. We explain the mechanisms, review prior attempts to model reversed item bias, present our new model, and apply it to responses to a 4-item self-esteem scale (N = 306) and the 6-item Revised Life Orientation Test (N = 595). Based on the literature review and the empirical results, we formulate recommendations on how to use reversed items in questionnaires.

  18. A comparison of hyperelastic constitutive models applicable to brain and fat tissues

    PubMed Central

    Mihai, L. Angela; Chin, LiKang; Janmey, Paul A.; Goriely, Alain

    2015-01-01

    In some soft biological structures such as brain and fat tissues, strong experimental evidence suggests that the shear modulus increases significantly under increasing compressive strain, but not under tensile strain, whereas the apparent Young's elastic modulus increases or remains almost constant when compressive strain increases. These tissues also exhibit a predominantly isotropic, incompressible behaviour. Our aim is to capture these seemingly contradictory mechanical behaviours, both qualitatively and quantitatively, within the framework of finite elasticity, by modelling a soft tissue as a homogeneous, isotropic, incompressible, hyperelastic material and comparing our results with available experimental data. Our analysis reveals that the Fung and Gent models, which are typically used to model soft tissues, are inadequate for the modelling of brain or fat under combined stretch and shear, and so are the classical neo-Hookean and Mooney–Rivlin models used for elastomers. However, a subclass of Ogden hyperelastic models are found to be in excellent agreement with the experiments. Our findings provide explicit models suitable for integration in large-scale finite-element computations. PMID:26354826

  19. A comparison of hyperelastic constitutive models applicable to brain and fat tissues.

    PubMed

    Mihai, L Angela; Chin, LiKang; Janmey, Paul A; Goriely, Alain

    2015-09-06

    In some soft biological structures such as brain and fat tissues, strong experimental evidence suggests that the shear modulus increases significantly under increasing compressive strain, but not under tensile strain, whereas the apparent Young's elastic modulus increases or remains almost constant when compressive strain increases. These tissues also exhibit a predominantly isotropic, incompressible behaviour. Our aim is to capture these seemingly contradictory mechanical behaviours, both qualitatively and quantitatively, within the framework of finite elasticity, by modelling a soft tissue as a homogeneous, isotropic, incompressible, hyperelastic material and comparing our results with available experimental data. Our analysis reveals that the Fung and Gent models, which are typically used to model soft tissues, are inadequate for the modelling of brain or fat under combined stretch and shear, and so are the classical neo-Hookean and Mooney-Rivlin models used for elastomers. However, a subclass of Ogden hyperelastic models are found to be in excellent agreement with the experiments. Our findings provide explicit models suitable for integration in large-scale finite-element computations.

  20. An integrated modeling method for wind turbines

    NASA Astrophysics Data System (ADS)

    Fadaeinedjad, Roohollah

    To study the interaction of the electrical, mechanical, and aerodynamic aspects of a wind turbine, a detailed model that considers all these aspects must be used. A drawback of many studies in the area of wind turbine simulation is that either a very simple mechanical model is used with a detailed electrical model, or vice versa. Hence the interactions between electrical and mechanical aspects of wind turbine operation are not accurately taken into account. In this research, it will be shown that a combination of different simulation packages, namely TurbSim, FAST, and Simulink can be used to model the aerodynamic, mechanical, and electrical aspects of a wind turbine in detail. In this thesis, after a review of some wind turbine concepts and software tools, a simulation structure is proposed for studying wind turbines that integrates the mechanical and electrical components of a wind energy conversion device. Based on the simulation structure, a comprehensive model for a three-bladed variable speed wind turbine with doubly-fed induction generator is developed. Using the model, the impact of a voltage sag on the wind turbine tower vibration is investigated under various operating conditions such as power system short circuit level, mechanical parameters, and wind turbine operating conditions. It is shown how an electrical disturbance can cause more sustainable tower vibrations under high speed and turbulent wind conditions, which may disrupt the operation of pitch control system. A similar simulation structure is used to model a two-bladed fixed speed wind turbine with an induction generator. An extension of the concept is introduced by adding a diesel generator system. The model is utilized to study the impact of the aeroelastic aspects of wind turbine (i.e. tower shadow, wind shears, yaw error, turbulence, and mechanical vibrations) on the power quality of a stand-alone wind-diesel system. Furthermore, an IEEE standard flickermeter model is implemented in a

  1. Integrating Visualizations into Modeling NEST Simulations

    PubMed Central

    Nowke, Christian; Zielasko, Daniel; Weyers, Benjamin; Peyser, Alexander; Hentschel, Bernd; Kuhlen, Torsten W.

    2015-01-01

    Modeling large-scale spiking neural networks showing realistic biological behavior in their dynamics is a complex and tedious task. Since these networks consist of millions of interconnected neurons, their simulation produces an immense amount of data. In recent years it has become possible to simulate even larger networks. However, solutions to assist researchers in understanding the simulation's complex emergent behavior by means of visualization are still lacking. While developing tools to partially fill this gap, we encountered the challenge to integrate these tools easily into the neuroscientists' daily workflow. To understand what makes this so challenging, we looked into the workflows of our collaborators and analyzed how they use the visualizations to solve their daily problems. We identified two major issues: first, the analysis process can rapidly change focus which requires to switch the visualization tool that assists in the current problem domain. Second, because of the heterogeneous data that results from simulations, researchers want to relate data to investigate these effectively. Since a monolithic application model, processing and visualizing all data modalities and reflecting all combinations of possible workflows in a holistic way, is most likely impossible to develop and to maintain, a software architecture that offers specialized visualization tools that run simultaneously and can be linked together to reflect the current workflow, is a more feasible approach. To this end, we have developed a software architecture that allows neuroscientists to integrate visualization tools more closely into the modeling tasks. In addition, it forms the basis for semantic linking of different visualizations to reflect the current workflow. In this paper, we present this architecture and substantiate the usefulness of our approach by common use cases we encountered in our collaborative work. PMID:26733860

  2. Biothermal Model of Patient for Brain Hypothermia Treatment

    NASA Astrophysics Data System (ADS)

    Wakamatsu, Hidetoshi; Gaohua, Lu

    A biothermal model of patient is proposed and verified for the brain hypothermia treatment, since the conventionally applied biothermal models are inappropriate for their unprecedented application. The model is constructed on the basis of the clinical practice of the pertinent therapy and characterized by the mathematical relation with variable ambient temperatures, in consideration of the clinical treatments such as the vital cardiopulmonary regulation. It has geometrically clear representation of multi-segmental core-shell structure, database of physiological and physical parameters with a systemic state equation setting the initial temperature of each compartment. Its step response gives the time constant about 3 hours in agreement with clinical knowledge. As for the essential property of the model, the dynamic temperature of its face-core compartment is realized, which corresponds to the tympanic membrane temperature measured under the practical anesthesia. From the various simulations consistent with the phenomena of clinical practice, it is concluded that the proposed model is appropriate for the theoretical analysis and clinical application to the brain hypothermia treatment.

  3. Age-related cognitive gains are mediated by the effects of white matter development on brain network integration.

    PubMed

    Stevens, Michael C; Skudlarski, Pawel; Pearlson, Godfrey D; Calhoun, Vince D

    2009-12-01

    A fundamental, yet rarely tested premise of developmental cognitive neuroscience is that changes in brain activity and improvements in behavioral control across adolescent development are related to brain maturational factors that shape a more efficient, highly-interconnected brain in adulthood. We present the first multimodal neuroimaging study to empirically demonstrate that maturation of executive cognitive ability is directly associated with the relationship of white matter development and age-related changes in neural network functional integration. In this study, we identified specific white matter regions whose maturation across adolescence appears to reduce reliance on local processing in brain regions recruited for conscious, deliberate cognitive control in favor of a more widely distributed profile of functionally-integrated brain activity. Greater white matter coherence with age was associated with both increases and decreases in functional connectivity within task-engaged functional circuits. Importantly, these associations between white matter development and brain system functional integration were related to behavioral performance on tests of response inhibition, demonstrating their importance in the maturation of optimal cognitive control.

  4. Blast-Associated Shock Waves Result in Increased Brain Vascular Leakage and Elevated ROS Levels in a Rat Model of Traumatic Brain Injury

    PubMed Central

    Petro, Marianne; Dudzinski, Dave; Stewart, Desiree; Courtney, Amy; Courtney, Michael; Labhasetwar, Vinod

    2015-01-01

    Blast-associated shock wave-induced traumatic brain injury (bTBI) remains a persistent risk for armed forces worldwide, yet its detailed pathophysiology remains to be fully investigated. In this study, we have designed and characterized a laboratory-scale shock tube to develop a rodent model of bTBI. Our blast tube, driven by a mixture of oxygen and acetylene, effectively generates blast overpressures of 20–130 psi, with pressure-time profiles similar to those of free-field blast waves. We tested our shock tube for brain injury response to various blast wave conditions in rats. The results show that blast waves cause diffuse vascular brain damage, as determined using a sensitive optical imaging method based on the fluorescence signal of Evans Blue dye extravasation developed in our laboratory. Vascular leakage increased with increasing blast overpressures and mapping of the brain slices for optical signal intensity indicated nonhomogeneous damage to the cerebral vasculature. We confirmed vascular leakage due to disruption in the blood-brain barrier (BBB) integrity following blast exposure. Reactive oxygen species (ROS) levels in the brain also increased with increasing blast pressures and with time post-blast wave exposure. Immunohistochemical analysis of the brain sections analyzed at different time points post blast exposure demonstrated astrocytosis and cell apoptosis, confirming sustained neuronal injury response. The main advantages of our shock-tube design are minimal jet effect and no requirement for specialized equipment or facilities, and effectively generate blast-associated shock waves that are relevant to battle-field conditions. Overall data suggest that increased oxidative stress and BBB disruption could be the crucial factors in the propagation and spread of neuronal degeneration following blast injury. Further studies are required to determine the interplay between increased ROS activity and BBB disruption to develop effective therapeutic

  5. A multifactorial and integrative approach to impulsivity in neuropsychology: insights from the UPPS model of impulsivity.

    PubMed

    Rochat, Lucien; Billieux, Joël; Gagnon, Jean; Van der Linden, Martial

    2017-04-11

    Risky and excessive behaviors, such as aggressive and compulsive behaviors, are frequently described in patients with brain damage and have dramatic psychosocial consequences. Although there is strong evidence that impulsivity constitutes a key factor at play in these behaviors, the literature about impulsivity in neuropsychology is to date scarce. In addition, examining and understanding these problematic behaviors requires the assumption that impulsivity is a multidimensional construct. Consequently, this article aims at shedding light on frequent risky and excessive behaviors in patients with brain damage by focusing on a unified, comprehensive, and well-validated model, namely, the UPPS model of impulsivity. This model considers impulsivity as a multidimensional construct that includes four facets: urgency, (lack of) premeditation, (lack of) perseverance, and sensation seeking. Furthermore, we discuss the psychological mechanisms underlying the dimensions of impulsivity, as well as the laboratory tasks designed to assess each mechanism and their neural bases. We then present a scale specifically designed to assess these four dimensions of impulsivity in patients with brain damage and examine the data regarding this multidimensional approach to impulsivity in neuropsychology. This review supports the need to adopt a multifactorial and integrative approach toward impulsive behaviors, and the model presented provides a valuable rationale to disentangle the nature of brain systems and mechanisms underlying impulsive behaviors in patients with brain damage. It may also foster further relevant research in the field of impulsivity and improve assessment and rehabilitation of impulsive behaviors in clinical settings.

  6. A monolithic integrated low-voltage deep brain stimulator with wireless power and data transmission

    NASA Astrophysics Data System (ADS)

    Zhang, Zhang; Ye, Tan; Jianmin, Zeng; Xu, Han; Xin, Cheng; Guangjun, Xie

    2016-09-01

    A monolithic integrated low-voltage deep brain stimulator with wireless power and data transmission is presented. Data and power are transmitted to the stimulator by mutual inductance coupling, while the in-vitro controller encodes the stimulation parameters. The stimulator integrates the digital control module and can generate the bipolar current with equal amplitude in four channels. In order to reduce power consumption, a novel controlled threshold voltage cancellation rectifier is proposed in this paper to provide the supply voltage of the stimulator. The monolithic stimulator was fabricated in a SMIC 0.18 μm 1-poly 6-metal mixed-signal CMOS process, occupying 0.23 mm2, and consumes 180 μW on average. Compared with previously published stimulators, this design has advantages of large stimulated current (0-0.8 mA) with the double low-voltage supply (1.8 and 3.3 V), and high-level integration. Project supported by the National Natural Science Foundation of China (Nos. 61404043, 61401137), the Key Laboratory of Infrared Imaging Materials and Detectors, Shanghai Institute of Technical Physics, Chinese Academy of Sciences (Nos. IIMDKFJJ-13-06, IIMDKFJJ-14-03), and the Fundamental Research Funds for the Central Universities (No. 2015HGZX0026).

  7. [The Granger causality models and their applications in brain effective connectivity networks].

    PubMed

    Zhao, Tiezhu; Zheng, Gang; Pan, Zhiying; Li, Qiang; Wang, Li; Lu, Guangming

    2013-12-01

    Granger causality model is an analysis method that requires no priori knowledge and emphasizes time sequence. Such model applied to brain effective connectivity network can reflect the directional connectivity among brain regions or neurons. This paper reviews the principle of Granger causality model, basic test steps and improved models, analyzes and discusses applications and existing problems of Granger causality model in brain effective connectivity network.

  8. Organotypic brain slice cultures as a model to study angiogenesis of brain vessels

    PubMed Central

    Hutter-Schmid, Bianca; Kniewallner, Kathrin M.; Humpel, Christian

    2015-01-01

    Brain vessels are the most important structures in the brain to deliver energy and substrates to neurons. Brain vessels are composed of a complex interaction between endothelial cells, pericytes, and astrocytes, controlling the entry of substrates into the brain. Damage of brain vessels and vascular impairment are general pathologies observed in different neurodegenerative disorders including e.g., Alzheimer's disease. In order to study remodeling of brain vessels, simple 3-dimensional in vitro systems need to be developed. Organotypic brain slices of mice provide a potent tool to explore angiogenic effects of brain vessels in a complex 3-dimensional structure. Here we show that organotypic brain slices can be cultured from 110 μm thick sections of postnatal and adult mice brains. The vessels are immunohistochemically stained for laminin and collagen IV. Co-stainings are an appropriate method to visualize interaction of brain endothelial cells with pericytes and astrocytes in these vessels. Different exogenous stimuli such as fibroblast growth factor-2 or vascular endothelial growth factor induce angiogenesis or re-growth, respectively. Hyperthermia or acidosis reduces the vessel density in organotypic slices. In conclusion, organotypic brain slices exhibit a strong vascular network which can be used to study remodeling and angiogenesis of brain vessels in a 3-dimensional in vitro system. PMID:26389117

  9. TU-G-210-01: Modeling for Breast and Brain HIFU Treatment Planning

    SciTech Connect

    Christensen, D.

    2015-06-15

    Modeling can play a vital role in predicting, optimizing and analyzing the results of therapeutic ultrasound treatments. Simulating the propagating acoustic beam in various targeted regions of the body allows for the prediction of the resulting power deposition and temperature profiles. In this session we will apply various modeling approaches to breast, abdominal organ and brain treatments. Of particular interest is the effectiveness of procedures for correcting for phase aberrations caused by intervening irregular tissues, such as the skull in transcranial applications or inhomogeneous breast tissues. Also described are methods to compensate for motion in targeted abdominal organs such as the liver or kidney. Douglas Christensen – Modeling for Breast and Brain HIFU Treatment Planning Tobias Preusser – TRANS-FUSIMO – An Integrative Approach to Model-Based Treatment Planning of Liver FUS Tobias Preusser – TRANS-FUSIMO – An Integrative Approach to Model-Based Treatment Planning of Liver FUS Learning Objectives: Understand the role of acoustic beam modeling for predicting the effectiveness of therapeutic ultrasound treatments. Apply acoustic modeling to specific breast, liver, kidney and transcranial anatomies. Determine how to obtain appropriate acoustic modeling parameters from clinical images. Understand the separate role of absorption and scattering in energy delivery to tissues. See how organ motion can be compensated for in ultrasound therapies. Compare simulated data with clinical temperature measurements in transcranial applications. Supported by NIH R01 HL172787 and R01 EB013433 (DC); EU Seventh Framework Programme (FP7/2007-2013) under 270186 (FUSIMO) and 611889 (TRANS-FUSIMO)(TP); and P01 CA159992, GE, FUSF and InSightec (UV)

  10. Multimodal sensory integration in insects--towards insect brain control architectures.

    PubMed

    Wessnitzer, Jan; Webb, Barbara

    2006-09-01

    Although a variety of basic insect behaviours have inspired successful robot implementations, more complex capabilities in these 'simple' animals are often overlooked. By reviewing the general architecture of their nervous systems, we gain insight into how they are able to integrate behaviours, perform pattern recognition, context-dependent learning, and combine many sensory inputs in tasks such as navigation. We review in particular what is known about two specific 'higher' areas in the insect brain, the mushroom bodies and the central complex, and how they are involved in controlling an insect's behaviour. While much of the functional interpretation of this information is still speculative, it nevertheless suggests some promising new approaches to obtaining adaptive behaviour in robots.

  11. Integrating mind and brain: Warren S. McCulloch, cerebral localization, and experimental epistemology.

    PubMed

    Abraham, Tara H

    2003-03-01

    Recently, historians have focused on Warren S. McCulloch's role in the cybernetics movement during the 1940s and 1950s, and his contributions to the development of computer science and communication theory. What has received less attention is McCulloch's early work in neurophysiology, and its relationship to his philosophical quest for an 'experimental epistemology' - a physiological theory of knowledge. McCulloch's early laboratory work during the 1930s addressed the problem of cerebral localization: localizing aspects of behaviour in the cerebral cortex of the brain. Most of this research was done with the Dutch neurophysiologist J.G. Dusser de Barenne at Yale University. The connection between McCulloch's philosophical interests and his experimental work can be expressed as a search for a physiological a priori, an integrated mechanism of sensation.

  12. A Fuzzy Integral Ensemble Method in Visual P300 Brain-Computer Interface

    PubMed Central

    Cavrini, Francesco; Quitadamo, Lucia Rita; Saggio, Giovanni

    2016-01-01

    We evaluate the possibility of application of combination of classifiers using fuzzy measures and integrals to Brain-Computer Interface (BCI) based on electroencephalography. In particular, we present an ensemble method that can be applied to a variety of systems and evaluate it in the context of a visual P300-based BCI. Offline analysis of data relative to 5 subjects lets us argue that the proposed classification strategy is suitable for BCI. Indeed, the achieved performance is significantly greater than the average of the base classifiers and, broadly speaking, similar to that of the best one. Thus the proposed methodology allows realizing systems that can be used by different subjects without the need for a preliminary configuration phase in which the best classifier for each user has to be identified. Moreover, the ensemble is often capable of detecting uncertain situations and turning them from misclassifications into abstentions, thereby improving the level of safety in BCI for environmental or device control. PMID:26819595

  13. Parkin-independent mitophagy requires Drp1 and maintains the integrity of mammalian heart and brain

    PubMed Central

    Kageyama, Yusuke; Hoshijima, Masahiko; Seo, Kinya; Bedja, Djahida; Sysa-Shah, Polina; Andrabi, Shaida A; Chen, Weiran; Höke, Ahmet; Dawson, Valina L; Dawson, Ted M; Gabrielson, Kathleen; Kass, David A; Iijima, Miho; Sesaki, Hiromi

    2014-01-01

    Mitochondrial dynamics and mitophagy have been linked to cardiovascular and neurodegenerative diseases. Here, we demonstrate that the mitochondrial division dynamin Drp1 and the Parkinson's disease-associated E3 ubiquitin ligase parkin synergistically maintain the integrity of mitochondrial structure and function in mouse heart and brain. Mice lacking cardiac Drp1 exhibited lethal heart defects. In Drp1KO cardiomyocytes, mitochondria increased their connectivity, accumulated ubiquitinated proteins, and decreased their respiration. In contrast to the current views of the role of parkin in ubiquitination of mitochondrial proteins, mitochondrial ubiquitination was independent of parkin in Drp1KO hearts, and simultaneous loss of Drp1 and parkin worsened cardiac defects. Drp1 and parkin also play synergistic roles in neuronal mitochondrial homeostasis and survival. Mitochondrial degradation was further decreased by combination of Drp1 and parkin deficiency, compared with their single loss. Thus, the physiological importance of parkin in mitochondrial homeostasis is revealed in the absence of mitochondrial division in mammals. PMID:25349190

  14. Artificial brains. A million spiking-neuron integrated circuit with a scalable communication network and interface.

    PubMed

    Merolla, Paul A; Arthur, John V; Alvarez-Icaza, Rodrigo; Cassidy, Andrew S; Sawada, Jun; Akopyan, Filipp; Jackson, Bryan L; Imam, Nabil; Guo, Chen; Nakamura, Yutaka; Brezzo, Bernard; Vo, Ivan; Esser, Steven K; Appuswamy, Rathinakumar; Taba, Brian; Amir, Arnon; Flickner, Myron D; Risk, William P; Manohar, Rajit; Modha, Dharmendra S

    2014-08-08

    Inspired by the brain's structure, we have developed an efficient, scalable, and flexible non-von Neumann architecture that leverages contemporary silicon technology. To demonstrate, we built a 5.4-billion-transistor chip with 4096 neurosynaptic cores interconnected via an intrachip network that integrates 1 million programmable spiking neurons and 256 million configurable synapses. Chips can be tiled in two dimensions via an interchip communication interface, seamlessly scaling the architecture to a cortexlike sheet of arbitrary size. The architecture is well suited to many applications that use complex neural networks in real time, for example, multiobject detection and classification. With 400-pixel-by-240-pixel video input at 30 frames per second, the chip consumes 63 milliwatts.

  15. Integration and segregation of large-scale brain networks during short-term task automatization

    PubMed Central

    Mohr, Holger; Wolfensteller, Uta; Betzel, Richard F.; Mišić, Bratislav; Sporns, Olaf; Richiardi, Jonas; Ruge, Hannes

    2016-01-01

    The human brain is organized into large-scale functional networks that can flexibly reconfigure their connectivity patterns, supporting both rapid adaptive control and long-term learning processes. However, it has remained unclear how short-term network dynamics support the rapid transformation of instructions into fluent behaviour. Comparing fMRI data of a learning sample (N=70) with a control sample (N=67), we find that increasingly efficient task processing during short-term practice is associated with a reorganization of large-scale network interactions. Practice-related efficiency gains are facilitated by enhanced coupling between the cingulo-opercular network and the dorsal attention network. Simultaneously, short-term task automatization is accompanied by decreasing activation of the fronto-parietal network, indicating a release of high-level cognitive control, and a segregation of the default mode network from task-related networks. These findings suggest that short-term task automatization is enabled by the brain's ability to rapidly reconfigure its large-scale network organization involving complementary integration and segregation processes. PMID:27808095

  16. Spinal shock and brain death': somatic pathophysiological equivalence and implications for the integrative-unity rationale.

    PubMed

    Shewmon, D A

    1999-05-01

    The somatic pathophysiology of high spinal cord injury (SCI) not only is of interest in itself but also sheds light on one of the several rationales proposed for equating 'brain death' (BD) with death, namely that the brain confers integrative unity upon the body, which would otherwise constitute a mere conglomeration of cells and tissues. Insofar as the neuropathology of BD includes infarction down to the foramen magnum, the somatic pathophysiology of BD should resemble that of cervico-medullary junction transection plus vagotomy. The endocrinologic aspects can be made comparable either by focusing on BD patients without diabetes insipidus or by supposing the victim of high SCI to have pre-existing therapeutically compensated diabetes insipidus. The respective literatures on intensive care for BD organ donors and high SCI corroborate that the two conditions are somatically virtually identical. If SCI victims are alive at the level of the 'organism as a whole', then so must be BD patients (the only significant difference being consciousness). Comparison with SCI leads to the conclusion that if BD is to be equated with death, a more coherent reason must be adduced than that the body as a biological organism is dead.

  17. Sixty minutes of what? A developing brain perspective for activating children with an integrative exercise approach.

    PubMed

    Myer, Gregory D; Faigenbaum, Avery D; Edwards, Nicholas M; Clark, Joseph F; Best, Thomas M; Sallis, Robert E

    2015-12-01

    Current recommendations for physical activity in children overlook the critical importance of motor skill acquisition early in life. Instead, they focus on the quantitative aspects of physical activity (eg, accumulate 60 min of daily moderate to vigorous physical activity) and selected health-related components of physical fitness (eg, aerobic fitness, muscular strength, muscular endurance, flexibility and body composition). This focus on exercise quantity in youth may limit considerations of qualitative aspects of programme design which include (1) skill development, (2) socialisation and (3) enjoyment of exercise. The timing of brain development and associated neuroplasticity for motor skill learning makes the preadolescence period a critical time to develop and reinforce fundamental movement skills in boys and girls. Children who do not participate regularly in structured motor skill-enriched activities during physical education classes or diverse youth sports programmes may never reach their genetic potential for motor skill control which underlies sustainable physical fitness later in life. The goals of this review are twofold: (1) challenge current dogma that is currently focused on the quantitative rather than qualitative aspects of physical activity recommendations for youth and (2) synthesise the latest evidence regarding the brain and motor control that will provide the foundation for integrative exercise programming that provide a framework sustainable activity for life.

  18. Potential implications of Apolipoprotein E in early brain injury after experimental subarachnoid hemorrhage: Involvement in the modulation of blood-brain barrier integrity

    PubMed Central

    Peng, Jianhua; Yang, Ping; Kuai, Li; Qin, Xinghu; Cao, Fang; Sun, Xiaochuan; Chen, Ligang; Vitek, Michael P.; Jiang, Yong

    2016-01-01

    Apolipoprotein E (Apoe) genetic polymorphisms have been implicated in the long term outcome of subarachnoid haemorrhage (SAH), but little is known about the effect of Apoe on the early brain injury (EBI) after SAH. This study investigated the potential role of APOE in EBI post-SAH. Multiple techniques were used to determine the early BBB disruption in EBI post-SAH in a murine model using wild-type (WT) and Apoe−/− (KO) mice. Progressive BBB disruption (Evans blue extravasation and T2 hyperintensity in magnetic resonance imaging) was observed before the peak of endogenous APOE expression elevation at 48h after SAH. Moreover, Apoe−/− mice exhibited more severe BBB disruption charcteristics after SAH than WT mice, including higher levels of Evans blue and IgG extravasation, T2 hyperintensity in magnetic resonance imaging, tight junction proteins degradation and endothelial cells death. Mechanistically, we found that APOE restores the BBB integrity in the acute stage after SAH via the cyclophilin A (CypA)-NF-κB-proinflammatory cytokines-MMP-9 signalling pathway. Consequently, although early BBB disruption causes neurological dysfunctions after SAH, we capture a different aspect of the effects of APOE on EBI after SAH that previous studies had overlooked and open up the idea of BBB disruption as a target of APOE-based therapy for EBI amelioration research in the future. PMID:27463015

  19. Integrative Understanding of Emergent Brain Properties, Quantum Brain Hypotheses, and Connectome Alterations in Dementia are Key Challenges to Conquer Alzheimer's Disease

    PubMed Central

    Kuljiš, Rodrigo O.

    2010-01-01

    The biological substrate for cognition remains a challenge as much as defining this function of living beings. Here, we examine some of the difficulties to understand normal and disordered cognition in humans. We use aspects of Alzheimer's disease and related disorders to illustrate how the wealth of information at many conceptually separate, even intellectually decoupled, physical scales – in particular at the Molecular Neuroscience versus Systems Neuroscience/Neuropsychology levels – presents a challenge in terms of true interdisciplinary integration towards a coherent understanding. These unresolved dilemmas include critically the as yet untested quantum brain hypothesis, and the embryonic attempts to develop and define the so-called connectome in humans and in non-human models of disease. To mitigate these challenges, we propose a scheme incorporating the vast array of scales of the space and time (space–time) manifold from at least the subatomic through cognitive-behavioral dimensions of inquiry, to achieve a new understanding of both normal and disordered cognition, that is essential for a new era of progress in the Generative Sciences and its application to translational efforts for disease prevention and treatment. PMID:21188254

  20. Forward modelling the rubber hand: illusion of ownership modifies motor-sensory predictions by the brain

    PubMed Central

    Petit, Damien; Kheddar, Abderrahmane; Ganesh, Gowrishankar

    2016-01-01

    The question of how we attribute observed body parts as our own, and the consequences of this attribution on our sensory-motor processes, is fundamental to understand how our brain distinguishes between self and other. Previous studies have identified interactions between the illusion of ownership, and multi-sensory integration and cross-sensory predictions by the brain. Here we show that illusory ownership additionally modifies the motor-sensory predictions by the brain. In our preliminary experiments, we observed a new numbness illusion following the classical rubber-hand illusion (RHI); brushing only the rubber hand after induction of the RHI results in illusory numbness in one's real hand. Previous studies have shown that self-generated actions (like tickling) are attenuated by motor-sensory predictions by the so-called forward model. Motivated by this finding, here we examined whether the numbness illusion after the RHI is different when the rubber hand is brushed oneself, compared with when the brushing is performed by another. We observed that, all other conditions remaining the same, haptic perception in the real hand was lower (numbness higher) during self-generated brushing. Our result suggests that RHI reorganizes the forward model, such that we predict haptic consequences of self-generated motor actions on the rubber hand. PMID:27853620

  1. White matter hyperintensities and normal-appearing white matter integrity in the aging brain.

    PubMed

    Maniega, Susana Muñoz; Valdés Hernández, Maria C; Clayden, Jonathan D; Royle, Natalie A; Murray, Catherine; Morris, Zoe; Aribisala, Benjamin S; Gow, Alan J; Starr, John M; Bastin, Mark E; Deary, Ian J; Wardlaw, Joanna M

    2015-02-01

    White matter hyperintensities (WMH) of presumed vascular origin are a common finding in brain magnetic resonance imaging of older individuals and contribute to cognitive and functional decline. It is unknown how WMH form, although white matter degeneration is characterized pathologically by demyelination, axonal loss, and rarefaction, often attributed to ischemia. Changes within normal-appearing white matter (NAWM) in subjects with WMH have also been reported but have not yet been fully characterized. Here, we describe the in vivo imaging signatures of both NAWM and WMH in a large group of community-dwelling older people of similar age using biomarkers derived from magnetic resonance imaging that collectively reflect white matter integrity, myelination, and brain water content. Fractional anisotropy (FA) and magnetization transfer ratio (MTR) were significantly lower, whereas mean diffusivity (MD) and longitudinal relaxation time (T1) were significantly higher, in WMH than NAWM (p < 0.0001), with MD providing the largest difference between NAWM and WMH. Receiver operating characteristic analysis on each biomarker showed that MD differentiated best between NAWM and WMH, identifying 94.6% of the lesions using a threshold of 0.747 × 10(-9) m(2)s(-1) (area under curve, 0.982; 95% CI, 0.975-0.989). Furthermore, the level of deterioration of NAWM was strongly associated with the severity of WMH, with MD and T1 increasing and FA and MTR decreasing in NAWM with increasing WMH score, a relationship that was sustained regardless of distance from the WMH. These multimodal imaging data indicate that WMH have reduced structural integrity compared with surrounding NAWM, and MD provides the best discriminator between the 2 tissue classes even within the mild range of WMH severity, whereas FA, MTR, and T1 only start reflecting significant changes in tissue microstructure as WMH become more severe.

  2. Hindered diffusion of high molecular weight compounds in brain extracellular microenvironment measured with integrative optical imaging.

    PubMed Central

    Nicholson, C; Tao, L

    1993-01-01

    This paper describes the theory of an integrative optical imaging system and its application to the analysis of the diffusion of 3-, 10-, 40-, and 70-kDa fluorescent dextran molecules in agarose gel and brain extracellular microenvironment. The method uses a precisely defined source of fluorescent molecules pressure ejected from a micropipette, and a detailed theory of the intensity contributions from out-of-focus molecules in a three-dimensional medium to a two-dimensional image. Dextrans tagged with either tetramethylrhodamine or Texas Red were ejected into 0.3% agarose gel or rat cortical slices maintained in a perfused chamber at 34 degrees C and imaged using a compound epifluorescent microscope with a 10 x water-immersion objective. About 20 images were taken at 2-10-s intervals, recorded with a cooled CCD camera, then transferred to a 486 PC for quantitative analysis. The diffusion coefficient in agarose gel, D, and the apparent diffusion coefficient, D*, in brain tissue were determined by fitting an integral expression relating the measured two-dimensional image intensity to the theoretical three-dimensional dextran concentration. The measurements in dilute agarose gel provided a reference value of D and validated the method. Values of the tortuosity, lambda = (D/D*)1/2, for the 3- and 10-kDa dextrans were 1.70 and 1.63, respectively, which were consistent with previous values derived from tetramethylammonium measurements in cortex. Tortuosities for the 40- and 70-kDa dextrans had significantly larger values of 2.16 and 2.25, respectively. This suggests that the extracellular space may have local constrictions that hinder the diffusion of molecules above a critical size that lies in the range of many neurotrophic compounds. Images FIGURE 6 FIGURE 8 PMID:7508761

  3. Diffusion tensor imaging reveals adolescent binge ethanol-induced brain structural integrity alterations in adult rats that correlate with behavioral dysfunction.

    PubMed

    Vetreno, Ryan P; Yaxley, Richard; Paniagua, Beatriz; Crews, Fulton T

    2016-07-01

    Adolescence is characterized by considerable brain maturation that coincides with the development of adult behavior. Binge drinking is common during adolescence and can have deleterious effects on brain maturation because of the heightened neuroplasticity of the adolescent brain. Using an animal model of adolescent intermittent ethanol [AIE; 5.0 g/kg, intragastric, 20 percent EtOH w/v; 2 days on/2 days off from postnatal day (P)25 to P55], we assessed the adult brain structural volumes and integrity on P80 and P220 using diffusion tensor imaging (DTI). While we did not observe a long-term effect of AIE on structural volumes, AIE did reduce axial diffusivity (AD) in the cerebellum, hippocampus and neocortex. Radial diffusivity (RD) was reduced in the hippocampus and neocortex of AIE-treated animals. Prior AIE treatment did not affect fractional anisotropy (FA), but did lead to long-term reductions of mean diffusivity (MD) in both the cerebellum and corpus callosum. AIE resulted in increased anxiety-like behavior and diminished object recognition memory, the latter of which was positively correlated with DTI measures. Across aging, whole brain volumes increased, as did volumes of the corpus callosum and neocortex. This was accompanied by age-associated AD reductions in the cerebellum and neocortex as well as RD and MD reductions in the cerebellum. Further, we found that FA increased in both the cerebellum and corpus callosum as rats aged from P80 to P220. Thus, both age and AIE treatment caused long-term changes to brain structural integrity that could contribute to cognitive dysfunction.

  4. A Mixed Approach for Modeling Blood Flow in Brain Microcirculation

    NASA Astrophysics Data System (ADS)

    Peyrounette, M.; Sylvie, L.; Davit, Y.; Quintard, M.

    2014-12-01

    We have previously demonstrated [1] that the vascular system of the healthy human brain cortex is a superposition of two structural components, each corresponding to a different spatial scale. At small-scale, the vascular network has a capillary structure, which is homogeneous and space-filling over a cut-off length. At larger scale, veins and arteries conform to a quasi-fractal branched structure. This structural duality is consistent with the functional duality of the vasculature, i.e. distribution and exchange. From a modeling perspective, this can be viewed as the superposition of: (a) a continuum model describing slow transport in the small-scale capillary network, characterized by a representative elementary volume and effective properties; and (b) a discrete network approach [2] describing fast transport in the arterial and venous network, which cannot be homogenized because of its fractal nature. This problematic is analogous to modeling problems encountered in geological media, e.g, in petroleum engineering, where fast conducting channels (wells or fractures) are embedded in a porous medium (reservoir rock). An efficient method to reduce the computational cost of fractures/continuum simulations is to use relatively large grid blocks for the continuum model. However, this also makes it difficult to accurately couple both structural components. In this work, we solve this issue by adapting the "well model" concept used in petroleum engineering [3] to brain specific 3-D situations. We obtain a unique linear system of equations describing the discrete network, the continuum and the well model coupling. Results are presented for realistic geometries and compared with a non-homogenized small-scale network model of an idealized periodic capillary network of known permeability. [1] Lorthois & Cassot, J. Theor. Biol. 262, 614-633, 2010. [2] Lorthois et al., Neuroimage 54 : 1031-1042, 2011. [3] Peaceman, SPE J. 18, 183-194, 1978.

  5. Perinatal programming of emotional brain circuits: an integrative view from systems to molecules.

    PubMed

    Bock, Jörg; Rether, Kathy; Gröger, Nicole; Xie, Lan; Braun, Katharina

    2014-01-01

    Environmental influences such as perinatal stress have been shown to program the developing organism to adapt brain and behavioral functions to cope with daily life challenges. Evidence is now accumulating that the specific and individual effects of early life adversity on the functional development of brain and behavior emerge as a function of the type, intensity, timing and the duration of the adverse environment, and that early life stress (ELS) is a major risk factor for developing behavioral dysfunctions and mental disorders. Results from clinical as well as experimental studies in animal models support the hypothesis that ELS can induce functional "scars" in prefrontal and limbic brain areas, regions that are essential for emotional control, learning and memory functions. On the other hand, the concept of "stress inoculation" is emerging from more recent research, which revealed positive functional adaptations in response to ELS resulting in resilience against stress and other adversities later in life. Moreover, recent studies indicate that early life experiences and the resulting behavioral consequences can be transmitted to the next generation, leading to a transgenerational cycle of adverse or positive adaptations of brain function and behavior. In this review we propose a unifying view of stress vulnerability and resilience by connecting genetic predisposition and programming sensitivity to the context of experience-expectancy and transgenerational epigenetic traits. The adaptive maturation of stress responsive neural and endocrine systems requires environmental challenges to optimize their functions. Repeated environmental challenges can be viewed within the framework of the match/mismatch hypothesis, the outcome, psychopathology or resilience, depends on the respective predisposition and on the context later in life.

  6. Perinatal programming of emotional brain circuits: an integrative view from systems to molecules

    PubMed Central

    Bock, Jörg; Rether, Kathy; Gröger, Nicole; Xie, Lan; Braun, Katharina

    2014-01-01

    Environmental influences such as perinatal stress have been shown to program the developing organism to adapt brain and behavioral functions to cope with daily life challenges. Evidence is now accumulating that the specific and individual effects of early life adversity on the functional development of brain and behavior emerge as a function of the type, intensity, timing and the duration of the adverse environment, and that early life stress (ELS) is a major risk factor for developing behavioral dysfunctions and mental disorders. Results from clinical as well as experimental studies in animal models support the hypothesis that ELS can induce functional “scars” in prefrontal and limbic brain areas, regions that are essential for emotional control, learning and memory functions. On the other hand, the concept of “stress inoculation” is emerging from more recent research, which revealed positive functional adaptations in response to ELS resulting in resilience against stress and other adversities later in life. Moreover, recent studies indicate that early life experiences and the resulting behavioral consequences can be transmitted to the next generation, leading to a transgenerational cycle of adverse or positive adaptations of brain function and behavior. In this review we propose a unifying view of stress vulnerability and resilience by connecting genetic predisposition and programming sensitivity to the context of experience-expectancy and transgenerational epigenetic traits. The adaptive maturation of stress responsive neural and endocrine systems requires environmental challenges to optimize their functions. Repeated environmental challenges can be viewed within the framework of the match/mismatch hypothesis, the outcome, psychopathology or resilience, depends on the respective predisposition and on the context later in life. PMID:24550772

  7. A Distinct Layer of the Medulla Integrates Sky Compass Signals in the Brain of an Insect

    PubMed Central

    el Jundi, Basil; Pfeiffer, Keram; Homberg, Uwe

    2011-01-01

    Mass migration of desert locusts is a common phenomenon in North Africa and the Middle East but how these insects navigate is still poorly understood. Laboratory studies suggest that locusts are able to exploit the sky polarization pattern as a navigational cue. Like other insects locusts detect polarized light through a specialized dorsal rim area (DRA) of the eye. Polarization signals are transmitted through the optic lobe to the anterior optic tubercle (AOTu) and, finally, to the central complex in the brain. Whereas neurons of the AOTu integrate sky polarization and chromatic cues in a daytime dependent manner, the central complex holds a topographic representation of azimuthal directions suggesting a role as an internal sky compass. To understand further the integration of sky compass cues we studied polarization-sensitive (POL) neurons in the medulla that may be intercalated between DRA photoreceptors and AOTu neurons. Five types of POL-neuron were characterized and four of these in multiple recordings. All neurons had wide arborizations in medulla layer 4 and most, additionally, in the dorsal rim area of the medulla and in the accessory medulla, the presumed circadian clock. The neurons showed type-specific orientational tuning to zenithal polarized light and azimuth tuning to unpolarized green and UV light spots. In contrast to neurons of the AOTu, we found no evidence for color opponency and daytime dependent adjustment of sky compass signals. Therefore, medulla layer 4 is a distinct stage in the integration of sky compass signals that precedes the time-compensated integration of celestial cues in the AOTu. PMID:22114712

  8. A distinct layer of the medulla integrates sky compass signals in the brain of an insect.

    PubMed

    el Jundi, Basil; Pfeiffer, Keram; Homberg, Uwe

    2011-01-01

    Mass migration of desert locusts is a common phenomenon in North Africa and the Middle East but how these insects navigate is still poorly understood. Laboratory studies suggest that locusts are able to exploit the sky polarization pattern as a navigational cue. Like other insects locusts detect polarized light through a specialized dorsal rim area (DRA) of the eye. Polarization signals are transmitted through the optic lobe to the anterior optic tubercle (AOTu) and, finally, to the central complex in the brain. Whereas neurons of the AOTu integrate sky polarization and chromatic cues in a daytime dependent manner, the central complex holds a topographic representation of azimuthal directions suggesting a role as an internal sky compass. To understand further the integration of sky compass cues we studied polarization-sensitive (POL) neurons in the medulla that may be intercalated between DRA photoreceptors and AOTu neurons. Five types of POL-neuron were characterized and four of these in multiple recordings. All neurons had wide arborizations in medulla layer 4 and most, additionally, in the dorsal rim area of the medulla and in the accessory medulla, the presumed circadian clock. The neurons showed type-specific orientational tuning to zenithal polarized light and azimuth tuning to unpolarized green and UV light spots. In contrast to neurons of the AOTu, we found no evidence for color opponency and daytime dependent adjustment of sky compass signals. Therefore, medulla layer 4 is a distinct stage in the integration of sky compass signals that precedes the time-compensated integration of celestial cues in the AOTu.

  9. Hyperbaric oxygen therapy ameliorates local brain metabolism, brain edema and inflammatory response in a blast-induced traumatic brain injury model in rabbits.

    PubMed

    Zhang, Yongming; Yang, Yanyan; Tang, Hong; Sun, Wenjiang; Xiong, Xiaoxing; Smerin, Daniel; Liu, Jiachuan

    2014-05-01

    Many studies suggest that hyperbaric oxygen therapy (HBOT) can provide some clinically curative effects on blast-induced traumatic brain injury (bTBI). The specific mechanism by which this occurs still remains unknown, and no standardized time or course of hyperbaric oxygen treatment is currently used. In this study, bTBI was produced by paper detonators equivalent to 600 mg of TNT exploding at 6.5 cm vertical to the rabbit's head. HBO (100% O2 at 2.0 absolute atmospheres) was used once, 12 h after injury. Magnetic resonance spectroscopy was performed to investigate the impact of HBOT on the metabolism of local injured nerves in brain tissue. We also examined blood-brain barrier (BBB) integrity, brain water content, apoptotic factors, and some inflammatory mediators. Our results demonstrate that hyperbaric oxygen could confer neuroprotection and improve prognosis after explosive injury by promoting the metabolism of local neurons, inhibiting brain edema, protecting BBB integrity, decreasing cell apoptosis, and inhibiting the inflammatory response. Furthermore, timely intervention within 1 week after injury might be more conducive to improving the prognosis of patients with bTBI.

  10. Approximately Integrable Linear Statistical Models in Non-Parametric Estimation

    DTIC Science & Technology

    1990-08-01

    OTIC I EL COPY Lfl 0n Cf) NAPPROXIMATELY INTEGRABLE LINEAR STATISTICAL MODELS IN NON- PARAMETRIC ESTIMATION by B. Ya. Levit University of Maryland...Integrable Linear Statistical Models in Non- Parametric Estimation B. Ya. Levit Sumnmary / The notion of approximately integrable linear statistical models...models related to the study of the "next" order optimality in non- parametric estimation . It appears consistent to keep the exposition at present at the

  11. Experimental models of perinatal hypoxic-ischemic brain damage.

    PubMed

    Vannucci, R C

    1993-01-01

    Animal research has provided important information on the pathogenesis of and neuropathologic responses to perinatal cerebral hypoxia-ischemia. In experimental animals, structural brain damage from hypoxia-ischemia has been produced in immature rats, rabbits, guinea pigs, sheep and monkeys (18, 20, 24, 25, 38). Of the several available animal models, the fetal and newborn rhesus monkey and immature rat have been studied most extensively because of their similarities to humans in respect to the physiology of reproduction and their neuroanatomy at or shortly following birth. Given the frequency of occurrence of human perinatal hypoxic-ischemic brain damage and the multiple, often severe neurologic handicaps which ensue in infants and children, it is not surprising that the above described animal models have been developed. These models have provided the basis for investigations to clarify not only physiologic and biochemical mechanisms of tissue injury but also the efficacy of specific management strategies. Hopefully, such animal research will continue to provide important information regarding how best to prevent or minimize the devastating consequences of perinatal cerebral hypoxia-ischemia.

  12. Melanoma Cells Homing to the Brain: An In Vitro Model

    PubMed Central

    Rizzo, A.; Vasco, C.; Girgenti, V.; Fugnanesi, V.; Calatozzolo, C.; Canazza, A.; Salmaggi, A.; Rivoltini, L.; Morbin, M.; Ciusani, E.

    2015-01-01

    We developed an in vitro contact through-feet blood brain barrier (BBB) model built using type IV collagen, rat astrocytes, and human umbilical vein endothelial cells (HUVECs) cocultured through Transwell porous polycarbonate membrane. The contact between astrocytes and HUVECs was demonstrated by electron microscopy: astrocytes endfeet pass through the 8.0 μm pores inducing HUVECs to assume a cerebral phenotype. Using this model we evaluated transmigration of melanoma cells from two different patients (M1 and M2) selected among seven melanoma primary cultures. M2 cells showed a statistically significant higher capability to pass across the in vitro BBB model, compared to M1. Expression of adhesion molecules was evaluated by flow cytometry: a statistically significant increased expression of MCAM, αvβ3, and CD49b was detected in M1. PCR array data showed that M2 had a higher expression of several matrix metalloproteinase proteins (MMPs) compared to M1. Specifically, data suggest that MMP2 and MMP9 could be directly involved in BBB permeability and that brain invasion by melanoma cells could be related to the overexpression of many MMPs. Future studies will be necessary to deepen the mechanisms of central nervous system invasion. PMID:25692137

  13. Alternative field representations and integral equations for modeling inhomogeneous dielectrics

    NASA Technical Reports Server (NTRS)

    Volakis, John L.

    1992-01-01

    New volume and volume-surface integral equations are presented for modeling inhomogeneous dielectric regions. The presented integral equations result in more efficient numerical implementations and should, therefore, be useful in a variety of electromagnetic applications.

  14. Integrated Meteorology and Chemistry Modeling: Evaluation and Research Needs

    EPA Science Inventory

    Over the past decade several online integrated atmospheric chemical-transport and meteorology modeling systems with varying levels of interactions among different atmospheric processes have been developed. A variety of approaches to meteorology-chemistry integration with differe...

  15. Selectionist models of perceptual and motor systems and implications for functionalist theories of brain function

    NASA Astrophysics Data System (ADS)

    Reeke, George N.; Sporns, Olaf

    1990-06-01

    Functionalism is at present widely accepted as a working basis for cognitive science and artificial intelligence. This view holds that psychological phenomena can be adequately described in terms of functional processes carried out in the brain, and that these processes can be understood independently of the detailed structure and mode of development of the brain. In the functionalist view, the brain is analogous to a computer; both can properly be described at the level of symbolic representations and algorithms. However, an analysis of the structure, development, and evolution of the brain makes it highly unlikely that it could be a Turing machine or that brain algorithms could be either acquired by experience in the world or transmitted between generations. An alternative view is that the brain is a selective system in which two different domains of stochastic variation, the world and neural repertoires, become mapped onto each other in an individual, historical manner. Neural systems capable of such mapping can generalize and can deal with novelty in an open-ended environment. Several models have been constructed to test these ideas, including automata of a new kind that can recognize and associate patterns of sensory input by selective mechanisms. In an approach called synthetic neural modelling, the environment, the phenotype, and the nervous system of such an automaton are integrated into a single computer model. One example is Darwin III, a sessile “creature” with an eye and a multi-jointed arm having a sense of touch; its environment consists of simple shapes moving on a featureless background; its nervous system consists of some 50 000 cells of 50 different kinds connected by about 620 000 synaptic junctions. Darwin III can be trained to track moving objects with its eye, to reach out and touch objects with its arm, to categorize objects according to combinations of visual and tactile cues, and to respond in a positive or negative way to such objects

  16. Integrated Environmental Modelling: human decisions, human challenges

    USGS Publications Warehouse

    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.

  17. Integrated model of the Carlina Telescope

    NASA Astrophysics Data System (ADS)

    Enmark, Anita; Andersen, Torben; Owner-Petersen, Mette; Chakraborty, Rijuparna; Labeyrie, Antoine

    2011-09-01

    The Carlina hypertelescope is a planned sparse aperture 100 m telescope with pupil densification. The telescope has a spherical primary with segments located in a valley between mountains, and additional optical elements in a gondola suspended in eight cables some 100 m above the primary mirror. The resolution is about 1.2×10-3 arcsec. It is imperative that the position and attitude of the gondola be maintained within tight tolerances during observation and star tracking. The present design has servo-controlled winches on the ground for control of the gondola via the cables. An integrated model of the system, including optics, cables, gondola, position and attitude control system, and wind disturbances has been set up. The structural and control models are linear. Calculations in the frequency domain and simulations in the time domain show that the performance of the telescope with the present design seems adequate for short exposures. However, for long-exposure operation, the gondola stability should be improved by about two orders of magnitude. Recommendations are given on possible approaches for performance improvement.

  18. MicroCT and microMRI imaging of a prenatal mouse model of increased brain size

    NASA Astrophysics Data System (ADS)

    López, Elisabeth K. N.; Stock, Stuart R.; Taketo, Makoto M.; Chenn, Anjen; Ravosa, Matthew J.

    2008-08-01

    There are surprisingly few experimental models of neural growth and cranial integration. This and the dearth of information regarding fetal brain development detract from a mechanistic understanding of cranial integration and its relevance to the patterning of skull form, specifically the role of encephalization on basicranial flexion. To address this shortcoming, our research uses transgenic mice expressing a stabilized form of β-catenin to isolate the effects of relative brain size on craniofacial development. These mice develop highly enlarged brains due to an increase in neural precursors, and differences between transgenic and wild-type mice are predicted to result solely from variation in brain size. Comparisons of wild-type and transgenic mice at several prenatal ages were performed using microCT (Scanco Medical MicroCT 40) and microMRI (Avance 600 WB MR spectrometer). Statistical analyses show that the larger brain of the transgenic mice is associated with a larger neurocranium and an altered basicranial morphology. However, body size and postcranial ossification do not seem to be affected by the transgene. Comparisons of the rate of postcranial and cranial ossification using microCT also point to an unexpected effect of neural growth on skull development: increased fetal encephalization may result in a compensatory decrease in the level of cranial ossification. Therefore, if other life history factors are held constant, the ontogeny of a metabolically costly structure such as a brain may occur at the expense of other cranial structures. These analyses indicate the benefits of a multifactorial approach to cranial integration using a mouse model.

  19. Design of a component-based integrated environmental modeling framework

    EPA Science Inventory

    Integrated environmental modeling (IEM) includes interdependent science-based components (e.g., models, databases, viewers, assessment protocols) that comprise an appropriate software modeling system. The science-based components are responsible for consuming and producing inform...

  20. Integrated Medical Model Verification, Validation, and Credibility

    NASA Technical Reports Server (NTRS)

    Walton, Marlei; Kerstman, Eric; Foy, Millennia; Shah, Ronak; Saile, Lynn; Boley, Lynn; Butler, Doug; Myers, Jerry

    2014-01-01

    The Integrated Medical Model (IMM) was designed to forecast relative changes for a specified set of crew health and mission success risk metrics by using a probabilistic (stochastic process) model based on historical data, cohort data, and subject matter expert opinion. A probabilistic approach is taken since exact (deterministic) results would not appropriately reflect the uncertainty in the IMM inputs. Once the IMM was conceptualized, a plan was needed to rigorously assess input information, framework and code, and output results of the IMM, and ensure that end user requests and requirements were considered during all stages of model development and implementation. METHODS: In 2008, the IMM team developed a comprehensive verification and validation (VV) plan, which specified internal and external review criteria encompassing 1) verification of data and IMM structure to ensure proper implementation of the IMM, 2) several validation techniques to confirm that the simulation capability of the IMM appropriately represents occurrences and consequences of medical conditions during space missions, and 3) credibility processes to develop user confidence in the information derived from the IMM. When the NASA-STD-7009 (7009) was published, the IMM team updated their verification, validation, and credibility (VVC) project plan to meet 7009 requirements and include 7009 tools in reporting VVC status of the IMM. RESULTS: IMM VVC updates are compiled recurrently and include 7009 Compliance and Credibility matrices, IMM VV Plan status, and a synopsis of any changes or updates to the IMM during the reporting period. Reporting tools have evolved over the lifetime of the IMM project to better communicate VVC status. This has included refining original 7009 methodology with augmentation from the NASA-STD-7009 Guidance Document. End user requests and requirements are being satisfied as evidenced by ISS Program acceptance of IMM risk forecasts, transition to an operational model and

  1. Integrated Space Asset Management Database and Modeling

    NASA Technical Reports Server (NTRS)

    MacLeod, Todd; Gagliano, Larry; Percy, Thomas; Mason, Shane

    2015-01-01

    Effective Space Asset Management is one key to addressing the ever-growing issue of space congestion. It is imperative that agencies around the world have access to data regarding the numerous active assets and pieces of space junk currently tracked in orbit around the Earth. At the center of this issues is the effective management of data of many types related to orbiting objects. As the population of tracked objects grows, so too should the data management structure used to catalog technical specifications, orbital information, and metadata related to those populations. Marshall Space Flight Center's Space Asset Management Database (SAM-D) was implemented in order to effectively catalog a broad set of data related to known objects in space by ingesting information from a variety of database and processing that data into useful technical information. Using the universal NORAD number as a unique identifier, the SAM-D processes two-line element data into orbital characteristics and cross-references this technical data with metadata related to functional status, country of ownership, and application category. The SAM-D began as an Excel spreadsheet and was later upgraded to an Access database. While SAM-D performs its task very well, it is limited by its current platform and is not available outside of the local user base. Further, while modeling and simulation can be powerful tools to exploit the information contained in SAM-D, the current system does not allow proper integration options for combining the data with both legacy and new M&S tools. This paper provides a summary of SAM-D development efforts to date and outlines a proposed data management infrastructure that extends SAM-D to support the larger data sets to be generated. A service-oriented architecture model using an information sharing platform named SIMON will allow it to easily expand to incorporate new capabilities, including advanced analytics, M&S tools, fusion techniques and user interface for

  2. A mouse model of human repetitive mild traumatic brain injury

    PubMed Central

    Kane, Michael J.; Pérez, Mariana Angoa; Briggs, Denise I.; Viano, David C.; Kreipke, Christian W.; Kuhn, Donald M.

    2011-01-01

    A novel method for the study of repetitive mild traumatic brain injury (rmTBI) that models the most common form of head injury in humans is presented. Existing animal models of TBI impart focal, severe damage unlike that seen in repeated and mild concussive injuries, and few are configured for repetitive application. Our model is a modification of the Marmarou weight drop method and allows repeated head impacts to lightly anesthetized mice. A key facet of this method is the delivery of an impact to the cranium of an unrestrained subject allowing rapid acceleration of the free-moving head and torso, an essential characteristic known to be important for concussive injury in humans, and a factor that is missing from existing animal models of TBI. Our method does not require scalp incision, emplacement of protective skull helmets or surgery and the procedure can be completed in 1-2 minutes. Mice spontaneously recover the righting reflex and show no evidence of seizures, paralysis or impaired behavior. Skull fractures and intracranial bleeding are very rare. Minor deficits in motor coordination and locomotor hyperactivity recover over time. Histological analyses reveal mild astrocytic reactivity (increased expression of GFAP) and increased phospho-tau but a lack of blood-brain-barrier disruption, edema and microglial activation. This new animal model is simple and cost-effective and will facilitate characterization of the neurobiological and behavioral consequences of rmTBI. It is also ideal for high throughput screening of potential new therapies for mild concussive injuries as experienced by athletes and military personnel. PMID:21930157

  3. A mouse model of human repetitive mild traumatic brain injury.

    PubMed

    Kane, Michael J; Angoa-Pérez, Mariana; Briggs, Denise I; Viano, David C; Kreipke, Christian W; Kuhn, Donald M

    2012-01-15

    A novel method for the study of repetitive mild traumatic brain injury (rmTBI) that models the most common form of head injury in humans is presented. Existing animal models of TBI impart focal, severe damage unlike that seen in repeated and mild concussive injuries, and few are configured for repetitive application. Our model is a modification of the Marmarou weight drop method and allows repeated head impacts to lightly anesthetized mice. A key facet of this method is the delivery of an impact to the cranium of an unrestrained subject allowing rapid acceleration of the free-moving head and torso, an essential characteristic known to be important for concussive injury in humans, and a factor that is missing from existing animal models of TBI. Our method does not require scalp incision, emplacement of protective skull helmets or surgery and the procedure can be completed in 1-2 min. Mice spontaneously recover the righting reflex and show no evidence of seizures, paralysis or impaired behavior. Skull fractures and intracranial bleeding are very rare. Minor deficits in motor coordination and locomotor hyperactivity recover over time. Histological analyses reveal mild astrocytic reactivity (increased expression of GFAP) and increased phospho-tau but a lack of blood-brain-barrier disruption, edema and microglial activation. This new animal model is simple and cost-effective and will facilitate characterization of the neurobiological and behavioral consequences of rmTBI. It is also ideal for high throughput screening of potential new therapies for mild concussive injuries as experienced by athletes and military personnel.

  4. Integrated exposure modeling: a model using GIS and GLM.

    PubMed

    Holford, Theodore R; Ebisu, Keita; McKay, Lisa A; Gent, Janneane F; Triche, Elizabeth W; Bracken, Michael B; Leaderer, Brian P

    2010-01-15

    Traffic exhaust is a source of air contaminants that have adverse health effects. Quantification of traffic as an exposure variable is complicated by aerosol dispersion related to variation in layout of roads, traffic density, meteorology, and topography. A statistical model is presented that uses Geographic Information Systems (GIS) technology to incorporate variables into a generalized linear model that estimates distribution of traffic-related pollution. Exposure from a source is expressed as an integral of a function proportional to average daily traffic and a nonparametric dispersion function, which takes the form of a step, polynomial, or spline model. The method may be applied using standard regression techniques for fitting generalized linear models. Modifiers of pollutant dispersion such as wind direction, meteorology, and landscape features can also be included. Two examples are given to illustrate the method. The first employs data from a study in which NO(2) (a known pollutant from automobile exhaust) was monitored outside of 138 Connecticut homes, providing a model for estimating NO(2) exposure. In the second example, estimated levels of nitrogen dioxide (NO(2)) from the model, as well as a separate spatial model, were used to analyze traffic-related health effects in a study of 761 infants.

  5. Fast correspondences for statistical shape models of brain structures

    NASA Astrophysics Data System (ADS)

    Bernard, Florian; Vlassis, Nikos; Gemmar, Peter; Husch, Andreas; Thunberg, Johan; Goncalves, Jorge; Hertel, Frank

    2016-03-01

    Statistical shape models based on point distribution models are powerful tools for image segmentation or shape analysis. The most challenging part in the generation of point distribution models is the identification of corresponding landmarks among all training shapes. Since in general the true correspondences are unknown, correspondences are frequently established under the hypothesis that correct correspondences lead to a compact model, which is mostly tackled by continuous optimisation methods. In favour of the prospect of an efficient optimisation, we present a simplified view of the correspondence problem for statistical shape models that is based on point-set registration, the linear assignment problem and mesh fairing. At first, regularised deformable point-set registration is performed and combined with solving the linear assignment problem to obtain correspondences between shapes on a global scale. With that, rough correspondences are established that may not yet be accurate on a local scale. Then, by using a mesh fairing procedure, consensus of the correspondences on a global and local scale among the entire set of shapes is achieved. We demonstrate that for the generation of statistical shape models of deep brain structures, the proposed approach is preferable over existing population-based methods both in terms of a significantly shorter runtime and in terms of an improved quality of the resulting shape model.

  6. Integrated But Not Whole? Applying an Ontological Account of Human Organismal Unity to the Brain Death Debate.

    PubMed

    Moschella, Melissa

    2016-10-01

    As is clear in the 2008 report of the President's Council on Bioethics, the brain death debate is plagued by ambiguity in the use of such key terms as 'integration' and 'wholeness'. Addressing this problem, I offer a plausible ontological account of organismal unity drawing on the work of Hoffman and Rosenkrantz, and then apply that account to the case of brain death, concluding that a brain dead body lacks the unity proper to a human organism, and has therefore undergone a substantial change. I also show how my view can explain hard cases better than one in which biological integration (as understood by Alan Shewmon and the President's Council) is taken to imply ontological wholeness or unity.

  7. Predicting individual brain functional connectivity using a Bayesian hierarchical model.

    PubMed

    Dai, Tian; Guo, Ying

    2017-02-15

    Network-oriented analysis of functional magnetic resonance imaging (fMRI), especially resting-state fMRI, has revealed important association between abnormal connectivity and brain disorders such as schizophrenia, major depression and Alzheimer's disease. Imaging-based brain connectivity measures have become a useful tool for investigating the pathophysiology, progression and treatment response of psychiatric disorders and neurodegenerative diseases. Recent studies have started to explore the possibility of using functional neuroimaging to help predict disease progression and guide treatment selection for individual patients. These studies provide the impetus to develop statistical methodology that would help provide predictive information on disease progression-related or treatment-related changes in neural connectivity. To this end, we propose a prediction method based on Bayesian hierarchical model that uses individual's baseline fMRI scans, coupled with relevant subject characteristics, to predict the individual's future functional connectivity. A key advantage of the proposed method is that it can improve the accuracy of individualized prediction of connectivity by combining information from both group-level connectivity patterns that are common to subjects with similar characteristics as well as individual-level connectivity features that are particular to the specific subject. Furthermore, our method also offers statistical inference tools such as predictive intervals that help quantify the uncertainty or variability of the predicted outcomes. The proposed prediction method could be a useful approach to predict the changes in individual patient's brain connectivity with the progression of a disease. It can also be used to predict a patient's post-treatment brain connectivity after a specified treatment regimen. Another utility of the proposed method is that it can be applied to test-retest imaging data to develop a more reliable estimator for individual

  8. Probing the extracellular diffusion of antibodies in brain using in vivo integrative optical imaging and ex vivo fluorescence imaging.

    PubMed

    Wolak, Daniel J; Pizzo, Michelle E; Thorne, Robert G

    2015-01-10

    Antibody-based therapeutics exhibit great promise in the treatment of central nervous system (CNS) disorders given their unique customizable properties. Although several clinical trials have evaluated therapeutic antibodies for treatment of CNS disorders, success to date has likely been limited in part due to complex issues associated with antibody delivery to the brain and antibody distribution within the CNS compartment. Major obstacles to effective CNS delivery of full length immunoglobulin G (IgG) antibodies include transport across the blood-brain and blood-cerebrospinal fluid barriers. IgG diffusion within brain extracellular space (ECS) may also play a role in limiting central antibody distribution; however, IgG transport in brain ECS has not yet been explored using established in vivo methods. Here, we used real-time integrative optical imaging to measure the diffusion properties of fluorescently labeled, non-targeted IgG after pressure injection in both free solution and in adult rat neocortex in vivo, revealing IgG diffusion in free medium is ~10-fold greater than in brain ECS. The pronounced hindered diffusion of IgG in brain ECS is likely due to a number of general factors associated with the brain microenvironment (e.g. ECS volume fraction and geometry/width) but also molecule-specific factors such as IgG size, shape, charge and specific binding interactions with ECS components. Co-injection of labeled IgG with an excess of unlabeled Fc fragment yielded a small yet significant increase in the IgG effective diffusion coefficient in brain, suggesting that binding between the IgG Fc domain and endogenous Fc-specific receptors may contribute to the hindered mobility of IgG in brain ECS. Importantly, local IgG diffusion coefficients from integrative optical imaging were similar to those obtained from ex vivo fluorescence imaging of transport gradients across the pial brain surface following controlled intracisternal infusions in anesthetized animals. Taken

  9. Planarian brain regeneration as a model system for developmental neurotoxicology

    PubMed Central

    Hagstrom, Danielle; Cochet‐Escartin, Olivier

    2016-01-01

    Abstract Freshwater planarians, famous for their regenerative prowess, have long been recognized as a valuable in vivo animal model to study the effects of chemical exposure. In this review, we summarize the current techniques and tools used in the literature to assess toxicity in the planarian system. We focus on the planarian's particular amenability for neurotoxicology and neuroregeneration studies, owing to the planarian's unique ability to regenerate a centralized nervous system. Zooming in from the organismal to the molecular level, we show that planarians offer a repertoire of morphological and behavioral readouts while also being amenable to mechanistic studies of compound toxicity. Finally, we discuss the open challenges and opportunities for planarian brain regeneration to become an important model system for modern toxicology. PMID:27499880

  10. Computational modeling of brain pathologies: the case of multiple sclerosis.

    PubMed

    Pappalardo, Francesco; Rajput, Abdul-Mateen; Motta, Santo

    2016-12-22

    The central nervous system is the most complex network of the human body. The existence and functionality of a large number of molecular species in human brain are still ambiguous and mostly unknown, thus posing a challenge to Science and Medicine. Neurological diseases inherit the same level of complexity, making effective treatments difficult to be found. Multiple sclerosis (MS) is a major neurological disease that causes severe inabilities and also a significant social burden on health care system: between 2 and 2.5 million people are affected by it, and the cost associated with it is significantly higher as compared with other neurological diseases because of the chronic nature of the disease and to the partial efficacy of current therapies. Despite difficulties in understanding and treating MS, many computational models have been developed to help neurologists. In the present work, we briefly review the main characteristics of MS and present a selection criteria of modeling approaches.

  11. Empirical models of height integrated conductivities

    NASA Astrophysics Data System (ADS)

    Wallis, D. D.; Budzinski, E. E.

    1981-01-01

    Two-dimensional distributions of the height-integrated Pedersen and Hall conductivities have been computed for latitudes poleward of 60 deg invariant representative of two Kp activity levels. Average precipitating fluxes of electrons with energies of 0.15, 1.27, 9.65, and greater than 22 keV obtained by the energetic particle detector of Isis 2 during 1971-1974 are used as input to a Rees-type computation. The assumption of equilibrium conditions and a recombination rate profile permit calculation of electron density profiles and conductivity profiles. Calculations are performed at 300 grid points, specifically 12 local times and 25 latitudes from 60 to 84 deg invariant latitude. The models include ionization due to galactic EUV and other background sources that produces base conductivities as well as solar photon ionization through an empirical fit to Chatanika radar observations. Substantial modulation of the conductivities is found to result from longitudinal variation of the magnitude of the earth's magnetic field.

  12. STRAW - An Integrated Mobility and Traffic Model for VANETs

    DTIC Science & Technology

    2005-06-01

    STRAW - An Integrated Mobility and Traffic Model for VANETs David R. Choffnes Fabiàn E. Bustamante drchoffnes...3. DATES COVERED 00-00-2005 to 00-00-2005 4. TITLE AND SUBTITLE STRAW - An Integrated Mobility and Traffic Model for VANETs 5a. CONTRACT...STRAW - An Integrated Mobility and Traffic Model for VANETs David R. Choffnes Fabián E. Bustamante Department of Computer Science Northwestern

  13. The Bee as a Model to Investigate Brain and Behavioural Asymmetries

    PubMed Central

    Frasnelli, Elisa; Haase, Albrecht; Rigosi, Elisa; Anfora, Gianfranco; Rogers, Lesley J.; Vallortigara, Giorgio

    2014-01-01

    The honeybee Apis mellifera, with a brain of only 960,000 neurons and the ability to perform sophisticated cognitive tasks, has become an excellent model in life sciences and in particular in cognitive neurosciences. It has been used in our laboratories to investigate brain and behavioural asymmetries, i.e., the different functional specializations of the right and the left sides of the brain. It is well known that bees can learn to associate an odour stimulus with a sugar reward, as demonstrated by extension of the proboscis when presented with the trained odour in the so-called Proboscis Extension Reflex (PER) paradigm. Bees recall this association better when trained using their right antenna than they do when using their left antenna. They also retrieve short-term memory of this task better when using the right antenna. On the other hand, when tested for long-term memory recall, bees respond better when using their left antenna. Here we review a series of behavioural studies investigating bees’ lateralization, integrated with electrophysiological measurements to study asymmetries of olfactory sensitivity, and discuss the possible evolutionary origins of these asymmetries. We also present morphological data obtained by scanning electron microscopy and two-photon microscopy. Finally, a behavioural study conducted in a social context is summarised, showing that honeybees control context-appropriate social interactions using their right antenna, rather than the left, thus suggesting that lateral biases in behaviour might be associated with requirements of social life. PMID:26462583

  14. Radiolysis Model Formulation for Integration with the Mixed Potential Model

    SciTech Connect

    Buck, Edgar C.; Wittman, Richard S.

    2014-07-10

    The U.S. Department of Energy Office of Nuclear Energy (DOE-NE), Office of Fuel Cycle Technology has established the Used Fuel Disposition Campaign (UFDC) to conduct the research and development activities related to storage, transportation, and disposal of used nuclear fuel (UNF) and high-level radioactive waste. Within the UFDC, the components for a general system model of the degradation and subsequent transport of UNF is being developed to analyze the performance of disposal options [Sassani et al., 2012]. Two model components of the near-field part of the problem are the ANL Mixed Potential Model and the PNNL Radiolysis Model. This report is in response to the desire to integrate the two models as outlined in [Buck, E.C, J.L. Jerden, W.L. Ebert, R.S. Wittman, (2013) “Coupling the Mixed Potential and Radiolysis Models for Used Fuel Degradation,” FCRD-UFD-2013-000290, M3FT-PN0806058

  15. Language Model Applications to Spelling with Brain-Computer Interfaces

    PubMed Central

    Mora-Cortes, Anderson; Manyakov, Nikolay V.; Chumerin, Nikolay; Van Hulle, Marc M.

    2014-01-01

    Within the Ambient Assisted Living (AAL) community, Brain-Computer Interfaces (BCIs) have raised great hopes as they provide alternative communication means for persons with disabilities bypassing the need for speech and other motor activities. Although significant advancements have been realized in the last decade, applications of language models (e.g., word prediction, completion) have only recently started to appear in BCI systems. The main goal of this article is to review the language model applications that supplement non-invasive BCI-based communication systems by discussing their potential and limitations, and to discern future trends. First, a brief overview of the most prominent BCI spelling systems is given, followed by an in-depth discussion of the language models applied to them. These language models are classified according to their functionality in the context of BCI-based spelling: the static/dynamic nature of the user interface, the use of error correction and predictive spelling, and the potential to improve their classification performance by using language models. To conclude, the review offers an overview of the advantages and challenges when implementing language models in BCI-based communication systems when implemented in conjunction with other AAL technologies. PMID:24675760

  16. Integrated Belowground Greenhouse Gas Flux Modeling (Invited)

    NASA Astrophysics Data System (ADS)

    Davidson, E. A.; Savage, K. E.

    2013-12-01

    Soil greenhouse gas (GHG) emissions play a significant role as biotic feedbacks to climate change. However, these complex processes, involving C, N, and O2 substrates and inhibitors, interactions with plant processes, and environmental influences of temperature, moisture, and gas transport, remain challenging to simulate in process models. Because CO2, CH4, and N2O production and consumption processes are inter-linked through common substrates and the contrasting effects of O2 as either an essential substrate or a potential inhibitor, the simulation of fluxes of any one gas must be consistent with mechanistic simulations and observations of fluxes of the other gases. Simulating the fluxes of one gas alone is a simpler task, but simulating all three gases simultaneously would provide multiple constraints and would afford greater confidence that the most important mechanisms are aptly simulated. A case in point is the challenge of resolving the apparent paradox of observed simultaneous CO2 production by aerobic respiration, CH4 uptake (oxidation), CH4 production, and N2O uptake (reduction) in the same soil profile. Consumption of atmospheric N2O should occur only under reducing conditions, and yet we have observed uptake of atmospheric CH4 (oxidation) and N2O (reduction) simultaneously. One of the great challenges of numerical modeling is determining the appropriate level of complexity when representing the most important environmental controllers. Ignoring complexity, such as simulating microbial processes with only simple Q10 functions, often results in poor model performance, because soil moisture and substrate supply can also be important factors. On the other hand, too much complexity, while perhaps mechanistically compelling, may result in too many poorly constrained parameters. Here we explore a parsimonious modeling framework for consistently integrated mechanistic and mathematical representation of the biophysical processes of belowground GHG production and

  17. A dynamic in vivo-like organotypic blood-brain barrier model to probe metastatic brain tumors

    PubMed Central

    Xu, Hui; Li, Zhongyu; Yu, Yue; Sizdahkhani, Saman; Ho, Winson S.; Yin, Fangchao; Wang, Li; Zhu, Guoli; Zhang, Min; Jiang, Lei; Zhuang, Zhengping; Qin, Jianhua

    2016-01-01

    The blood-brain barrier (BBB) restricts the uptake of many neuro-therapeutic molecules, presenting a formidable hurdle to drug development in brain diseases. We proposed a new and dynamic in vivo-like three-dimensional microfluidic system that replicates the key structural, functional and mechanical properties of the blood-brain barrier in vivo. Multiple factors in this system work synergistically to accentuate BBB-specific attributes–permitting the analysis of complex organ-level responses in both normal and pathological microenvironments in brain tumors. The complex BBB microenvironment is reproduced in this system via physical cell-cell interaction, vascular mechanical cues and cell migration. This model possesses the unique capability to examine brain metastasis of human lung, breast and melanoma cells and their therapeutic responses to chemotherapy. The results suggest that the interactions between cancer cells and astrocytes in BBB microenvironment might affect the ability of malignant brain tumors to traverse between brain and vascular compartments. Furthermore, quantification of spatially resolved barrier functions exists within a single assay, providing a versatile and valuable platform for pharmaceutical development, drug testing and neuroscientific research. PMID:27830712

  18. A dynamic in vivo-like organotypic blood-brain barrier model to probe metastatic brain tumors

    NASA Astrophysics Data System (ADS)

    Xu, Hui; Li, Zhongyu; Yu, Yue; Sizdahkhani, Saman; Ho, Winson S.; Yin, Fangchao; Wang, Li; Zhu, Guoli; Zhang, Min; Jiang, Lei; Zhuang, Zhengping; Qin, Jianhua

    2016-11-01

    The blood-brain barrier (BBB) restricts the uptake of many neuro-therapeutic molecules, presenting a formidable hurdle to drug development in brain diseases. We proposed a new and dynamic in vivo-like three-dimensional microfluidic system that replicates the key structural, functional and mechanical properties of the blood-brain barrier in vivo. Multiple factors in this system work synergistically to accentuate BBB-specific attributes–permitting the analysis of complex organ-level responses in both normal and pathological microenvironments in brain tumors. The complex BBB microenvironment is reproduced in this system via physical cell-cell interaction, vascular mechanical cues and cell migration. This model possesses the unique capability to examine brain metastasis of human lung, breast and melanoma cells and their therapeutic responses to chemotherapy. The results suggest that the interactions between cancer cells and astrocytes in BBB microenvironment might affect the ability of malignant brain tumors to traverse between brain and vascular compartments. Furthermore, quantification of spatially resolved barrier functions exists within a single assay, providing a versatile and valuable platform for pharmaceutical development, drug testing and neuroscientific research.

  19. Dendrimer brain uptake and targeted therapy for brain injury in a large animal model of hypothermic circulatory arrest.

    PubMed

    Mishra, Manoj K; Beaty, Claude A; Lesniak, Wojciech G; Kambhampati, Siva P; Zhang, Fan; Wilson, Mary A; Blue, Mary E; Troncoso, Juan C; Kannan, Sujatha; Johnston, Michael V; Baumgartner, William A; Kannan, Rangaramanujam M

    2014-03-25

    Treatment of brain injury following circulatory arrest is a challenging health issue with no viable therapeutic options. Based on studies in a clinically relevant large animal (canine) model of hypothermic circulatory arrest (HCA)-induced brain injury, neuroinflammation and excitotoxicity have been identified as key players in mediating the brain injury after HCA. Therapy with large doses of valproic acid (VPA) showed some neuroprotection but was associated with adverse side effects. For the first time in a large animal model, we explored whether systemically administered polyamidoamine (PAMAM) dendrimers could be effective in reaching target cells in the brain and deliver therapeutics. We showed that, upon systemic administration, hydroxyl-terminated PAMAM dendrimers are taken up in the brain of injured animals and selectively localize in the injured neurons and microglia in the brain. The biodistribution in other major organs was similar to that seen in small animal models. We studied systemic dendrimer-drug combination therapy with two clinically approved drugs, N-acetyl cysteine (NAC) (attenuating neuroinflammation) and valproic acid (attenuating excitotoxicity), building on positive outcomes in a rabbit model of perinatal brain injury. We prepared and characterized dendrimer-NAC (D-NAC) and dendrimer-VPA (D-VPA) conjugates in multigram quantities. A glutathione-sensitive linker to enable for fast intracellular release. In preliminary efficacy studies, combination therapy with D-NAC and D-VPA showed promise in this large animal model, producing 24 h neurological deficit score improvements comparable to high dose combination therapy with VPA and NAC, or free VPA, but at one-tenth the dose, while significantly reducing the adverse side effects. Since adverse side effects of drugs are exaggerated in HCA, the reduced side effects with dendrimer conjugates and suggestions of neuroprotection offer promise for these nanoscale drug delivery systems.

  20. Functional integration between brain regions at rest occurs in multiple-frequency bands.

    PubMed

    Gohel, Suril R; Biswal, Bharat B

    2015-02-01

    Studies of resting-state fMRI have shown that blood oxygen level dependent (BOLD) signals giving rise to temporal correlation across voxels (or regions) are dominated by low-frequency fluctuations in the range of ∼ 0.01-0.1 Hz. These low-frequency fluctuations have been further divided into multiple distinct frequency bands (slow-5 and -4) based on earlier neurophysiological studies, though low sampling frequency of fMRI (∼ 0.5 Hz) has substantially limited the exploration of other known frequency bands of neurophysiological origins (slow-3, -2, and -1). In this study, we used resting-state fMRI data acquired from 21 healthy subjects at a higher sampling frequency of 1.5 Hz to assess the presence of resting-state functional connectivity (RSFC) across multiple frequency bands: slow-5 to slow-1. The effect of different frequency bands on spatial extent and connectivity strength for known resting-state networks (RSNs) was also evaluated. RSNs were derived using independent component analysis and seed-based correlation. Commonly known RSNs, such as the default mode, the fronto-parietal, the dorsal attention, and the visual networks, were consistently observed at multiple frequency bands. Significant inter-hemispheric connectivity was observed between each seed and its contra lateral brain region across all frequency bands, though overall spatial extent of seed-based correlation maps decreased in slow-2 and slow-1 frequency bands. These results suggest that functional integration between brain regions at rest occurs over multiple frequency bands and RSFC is a multiband phenomenon. These results also suggest that further investigation of BOLD signal in multiple frequency bands for related cognitive processes should be undertaken.

  1. Integrating histology and MRI in the first digital brain of common squirrel monkey, Saimiri sciureus.

    PubMed

    Sun, Peizhen; Parvathaneni, Prasanna; Schilling, Kurt G; Gao, Yurui; Janve, Vaibhav; Anderson, Adam; Landman, Bennett A

    2015-03-17

    This effort is a continuation of development of a digital brain atlas of the common squirrel monkey, Saimiri sciureus, a New World monkey with functional and microstructural organization of central nervous system similar to that of humans. Here, we present the integration of histology with multi-modal magnetic resonance imaging (MRI) atlas constructed from the brain of an adult female squirrel monkey. The central concept of this work is to use block face photography to establish an intermediate common space in coordinate system which preserves the high resolution in-plane resolution of histology while enabling 3-D correspondence with MRI. In vivo MRI acquisitions include high resolution T2 structural imaging (300 µm isotropic) and low resolution diffusion tensor imaging (600 um isotropic). Ex vivo MRI acquisitions include high resolution T2 structural imaging and high resolution diffusion tensor imaging (both 300 µm isotropic). Cortical regions were manually annotated on the co-registered volumes based on published histological sections in-plane. We describe mapping of histology and MRI based data of the common squirrel monkey and construction of a viewing tool that enable online viewing of these datasets. The previously descried atlas MRI is used for its deformation to provide accurate conformation to the MRI, thus adding information at the histological level to the MRI volume. This paper presents the mapping of single 2D image slice in block face as a proof of concept and this can be extended to map the atlas space in 3D coordinate system as part of the future work and can be loaded to an XNAT system for further use.

  2. HERMES: towards an integrated toolbox to characterize functional and effective brain connectivity.

    PubMed

    Niso, Guiomar; Bruña, Ricardo; Pereda, Ernesto; Gutiérrez, Ricardo; Bajo, Ricardo; Maestú, Fernando; del-Pozo, Francisco

    2013-10-01

    The analysis of the interdependence between time series has become an important field of research in the last years, mainly as a result of advances in the characterization of dynamical systems from the signals they produce, the introduction of concepts such as generalized and phase synchronization and the application of information theory to time series analysis. In neurophysiology, different analytical tools stemming from these concepts have added to the 'traditional' set of linear methods, which includes the cross-correlation and the coherency function in the time and frequency domain, respectively, or more elaborated tools such as Granger Causality.This increase in the number of approaches to tackle the existence of functional (FC) or effective connectivity (EC) between two (or among many) neural networks, along with the mathematical complexity of the corresponding time series analysis tools, makes it desirable to arrange them into a unified-easy-to-use software package. The goal is to allow neuroscientists, neurophysiologists and researchers from related fields to easily access and make use of these analysis methods from a single integrated toolbox.Here we present HERMES ( http://hermes.ctb.upm.es ), a toolbox for the Matlab® environment (The Mathworks, Inc), which is designed to study functional and effective brain connectivity from neurophysiological data such as multivariate EEG and/or MEG records. It includes also visualization tools and statistical methods to address the problem of multiple comparisons. We believe that this toolbox will be very helpful to all the researchers working in the emerging field of brain connectivity analysis.

  3. Integrating histology and MRI in the first digital brain of common squirrel monkey, Saimiri sciureus

    NASA Astrophysics Data System (ADS)

    Sun, Peizhen; Parvathaneni, Prasanna; Schilling, Kurt G.; Gao, Yurui; Janve, Vaibhav; Anderson, Adam; Landman, Bennett A.

    2015-03-01

    This effort is a continuation of development of a digital brain atlas of the common squirrel monkey, Saimiri sciureus, a New World monkey with functional and microstructural organization of central nervous system similar to that of humans. Here, we present the integration of histology with multi-modal magnetic resonance imaging (MRI) atlas constructed from the brain of an adult female squirrel monkey. The central concept of this work is to use block face photography to establish an intermediate common space in coordinate system which preserves the high resolution in-plane resolution of histology while enabling 3-D correspondence with MRI. In vivo MRI acquisitions include high resolution T2 structural imaging (300 μm isotropic) and low resolution diffusion tensor imaging (600 um isotropic). Ex vivo MRI acquisitions include high resolution T2 structural imaging and high resolution diffusion tensor imaging (both 300 μm isotropic). Cortical regions were manually annotated on the co-registered volumes based on published histological sections in-plane. We describe mapping of histology and MRI based data of the common squirrel monkey and construction of a viewing tool that enable online viewing of these datasets. The previously descried atlas MRI is used for its deformation to provide accurate conformation to the MRI, thus adding information at the histological level to the MRI volume. This paper presents the mapping of single 2D image slice in block face as a proof of concept and this can be extended to map the atlas space in 3D coordinate system as part of the future work and can be loaded to an XNAT system for further use.

  4. Integrated modelling requires mass collaboration (Invited)

    NASA Astrophysics Data System (ADS)

    Moore, R. V.

    2009-12-01

    add, “and are the plans sustainable?” To return to the present, although, it is now possible to ask the first question and obtain an answer through linked modelling; we are still at a very early stage and the associated uncertainties are large. The process of linking and running linked systems is not yet the simple, reliable process needed for widespread uptake. At this point, it is useful to look back over the development process which has taken us from paper maps to GIS and Google Maps; it was the result of tens of thousands of PhD and MSc projects over forty years. During the development of the OpenMI, it was quickly appreciated that to transform integrated modelling from something possible in a research lab to something that had the ease of use and reliability of Google Maps would require a similar process but on a far greater scale; one far larger than any single organisation or state could support. A dramatic change to the research and development process would be needed. Using the OpenMI Association’s strategy as an example, the presentation will describe how through openness, sharing and mass collaboration made possible by inexpensive communications and computing power and adoption of a minimum set of standards, the innovation and enterprise of thousands of individuals across the world can be brought to bear upon the problems.

  5. Computational modeling of pedunculopontine nucleus deep brain stimulation

    PubMed Central

    Zitella, Laura M.; Mohsenian, Kevin; Pahwa, Mrinal; Gloeckner, Cory; Johnson, Matthew D.

    2013-01-01

    Objective Deep brain stimulation (DBS) near the pedunculopontine nucleus (PPN) has been posited to improve medication-intractable gait and balance problems in patients with Parkinson’s disease. However, clinical studies evaluating this DBS target have not demonstrated consistent therapeutic effects, with several studies reporting the emergence of paresthesia and oculomotor side effects. The spatial and pathway-specific extent to which brainstem regions are modulated during PPN-DBS is not well understood. Approach Here, we describe two computational models that estimate the direct effects of DBS in the PPN region for human and translational non-human primate (NHP) studies. The three-dimensional models were constructed from segmented histological images from each species, multi-compartment neuron models, and inhomogeneous finite element models of the voltage distribution in the brainstem during DBS. Main Results The computational models predicted that: 1) the majority of PPN neurons are activated with −3V monopolar cathodic stimulation; 2) surgical targeting errors of as little as 1 mm in both species decrement activation selectivity; 3) specifically, monopolar stimulation in caudal, medial, or anterior PPN activates a significant proportion of the superior cerebellar peduncle (up to 60% in the human model and 90% in the NHP model at -3V); 4) monopolar stimulation in rostral, lateral, or anterior PPN activates a large percentage of medial lemniscus fibers (up to 33% in the human model and 40% in the NHP model at −3V); and, 5) the current clinical cylindrical electrode design is suboptimal for isolating the modulatory effects to PPN neurons. Significance We show that a DBS lead design with radially-segmented electrodes may yield improved functional outcome for PPN-DBS. PMID:23723145

  6. Computational