Automated Neuropsychological Assessment Metrics (ANAM) Traumatic Brain Injury (TBI): Human Factors Assessment

DTIC Science & Technology

2011-07-01

Lindsay, Cory Overby, Angela Jeter, Petra E. Alfred, Gary L. Boykin, Carita DeVilbiss, and Raymond Bateman ARL-TN-0440 July 2011...Neuropsychological Assessment Metrics (ANAM) Traumatic Brain Injury (TBI): Human Factors Assessment Valerie J. Rice, Petra E. Alfred, Gary L. Boykin...Angela Jeter*, Petra E. Alfred, Gary L. Boykin, Carita DeVilbiss, and Raymond Bateman 5d. PROJECT NUMBER 5e. TASK NUMBER 5f. WORK UNIT

Creating a human brain proteome atlas--13th HUPO BPP Workshop March 30-31, 2010, Ochang, Korea.

PubMed

Gröttrup, Bernd; Stephan, Christian; Marcus, Katrin; Grinberg, Lea T; Wiltfang, Jens; Lee, Sang K; Kim, Young H; Meyer, Helmut E; Park, Young M

2011-07-01

The HUPO Brain Proteome Project (HUPO BPP) held its 13th workshop in Ochang from March 30th to 31st, 2010 prior to the Korean HUPO 10th Annual International Proteomics Conference. The principal aim of this project is to obtain a better understanding of neurodiseases and aging with the ultimate objective of discovering prognostic and diagnostic biomarkers, in addition to the development of novel diagnostic techniques and new medications. The attendees came together to discuss progress in the clinical neuroproteomics of human and to define the needs and guidelines required for more advanced proteomics approaches. Copyright © 2011 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Long-term neural and physiological phenotyping of a single human

PubMed Central

Poldrack, Russell A.; Laumann, Timothy O.; Koyejo, Oluwasanmi; Gregory, Brenda; Hover, Ashleigh; Chen, Mei-Yen; Gorgolewski, Krzysztof J.; Luci, Jeffrey; Joo, Sung Jun; Boyd, Ryan L.; Hunicke-Smith, Scott; Simpson, Zack Booth; Caven, Thomas; Sochat, Vanessa; Shine, James M.; Gordon, Evan; Snyder, Abraham Z.; Adeyemo, Babatunde; Petersen, Steven E.; Glahn, David C.; Reese Mckay, D.; Curran, Joanne E.; Göring, Harald H. H.; Carless, Melanie A.; Blangero, John; Dougherty, Robert; Leemans, Alexander; Handwerker, Daniel A.; Frick, Laurie; Marcotte, Edward M.; Mumford, Jeanette A.

2015-01-01

Psychiatric disorders are characterized by major fluctuations in psychological function over the course of weeks and months, but the dynamic characteristics of brain function over this timescale in healthy individuals are unknown. Here, as a proof of concept to address this question, we present the MyConnectome project. An intensive phenome-wide assessment of a single human was performed over a period of 18 months, including functional and structural brain connectivity using magnetic resonance imaging, psychological function and physical health, gene expression and metabolomics. A reproducible analysis workflow is provided, along with open access to the data and an online browser for results. We demonstrate dynamic changes in brain connectivity over the timescales of days to months, and relations between brain connectivity, gene expression and metabolites. This resource can serve as a testbed to study the joint dynamics of human brain and metabolic function over time, an approach that is critical for the development of precision medicine strategies for brain disorders. PMID:26648521

Spatial Mapping of Structural and Connectional Imaging Data for the Developing Human Brain with Diffusion Tensor Imaging

PubMed Central

Ouyang, Austin; Jeon, Tina; Sunkin, Susan M.; Pletikos, Mihovil; Sedmak, Goran; Sestan, Nenad; Lein, Ed S.; Huang, Hao

2014-01-01

During human brain development from fetal stage to adulthood, the white matter (WM) tracts undergo dramatic changes. Diffusion tensor imaging (DTI), a widely used magnetic resonance imaging (MRI) modality, offers insight into the dynamic changes of WM fibers as these fibers can be noninvasively traced and three-dimensionally (3D) reconstructed with DTI tractography. The DTI and conventional T1 weighted MRI images also provide sufficient cortical anatomical details for mapping the cortical regions of interests (ROIs). In this paper, we described basic concepts and methods of DTI techniques that can be used to trace major WM tracts noninvasively from fetal brain of 14 postconceptional weeks (pcw) to adult brain. We applied these techniques to acquire DTI data and trace, reconstruct and visualize major WM tracts during development. After categorizing major WM fiber bundles into five unique functional tract groups, namely limbic, brain stem, projection, commissural and association tracts, we revealed formation and maturation of these 3D reconstructed WM tracts of the developing human brain. The structural and connectional imaging data offered by DTI provides the anatomical backbone of transcriptional atlas of the developing human brain. PMID:25448302

Dynamic XML-based exchange of relational data: application to the Human Brain Project.

PubMed

Tang, Zhengming; Kadiyska, Yana; Li, Hao; Suciu, Dan; Brinkley, James F

2003-01-01

This paper discusses an approach to exporting relational data in XML format for data exchange over the web. We describe the first real-world application of SilkRoute, a middleware program that dynamically converts existing relational data to a user-defined XML DTD. The application, called XBrain, wraps SilkRoute in a Java Server Pages framework, thus permitting a web-based XQuery interface to a legacy relational database. The application is demonstrated as a query interface to the University of Washington Brain Project's Language Map Experiment Management System, which is used to manage data about language organization in the brain.

The Zagreb Collection of human brains: a unique, versatile, but underexploited resource for the neuroscience community.

PubMed

Judaš, Miloš; Šimić, Goran; Petanjek, Zdravko; Jovanov-Milošević, Nataša; Pletikos, Mihovil; Vasung, Lana; Vukšić, Mario; Kostović, Ivica

2011-05-01

The Zagreb Collection of developing and adult human brains was founded in 1974 by Ivica Kostović and consists of 1,278 developing and adult human brains, including 610 fetal, 317 children, and 359 adult brains. It is one of the largest collections of developing human brains. The collection serves as a key resource for many focused research projects and has led to several seminal contributions on mammalian cortical development, such as the discovery of the transient fetal subplate zone and of early bilaminar synaptogenesis in the embryonic and fetal human cerebral cortex, and the first description of growing afferent pathways in the human fetal telencephalon. The Zagreb Collection also serves as a core resource for ever-growing networks of international collaboration and represents the starting point for many young investigators who now pursue independent research careers at leading international institutions. The Zagreb Collection, however, remains underexploited owing to a lack of adequate funding in Croatia. Funding could establish an online catalog of the collection and modern virtual microscopy scanning methods to make the collection internationally more accessible. © 2011 New York Academy of Sciences.

Pushing spatial and temporal resolution for functional and diffusion MRI in the Human Connectome Project

PubMed Central

Uğurbil, Kamil; Xu, Junqian; Auerbach, Edward J.; Moeller, Steen; Vu, An; Duarte-Carvajalino, Julio M.; Lenglet, Christophe; Wu, Xiaoping; Schmitter, Sebastian; Van de Moortele, Pierre Francois; Strupp, John; Sapiro, Guillermo; De Martino, Federico; Wang, Dingxin; Harel, Noam; Garwood, Michael; Chen, Liyong; Feinberg, David A.; Smith, Stephen M.; Miller, Karla L.; Sotiropoulos, Stamatios N; Jbabdi, Saad; Andersson, Jesper L; Behrens, Timothy EJ; Glasser, Matthew F.; Van Essen, David; Yacoub, Essa

2013-01-01

The human connectome project (HCP) relies primarily on three complementary magnetic resonance (MR) methods. These are: 1) resting state functional MR imaging (rfMRI) which uses correlations in the temporal fluctuations in an fMRI time series to deduce ‘functional connectivity’; 2) diffusion imaging (dMRI), which provides the input for tractography algorithms used for the reconstruction of the complex axonal fiber architecture; and 3) task based fMRI (tfMRI), which is employed to identify functional parcellation in the human brain in order to assist analyses of data obtained with the first two methods. We describe technical improvements and optimization of these methods as well as instrumental choices that impact speed of acquisition of fMRI and dMRI images at 3 Tesla, leading to whole brain coverage with 2 mm isotropic resolution in 0.7 second for fMRI, and 1.25 mm isotropic resolution dMRI data for tractography analysis with three-fold reduction in total data acquisition time. Ongoing technical developments and optimization for acquisition of similar data at 7 Tesla magnetic field are also presented, targeting higher resolution, specificity of functional imaging signals, mitigation of the inhomogeneous radio frequency (RF) fields and power deposition. Results demonstrate that overall, these approaches represent a significant advance in MR imaging of the human brain to investigate brain function and structure. PMID:23702417

Instantaneous brain dynamics mapped to a continuous state space.

PubMed

Billings, Jacob C W; Medda, Alessio; Shakil, Sadia; Shen, Xiaohong; Kashyap, Amrit; Chen, Shiyang; Abbas, Anzar; Zhang, Xiaodi; Nezafati, Maysam; Pan, Wen-Ju; Berman, Gordon J; Keilholz, Shella D

2017-11-15

Measures of whole-brain activity, from techniques such as functional Magnetic Resonance Imaging, provide a means to observe the brain's dynamical operations. However, interpretation of whole-brain dynamics has been stymied by the inherently high-dimensional structure of brain activity. The present research addresses this challenge through a series of scale transformations in the spectral, spatial, and relational domains. Instantaneous multispectral dynamics are first developed from input data via a wavelet filter bank. Voxel-level signals are then projected onto a representative set of spatially independent components. The correlation distance over the instantaneous wavelet-ICA state vectors is a graph that may be embedded onto a lower-dimensional space to assist the interpretation of state-space dynamics. Applying this procedure to a large sample of resting-state and task-active data (acquired through the Human Connectome Project), we segment the empirical state space into a continuum of stimulus-dependent brain states. Upon observing the local neighborhood of brain-states adopted subsequent to each stimulus, we may conclude that resting brain activity includes brain states that are, at times, similar to those adopted during tasks, but that are at other times distinct from task-active brain states. As task-active brain states often populate a local neighborhood, back-projection of segments of the dynamical state space onto the brain's surface reveals the patterns of brain activity that support many experimentally-defined states. Copyright © 2017 Elsevier Inc. All rights reserved.

Human brain MRI at 500 MHz, scientific perspectives and technological challenges

NASA Astrophysics Data System (ADS)

Le Bihan, Denis; Schild, Thierry

2017-03-01

The understanding of the human brain is one of the main scientific challenges of the 21st century. In the early 2000s the French Alternative Energies and Atomic Energy Commission launched a program to conceive and build a ‘human brain explorer’, the first human MRI scanner operating at 11.7 T. This scanner was envisioned to be part of the ambitious French-German project Iseult, bridging together industrial and academic partners to push the limits of molecular neuroimaging, from mouse to man, using ultra-high field MRI. In this article we provide a summary of the main neuroscience and medical targets of the Iseult project, mainly to acquire within timescales compatible with human tolerances images at a scale of 100 μm at which everything remains to discover, and to create new approaches to develop new imaging biomarkers for specific neurological and psychiatric disorders. The system specifications, the technological challenges, in terms of magnet design, winding technology, cryogenics, quench protection, stability control, and the solutions which have been chosen to overcome them and build this outstanding instrument are provided. Lines of the research and development which will be necessary to fully exploit the potential of this and other UHF MRI scanners are also outlined.

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

PubMed

Xia, Mingrui; Wang, Jinhui; He, Yong

2013-01-01

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

A regulatory toolbox of MiniPromoters to drive selective expression in the brain.

PubMed

Portales-Casamar, Elodie; Swanson, Douglas J; Liu, Li; de Leeuw, Charles N; Banks, Kathleen G; Ho Sui, Shannan J; Fulton, Debra L; Ali, Johar; Amirabbasi, Mahsa; Arenillas, David J; Babyak, Nazar; Black, Sonia F; Bonaguro, Russell J; Brauer, Erich; Candido, Tara R; Castellarin, Mauro; Chen, Jing; Chen, Ying; Cheng, Jason C Y; Chopra, Vik; Docking, T Roderick; Dreolini, Lisa; D'Souza, Cletus A; Flynn, Erin K; Glenn, Randy; Hatakka, Kristi; Hearty, Taryn G; Imanian, Behzad; Jiang, Steven; Khorasan-zadeh, Shadi; Komljenovic, Ivana; Laprise, Stéphanie; Liao, Nancy Y; Lim, Jonathan S; Lithwick, Stuart; Liu, Flora; Liu, Jun; Lu, Meifen; McConechy, Melissa; McLeod, Andrea J; Milisavljevic, Marko; Mis, Jacek; O'Connor, Katie; Palma, Betty; Palmquist, Diana L; Schmouth, Jean-François; Swanson, Magdalena I; Tam, Bonny; Ticoll, Amy; Turner, Jenna L; Varhol, Richard; Vermeulen, Jenny; Watkins, Russell F; Wilson, Gary; Wong, Bibiana K Y; Wong, Siaw H; Wong, Tony Y T; Yang, George S; Ypsilanti, Athena R; Jones, Steven J M; Holt, Robert A; Goldowitz, Daniel; Wasserman, Wyeth W; Simpson, Elizabeth M

2010-09-21

The Pleiades Promoter Project integrates genomewide bioinformatics with large-scale knockin mouse production and histological examination of expression patterns to develop MiniPromoters and related tools designed to study and treat the brain by directed gene expression. Genes with brain expression patterns of interest are subjected to bioinformatic analysis to delineate candidate regulatory regions, which are then incorporated into a panel of compact human MiniPromoters to drive expression to brain regions and cell types of interest. Using single-copy, homologous-recombination "knockins" in embryonic stem cells, each MiniPromoter reporter is integrated immediately 5' of the Hprt locus in the mouse genome. MiniPromoter expression profiles are characterized in differentiation assays of the transgenic cells or in mouse brains following transgenic mouse production. Histological examination of adult brains, eyes, and spinal cords for reporter gene activity is coupled to costaining with cell-type-specific markers to define expression. The publicly available Pleiades MiniPromoter Project is a key resource to facilitate research on brain development and therapies.

The Human Genome Project: big science transforms biology and medicine.

PubMed

Hood, Leroy; Rowen, Lee

2013-01-01

The Human Genome Project has transformed biology through its integrated big science approach to deciphering a reference human genome sequence along with the complete sequences of key model organisms. The project exemplifies the power, necessity and success of large, integrated, cross-disciplinary efforts - so-called 'big science' - directed towards complex major objectives. In this article, we discuss the ways in which this ambitious endeavor led to the development of novel technologies and analytical tools, and how it brought the expertise of engineers, computer scientists and mathematicians together with biologists. It established an open approach to data sharing and open-source software, thereby making the data resulting from the project accessible to all. The genome sequences of microbes, plants and animals have revolutionized many fields of science, including microbiology, virology, infectious disease and plant biology. Moreover, deeper knowledge of human sequence variation has begun to alter the practice of medicine. The Human Genome Project has inspired subsequent large-scale data acquisition initiatives such as the International HapMap Project, 1000 Genomes, and The Cancer Genome Atlas, as well as the recently announced Human Brain Project and the emerging Human Proteome Project.

The Human Genome Project: big science transforms biology and medicine

PubMed Central

2013-01-01

The Human Genome Project has transformed biology through its integrated big science approach to deciphering a reference human genome sequence along with the complete sequences of key model organisms. The project exemplifies the power, necessity and success of large, integrated, cross-disciplinary efforts - so-called ‘big science’ - directed towards complex major objectives. In this article, we discuss the ways in which this ambitious endeavor led to the development of novel technologies and analytical tools, and how it brought the expertise of engineers, computer scientists and mathematicians together with biologists. It established an open approach to data sharing and open-source software, thereby making the data resulting from the project accessible to all. The genome sequences of microbes, plants and animals have revolutionized many fields of science, including microbiology, virology, infectious disease and plant biology. Moreover, deeper knowledge of human sequence variation has begun to alter the practice of medicine. The Human Genome Project has inspired subsequent large-scale data acquisition initiatives such as the International HapMap Project, 1000 Genomes, and The Cancer Genome Atlas, as well as the recently announced Human Brain Project and the emerging Human Proteome Project. PMID:24040834

Comprehensive transcriptional map of primate brain development

PubMed Central

Bakken, Trygve E.; Miller, Jeremy A.; Ding, Song-Lin; Sunkin, Susan M.; Smith, Kimberly A.; Ng, Lydia; Szafer, Aaron; Dalley, Rachel A.; Royall, Joshua J.; Lemon, Tracy; Shapouri, Sheila; Aiona, Kaylynn; Arnold, James; Bennett, Jeffrey L.; Bertagnolli, Darren; Bickley, Kristopher; Boe, Andrew; Brouner, Krissy; Butler, Stephanie; Byrnes, Emi; Caldejon, Shiella; Carey, Anita; Cate, Shelby; Chapin, Mike; Chen, Jefferey; Dee, Nick; Desta, Tsega; Dolbeare, Tim A.; Dotson, Nadia; Ebbert, Amanda; Fulfs, Erich; Gee, Garrett; Gilbert, Terri L.; Goldy, Jeff; Gourley, Lindsey; Gregor, Ben; Gu, Guangyu; Hall, Jon; Haradon, Zeb; Haynor, David R.; Hejazinia, Nika; Hoerder-Suabedissen, Anna; Howard, Robert; Jochim, Jay; Kinnunen, Marty; Kriedberg, Ali; Kuan, Chihchau L.; Lau, Christopher; Lee, Chang-Kyu; Lee, Felix; Luong, Lon; Mastan, Naveed; May, Ryan; Melchor, Jose; Mosqueda, Nerick; Mott, Erika; Ngo, Kiet; Nyhus, Julie; Oldre, Aaron; Olson, Eric; Parente, Jody; Parker, Patrick D.; Parry, Sheana; Pendergraft, Julie; Potekhina, Lydia; Reding, Melissa; Riley, Zackery L.; Roberts, Tyson; Rogers, Brandon; Roll, Kate; Rosen, David; Sandman, David; Sarreal, Melaine; Shapovalova, Nadiya; Shi, Shu; Sjoquist, Nathan; Sodt, Andy J.; Townsend, Robbie; Velasquez, Lissette; Wagley, Udi; Wakeman, Wayne B.; White, Cassandra; Bennett, Crissa; Wu, Jennifer; Young, Rob; Youngstrom, Brian L.; Wohnoutka, Paul; Gibbs, Richard A.; Rogers, Jeffrey; Hohmann, John G.; Hawrylycz, Michael J.; Hevner, Robert F.; Molnár, Zoltán; Phillips, John W.; Dang, Chinh; Jones, Allan R.; Amaral, David G.; Bernard, Amy; Lein, Ed S.

2017-01-01

The transcriptional underpinnings of brain development remain poorly understood, particularly in humans and closely related non-human primates. We describe a high resolution transcriptional atlas of rhesus monkey brain development that combines dense temporal sampling of prenatal and postnatal periods with fine anatomical parcellation of cortical and subcortical regions associated with human neuropsychiatric disease. Gene expression changes more rapidly before birth, both in progenitor cells and maturing neurons, and cortical layers and areas acquire adult-like molecular profiles surprisingly late postnatally. Disparate cell populations exhibit distinct developmental timing but also unexpected synchrony of processes underlying neural circuit construction including cell projection and adhesion. Candidate risk genes for neurodevelopmental disorders including primary microcephaly, autism spectrum disorder, intellectual disability, and schizophrenia show disease-specific spatiotemporal enrichment within developing neocortex. Human developmental expression trajectories are more similar to monkey than rodent, and approximately 9% of genes show human-specific regulation with evidence for prolonged maturation or neoteny. PMID:27409810

Connectome imaging for mapping human brain pathways

PubMed Central

Shi, Y; Toga, A W

2017-01-01

With the fast advance of connectome imaging techniques, we have the opportunity of mapping the human brain pathways in vivo at unprecedented resolution. In this article we review the current developments of diffusion magnetic resonance imaging (MRI) for the reconstruction of anatomical pathways in connectome studies. We first introduce the background of diffusion MRI with an emphasis on the technical advances and challenges in state-of-the-art multi-shell acquisition schemes used in the Human Connectome Project. Characterization of the microstructural environment in the human brain is discussed from the tensor model to the general fiber orientation distribution (FOD) models that can resolve crossing fibers in each voxel of the image. Using FOD-based tractography, we describe novel methods for fiber bundle reconstruction and graph-based connectivity analysis. Building upon these novel developments, there have already been successful applications of connectome imaging techniques in reconstructing challenging brain pathways. Examples including retinofugal and brainstem pathways will be reviewed. Finally, we discuss future directions in connectome imaging and its interaction with other aspects of brain imaging research. PMID:28461700

Revealing the cerebello-ponto-hypothalamic pathway in the human brain.

PubMed

Kamali, Arash; Karbasian, Niloofar; Rabiei, Pejman; Cano, Andres; Riascos, Roy F; Tandon, Nitin; Arevalo, Octavio; Ocasio, Laura; Younes, Kyan; Khayat-Khoei, Mahsa; Mirbagheri, Saeedeh; Hasan, Khader M

2018-06-11

The cerebellum is shown to be involved in some limbic functions of the human brain such as emotion and affect. The major connection of the cerebellum with the limbic system is known to be through the cerebello-hypothalamic pathways. The consensus is that the projections from the cerebellar nuclei to the limbic system, and particularly the hypothalamus, or from the hypothalamus to the cerebellar nuclei, are through multisynaptic pathways in the bulbar reticular formation. The detailed anatomy of the pathways responsible for mediating these responses, however, is yet to be determined. Diffusion tensor imaging may be helpful in better visualizing the surgical anatomy of the cerebello-ponto-hypothalamic (CPH) pathway. This study aimed to investigate the utility of high-spatial-resolution diffusion tensor tractography for mapping the trajectory of the CPH tract in the human brain. Fifteen healthy adults were studied. We delineated, for the first time, the detailed trajectory of the CPH tract of the human brain in fifteen normal adult subjects using high-spatial-resolution diffusion tensor tractography. We further revealed the close relationship of the CPH tract with the optic tract, temporo-pontine tract, amygdalofugal tract and the fornix in the human brain. Copyright © 2018 Elsevier B.V. All rights reserved.

Unsupervised Decoding of Long-Term, Naturalistic Human Neural Recordings with Automated Video and Audio Annotations

PubMed Central

Wang, Nancy X. R.; Olson, Jared D.; Ojemann, Jeffrey G.; Rao, Rajesh P. N.; Brunton, Bingni W.

2016-01-01

Fully automated decoding of human activities and intentions from direct neural recordings is a tantalizing challenge in brain-computer interfacing. Implementing Brain Computer Interfaces (BCIs) outside carefully controlled experiments in laboratory settings requires adaptive and scalable strategies with minimal supervision. Here we describe an unsupervised approach to decoding neural states from naturalistic human brain recordings. We analyzed continuous, long-term electrocorticography (ECoG) data recorded over many days from the brain of subjects in a hospital room, with simultaneous audio and video recordings. We discovered coherent clusters in high-dimensional ECoG recordings using hierarchical clustering and automatically annotated them using speech and movement labels extracted from audio and video. To our knowledge, this represents the first time techniques from computer vision and speech processing have been used for natural ECoG decoding. Interpretable behaviors were decoded from ECoG data, including moving, speaking and resting; the results were assessed by comparison with manual annotation. Discovered clusters were projected back onto the brain revealing features consistent with known functional areas, opening the door to automated functional brain mapping in natural settings. PMID:27148018

Alpha-beta and gamma rhythms subserve feedback and feedforward influences among human visual cortical areas

PubMed Central

Michalareas, Georgios; Vezoli, Julien; van Pelt, Stan; Schoffelen, Jan-Mathijs; Kennedy, Henry; Fries, Pascal

2016-01-01

Primate visual cortex is hierarchically organized. Bottom-up and top-down influences are exerted through distinct frequency channels, as was recently revealed in macaques by correlating inter-areal influences with laminar anatomical projection patterns. Because this anatomical data cannot be obtained in human subjects, we selected seven homologous macaque and human visual areas, and correlated the macaque laminar projection patterns to human inter-areal directed influences as measured with magnetoencephalography. We show that influences along feedforward projections predominate in the gamma band, whereas influences along feedback projections predominate in the alpha-beta band. Rhythmic inter-areal influences constrain a functional hierarchy of the seven homologous human visual areas that is in close agreement with the respective macaque anatomical hierarchy. Rhythmic influences allow an extension of the hierarchy to 26 human visual areas including uniquely human brain areas. Hierarchical levels of ventral and dorsal stream visual areas are differentially affected by inter-areal influences in the alpha-beta band. PMID:26777277

On brain activity mapping: insights and lessons from Brain Decoding Project to map memory patterns in the hippocampus.

PubMed

Tsien, Joe Z; Li, Meng; Osan, Remus; Chen, Guifen; Lin, Longnian; Wang, Phillip Lei; Frey, Sabine; Frey, Julietta; Zhu, Dajiang; Liu, Tianming; Zhao, Fang; Kuang, Hui

2013-09-01

The BRAIN project recently announced by the president Obama is the reflection of unrelenting human quest for cracking the brain code, the patterns of neuronal activity that define who we are and what we are. While the Brain Activity Mapping proposal has rightly emphasized on the need to develop new technologies for measuring every spike from every neuron, it might be helpful to consider both the theoretical and experimental aspects that would accelerate our search for the organizing principles of the brain code. Here we share several insights and lessons from the similar proposal, namely, Brain Decoding Project that we initiated since 2007. We provide a specific example in our initial mapping of real-time memory traces from one part of the memory circuit, namely, the CA1 region of the mouse hippocampus. We show how innovative behavioral tasks and appropriate mathematical analyses of large datasets can play equally, if not more, important roles in uncovering the specific-to-general feature-coding cell assembly mechanism by which episodic memory, semantic knowledge, and imagination are generated and organized. Our own experiences suggest that the bottleneck of the Brain Project is not only at merely developing additional new technologies, but also the lack of efficient avenues to disseminate cutting edge platforms and decoding expertise to neuroscience community. Therefore, we propose that in order to harness unique insights and extensive knowledge from various investigators working in diverse neuroscience subfields, ranging from perception and emotion to memory and social behaviors, the BRAIN project should create a set of International and National Brain Decoding Centers at which cutting-edge recording technologies and expertise on analyzing large datasets analyses can be made readily available to the entire community of neuroscientists who can apply and schedule to perform cutting-edge research.

The ALTEA/ALTEINO projects: studying functional effects of microgravity and cosmic radiation

NASA Technical Reports Server (NTRS)

Narici, L.; Belli, F.; Bidoli, V.; Casolino, M.; De Pascale, M. P.; Di Fino, L.; Furano, G.; Modena, I.; Morselli, A.; Picozza, P.;

The ALTEA/ALTEINO projects: studying functional effects of microgravity and cosmic radiation.

PubMed

Narici, L; Belli, F; Bidoli, V; Casolino, M; De Pascale, M P; Di Fino, L; Furano, G; Modena, I; Morselli, A; Picozza, P; Reali, E; Rinaldi, A; Ruggieri, D; Sparvoli, R; Zaconte, V; Sannita, W G; Carozzo, S; Licoccia, S; Romagnoli, P; Traversa, E; Cotronei, V; Vazquez, M; Miller, J; Salnitskii, V P; Shevchenko, O I; Petrov, V P; Trukhanov, K A; Galper, A; Khodarovich, A; Korotkov, M G; Popov, A; Vavilov, N; Avdeev, S; Boezio, M; Bonvicini, W; Vacchi, A; Zampa, N; Mazzenga, G; Ricci, M; Spillantini, P; Castellini, G; Vittori, R; Carlson, P; Fuglesang, C; Schardt, D

2004-01-01

The ALTEA project investigates the risks of functional brain damage induced by particle radiation in space. A modular facility (the ALTEA facility) is being implemented and will be operated in the International Space Station (ISS) to record electrophysiological and behavioral descriptors of brain function and to monitor their time dynamics and correlation with particles and space environment. The focus of the program will be on abnormal visual perceptions (often reported as "light flashes" by astronauts) and the impact on retinal and brain visual structures of particle in microgravity conditions. The facility will be made available to the international scientific community for human neurophysiological, electrophysiological and psychophysics experiments, studies on particle fluxes, and dosimetry. A precursor of ALTEA (the 'Alteino' project) helps set the experimental baseline for the ALTEA experiments, while providing novel information on the radiation environment onboard the ISS and on the brain electrophysiology of the astronauts during orbital flights. Alteino was flown to the ISS on the Soyuz TM34 as part of mission Marco Polo. Controlled ground experiments using mice and accelerator beams complete the experimental strategy of ALTEA. We present here the status of progress of the ALTEA project and preliminary results of the Alteino study on brain dynamics, particle fluxes and abnormal visual perceptions. c2004 COSPAR. Published by Elsevier Ltd. All rights reserved.

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

Big Science, Team Science, and Open Science for Neuroscience.

PubMed

Koch, Christof; Jones, Allan

2016-11-02

The Allen Institute for Brain Science is a non-profit private institution dedicated to basic brain science with an internal organization more commonly found in large physics projects-large teams generating complete, accurate and permanent resources for the mouse and human brain. It can also be viewed as an experiment in the sociology of neuroscience. We here describe some of the singular differences to more academic, PI-focused institutions. Copyright © 2016 Elsevier Inc. All rights reserved.

Oxytocin, brain physiology, and functional connectivity: a review of intranasal oxytocin fMRI studies.

PubMed

Bethlehem, Richard A I; van Honk, Jack; Auyeung, Bonnie; Baron-Cohen, Simon

2013-07-01

In recent years the neuropeptide oxytocin (OT) has become one of the most studied peptides of the human neuroendocrine system. Research has shown widespread behavioural effects and numerous potential therapeutic benefits. However, little is known about how OT triggers these effects in the brain. Here, we discuss some of the physiological properties of OT in the human brain including the long half-life of neuropeptides, the diffuse projections of OT throughout the brain and interactions with other systems such as the dopaminergic system. These properties indicate that OT acts without clear spatial and temporal specificity. Therefore, it is likely to have widespread effects on the brain's intrinsic functioning. Additionally, we review studies that have used functional magnetic resonance imaging (fMRI) concurrently with OT administration. These studies reveal a specific set of 'social' brain regions that are likely to be the strongest targets for OT's potential to influence human behaviour. On the basis of the fMRI literature and the physiological properties of the neuropeptide, we argue that OT has the potential to not only modulate activity in a set of specific brain regions, but also the functional connectivity between these regions. In light of the increasing knowledge of the behavioural effects of OT in humans, studies of the effects of OT administration on brain function can contribute to our understanding of the neural networks in the social brain. Copyright © 2012 Elsevier Ltd. All rights reserved.

A regulatory toolbox of MiniPromoters to drive selective expression in the brain

PubMed Central

Portales-Casamar, Elodie; Swanson, Douglas J.; Liu, Li; de Leeuw, Charles N.; Banks, Kathleen G.; Ho Sui, Shannan J.; Fulton, Debra L.; Ali, Johar; Amirabbasi, Mahsa; Arenillas, David J.; Babyak, Nazar; Black, Sonia F.; Bonaguro, Russell J.; Brauer, Erich; Candido, Tara R.; Castellarin, Mauro; Chen, Jing; Chen, Ying; Cheng, Jason C. Y.; Chopra, Vik; Docking, T. Roderick; Dreolini, Lisa; D'Souza, Cletus A.; Flynn, Erin K.; Glenn, Randy; Hatakka, Kristi; Hearty, Taryn G.; Imanian, Behzad; Jiang, Steven; Khorasan-zadeh, Shadi; Komljenovic, Ivana; Laprise, Stéphanie; Liao, Nancy Y.; Lim, Jonathan S.; Lithwick, Stuart; Liu, Flora; Liu, Jun; Lu, Meifen; McConechy, Melissa; McLeod, Andrea J.; Milisavljevic, Marko; Mis, Jacek; O'Connor, Katie; Palma, Betty; Palmquist, Diana L.; Schmouth, Jean-François; Swanson, Magdalena I.; Tam, Bonny; Ticoll, Amy; Turner, Jenna L.; Varhol, Richard; Vermeulen, Jenny; Watkins, Russell F.; Wilson, Gary; Wong, Bibiana K. Y.; Wong, Siaw H.; Wong, Tony Y. T.; Yang, George S.; Ypsilanti, Athena R.; Jones, Steven J. M.; Holt, Robert A.; Goldowitz, Daniel; Wasserman, Wyeth W.; Simpson, Elizabeth M.

2010-01-01

The Pleiades Promoter Project integrates genomewide bioinformatics with large-scale knockin mouse production and histological examination of expression patterns to develop MiniPromoters and related tools designed to study and treat the brain by directed gene expression. Genes with brain expression patterns of interest are subjected to bioinformatic analysis to delineate candidate regulatory regions, which are then incorporated into a panel of compact human MiniPromoters to drive expression to brain regions and cell types of interest. Using single-copy, homologous-recombination “knockins” in embryonic stem cells, each MiniPromoter reporter is integrated immediately 5′ of the Hprt locus in the mouse genome. MiniPromoter expression profiles are characterized in differentiation assays of the transgenic cells or in mouse brains following transgenic mouse production. Histological examination of adult brains, eyes, and spinal cords for reporter gene activity is coupled to costaining with cell-type–specific markers to define expression. The publicly available Pleiades MiniPromoter Project is a key resource to facilitate research on brain development and therapies. PMID:20807748

Hemispherical map for the human brain cortex

NASA Astrophysics Data System (ADS)

Tosun, Duygu; Prince, Jerry L.

2001-07-01

Understanding the function of the human brain cortex is a primary goal in human brain mapping. Methods to unfold and flatten the cortical surface for visualization and measurement have been described in previous literature; but comparison across multiple subjects is still difficult because of the lack of a standard mapping technique. We describe a new approach that maps each hemisphere of the cortex to a portion of a sphere in a standard way, making comparison of anatomy and function across different subjects possible. Starting with a three-dimensional magnetic resonance image of the brain, the cortex is segmented and represented as a triangle mesh. Defining a cut around the corpus collosum identifies the left and right hemispheres. Together, the two hemispheres are mapped to the complex plane using a conformal mapping technique. A Mobius transformation, which is conformal, is used to transform the points on the complex plane so that a projective transformation maps each brain hemisphere onto a spherical segment comprising a sphere with a cap removed. We determined the best size of the spherical cap by minimizing the relative area distortion between hemispherical maps and original cortical surfaces. The relative area distortion between the hemispherical maps and the original cortical surfaces for fifteen human brains is analyzed.

A Four-Dimensional Probabilistic Atlas of the Human Brain

PubMed Central

Mazziotta, John; Toga, Arthur; Evans, Alan; Fox, Peter; Lancaster, Jack; Zilles, Karl; Woods, Roger; Paus, Tomas; Simpson, Gregory; Pike, Bruce; Holmes, Colin; Collins, Louis; Thompson, Paul; MacDonald, David; Iacoboni, Marco; Schormann, Thorsten; Amunts, Katrin; Palomero-Gallagher, Nicola; Geyer, Stefan; Parsons, Larry; Narr, Katherine; Kabani, Noor; Le Goualher, Georges; Feidler, Jordan; Smith, Kenneth; Boomsma, Dorret; Pol, Hilleke Hulshoff; Cannon, Tyrone; Kawashima, Ryuta; Mazoyer, Bernard

2001-01-01

The authors describe the development of a four-dimensional atlas and reference system that includes both macroscopic and microscopic information on structure and function of the human brain in persons between the ages of 18 and 90 years. Given the presumed large but previously unquantified degree of structural and functional variance among normal persons in the human population, the basis for this atlas and reference system is probabilistic. Through the efforts of the International Consortium for Brain Mapping (ICBM), 7,000 subjects will be included in the initial phase of database and atlas development. For each subject, detailed demographic, clinical, behavioral, and imaging information is being collected. In addition, 5,800 subjects will contribute DNA for the purpose of determining genotype– phenotype–behavioral correlations. The process of developing the strategies, algorithms, data collection methods, validation approaches, database structures, and distribution of results is described in this report. Examples of applications of the approach are described for the normal brain in both adults and children as well as in patients with schizophrenia. This project should provide new insights into the relationship between microscopic and macroscopic structure and function in the human brain and should have important implications in basic neuroscience, clinical diagnostics, and cerebral disorders. PMID:11522763

Big data, open science and the brain: lessons learned from genomics.

PubMed

Choudhury, Suparna; Fishman, Jennifer R; McGowan, Michelle L; Juengst, Eric T

2014-01-01

The BRAIN Initiative aims to break new ground in the scale and speed of data collection in neuroscience, requiring tools to handle data in the magnitude of yottabytes (10(24)). The scale, investment and organization of it are being compared to the Human Genome Project (HGP), which has exemplified "big science" for biology. In line with the trend towards Big Data in genomic research, the promise of the BRAIN Initiative, as well as the European Human Brain Project, rests on the possibility to amass vast quantities of data to model the complex interactions between the brain and behavior and inform the diagnosis and prevention of neurological disorders and psychiatric disease. Advocates of this "data driven" paradigm in neuroscience argue that harnessing the large quantities of data generated across laboratories worldwide has numerous methodological, ethical and economic advantages, but it requires the neuroscience community to adopt a culture of data sharing and open access to benefit from them. In this article, we examine the rationale for data sharing among advocates and briefly exemplify these in terms of new "open neuroscience" projects. Then, drawing on the frequently invoked model of data sharing in genomics, we go on to demonstrate the complexities of data sharing, shedding light on the sociological and ethical challenges within the realms of institutions, researchers and participants, namely dilemmas around public/private interests in data, (lack of) motivation to share in the academic community, and potential loss of participant anonymity. Our paper serves to highlight some foreseeable tensions around data sharing relevant to the emergent "open neuroscience" movement.

The CONNECT project: Combining macro- and micro-structure.

PubMed

Assaf, Yaniv; Alexander, Daniel C; Jones, Derek K; Bizzi, Albero; Behrens, Tim E J; Clark, Chris A; Cohen, Yoram; Dyrby, Tim B; Huppi, Petra S; Knoesche, Thomas R; Lebihan, Denis; Parker, Geoff J M; Poupon, Cyril; Anaby, Debbie; Anwander, Alfred; Bar, Leah; Barazany, Daniel; Blumenfeld-Katzir, Tamar; De-Santis, Silvia; Duclap, Delphine; Figini, Matteo; Fischi, Elda; Guevara, Pamela; Hubbard, Penny; Hofstetter, Shir; Jbabdi, Saad; Kunz, Nicolas; Lazeyras, Francois; Lebois, Alice; Liptrot, Matthew G; Lundell, Henrik; Mangin, Jean-François; Dominguez, David Moreno; Morozov, Darya; Schreiber, Jan; Seunarine, Kiran; Nava, Simone; Poupon, Cyril; Riffert, Till; Sasson, Efrat; Schmitt, Benoit; Shemesh, Noam; Sotiropoulos, Stam N; Tavor, Ido; Zhang, Hui Gary; Zhou, Feng-Lei

2013-10-15

In recent years, diffusion MRI has become an extremely important tool for studying the morphology of living brain tissue, as it provides unique insights into both its macrostructure and microstructure. Recent applications of diffusion MRI aimed to characterize the structural connectome using tractography to infer connectivity between brain regions. In parallel to the development of tractography, additional diffusion MRI based frameworks (CHARMED, AxCaliber, ActiveAx) were developed enabling the extraction of a multitude of micro-structural parameters (axon diameter distribution, mean axonal diameter and axonal density). This unique insight into both tissue microstructure and connectivity has enormous potential value in understanding the structure and organization of the brain as well as providing unique insights to abnormalities that underpin disease states. The CONNECT (Consortium Of Neuroimagers for the Non-invasive Exploration of brain Connectivity and Tracts) project aimed to combine tractography and micro-structural measures of the living human brain in order to obtain a better estimate of the connectome, while also striving to extend validation of these measurements. This paper summarizes the project and describes the perspective of using micro-structural measures to study the connectome. Copyright © 2013 Elsevier Inc. All rights reserved.

Study of the neural dynamics for understanding communication in terms of complex hetero systems.

PubMed

Tsuda, Ichiro; Yamaguchi, Yoko; Hashimoto, Takashi; Okuda, Jiro; Kawasaki, Masahiro; Nagasaka, Yasuo

2015-01-01

The purpose of the research project was to establish a new research area named "neural information science for communication" by elucidating its neural mechanism. The research was performed in collaboration with applied mathematicians in complex-systems science and experimental researchers in neuroscience. The project included measurements of brain activity during communication with or without languages and analyses performed with the help of extended theories for dynamical systems and stochastic systems. The communication paradigm was extended to the interactions between human and human, human and animal, human and robot, human and materials, and even animal and animal. Copyright © 2014 Elsevier Ireland Ltd and the Japan Neuroscience Society. All rights reserved.

Joint explorative analysis of neuroreceptor subsystems in the human brain: application to receptor-transporter correlation using PET data.

PubMed

Cselényi, Zsolt; Lundberg, Johan; Halldin, Christer; Farde, Lars; Gulyás, Balázs

2004-10-01

Positron emission tomography (PET) has proved to be a highly successful technique in the qualitative and quantitative exploration of the human brain's neurotransmitter-receptor systems. In recent years, the number of PET radioligands, targeted to different neuroreceptor systems of the human brain, has increased considerably. This development paves the way for a simultaneous analysis of different receptor systems and subsystems in the same individual. The detailed exploration of the versatility of neuroreceptor systems requires novel technical approaches, capable of operating on huge parametric image datasets. An initial step of such explorative data processing and analysis should be the development of novel exploratory data-mining tools to gain insight into the "structure" of complex multi-individual, multi-receptor data sets. For practical reasons, a possible and feasible starting point of multi-receptor research can be the analysis of the pre- and post-synaptic binding sites of the same neurotransmitter. In the present study, we propose an unsupervised, unbiased data-mining tool for this task and demonstrate its usefulness by using quantitative receptor maps, obtained with positron emission tomography, from five healthy subjects on (pre-synaptic) serotonin transporters (5-HTT or SERT) and (post-synaptic) 5-HT(1A) receptors. Major components of the proposed technique include the projection of the input receptor maps to a feature space, the quasi-clustering and classification of projected data (neighbourhood formation), trans-individual analysis of neighbourhood properties (trajectory analysis), and the back-projection of the results of trajectory analysis to normal space (creation of multi-receptor maps). The resulting multi-receptor maps suggest that complex relationships and tendencies in the relationship between pre- and post-synaptic transporter-receptor systems can be revealed and classified by using this method. As an example, we demonstrate the regional correlation of the serotonin transporter-receptor systems. These parameter-specific multi-receptor maps can usefully guide the researchers in their endeavour to formulate models of multi-receptor interactions and changes in the human brain.

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

PubMed Central

D'Souza, Cletus A; Chopra, Vikramjit; Varhol, Richard; Xie, Yuan-Yun; Bohacec, Slavita; Zhao, Yongjun; Lee, Lisa LC; Bilenky, Mikhail; Portales-Casamar, Elodie; He, An; Wasserman, Wyeth W; Goldowitz, Daniel; Marra, Marco A; Holt, Robert A; Simpson, Elizabeth M; Jones, Steven JM

2008-01-01

Background The Pleiades Promoter Project aims to improve gene therapy by designing human mini-promoters (< 4 kb) that drive gene expression in specific brain regions or cell-types of therapeutic interest. Our goal was to first identify genes displaying regionally enriched expression in the mouse brain so that promoters designed from orthologous human genes can then be tested to drive reporter expression in a similar pattern in the mouse brain. Results We have utilized LongSAGE to identify regionally enriched transcripts in the adult mouse brain. As supplemental strategies, we also performed a meta-analysis of published literature and inspected the Allen Brain Atlas in situ hybridization data. From a set of approximately 30,000 mouse genes, 237 were identified as showing specific or enriched expression in 30 target regions of the mouse brain. GO term over-representation among these genes revealed co-involvement in various aspects of central nervous system development and physiology. Conclusion Using a multi-faceted expression validation approach, we have identified mouse genes whose human orthologs are good candidates for design of mini-promoters. These mouse genes represent molecular markers in several discrete brain regions/cell-types, which could potentially provide a mechanistic explanation of unique functions performed by each region. This set of markers may also serve as a resource for further studies of gene regulatory elements influencing brain expression. PMID:18625066

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

PubMed

D'Souza, Cletus A; Chopra, Vikramjit; Varhol, Richard; Xie, Yuan-Yun; Bohacec, Slavita; Zhao, Yongjun; Lee, Lisa L C; Bilenky, Mikhail; Portales-Casamar, Elodie; He, An; Wasserman, Wyeth W; Goldowitz, Daniel; Marra, Marco A; Holt, Robert A; Simpson, Elizabeth M; Jones, Steven J M

2008-07-14

The Pleiades Promoter Project aims to improve gene therapy by designing human mini-promoters (< 4 kb) that drive gene expression in specific brain regions or cell-types of therapeutic interest. Our goal was to first identify genes displaying regionally enriched expression in the mouse brain so that promoters designed from orthologous human genes can then be tested to drive reporter expression in a similar pattern in the mouse brain. We have utilized LongSAGE to identify regionally enriched transcripts in the adult mouse brain. As supplemental strategies, we also performed a meta-analysis of published literature and inspected the Allen Brain Atlas in situ hybridization data. From a set of approximately 30,000 mouse genes, 237 were identified as showing specific or enriched expression in 30 target regions of the mouse brain. GO term over-representation among these genes revealed co-involvement in various aspects of central nervous system development and physiology. Using a multi-faceted expression validation approach, we have identified mouse genes whose human orthologs are good candidates for design of mini-promoters. These mouse genes represent molecular markers in several discrete brain regions/cell-types, which could potentially provide a mechanistic explanation of unique functions performed by each region. This set of markers may also serve as a resource for further studies of gene regulatory elements influencing brain expression.

Joint penalized-likelihood reconstruction of time-activity curves and regions-of-interest from projection data in brain PET

NASA Astrophysics Data System (ADS)

Krestyannikov, E.; Tohka, J.; Ruotsalainen, U.

2008-06-01

This paper presents a novel statistical approach for joint estimation of regions-of-interest (ROIs) and the corresponding time-activity curves (TACs) from dynamic positron emission tomography (PET) brain projection data. It is based on optimizing the joint objective function that consists of a data log-likelihood term and two penalty terms reflecting the available a priori information about the human brain anatomy. The developed local optimization strategy iteratively updates both the ROI and TAC parameters and is guaranteed to monotonically increase the objective function. The quantitative evaluation of the algorithm is performed with numerically and Monte Carlo-simulated dynamic PET brain data of the 11C-Raclopride and 18F-FDG tracers. The results demonstrate that the method outperforms the existing sequential ROI quantification approaches in terms of accuracy, and can noticeably reduce the errors in TACs arising due to the finite spatial resolution and ROI delineation.

Coexpression networks implicate human midfetal deep cortical projection neurons in the pathogenesis of autism

PubMed Central

Willsey, A. Jeremy; Sanders, Stephan J.; Li, Mingfeng; Dong, Shan; Tebbenkamp, Andrew T.; Muhle, Rebecca A.; Reilly, Steven K.; Lin, Leon; Fertuzinhos, Sofia; Miller, Jeremy A.; Murtha, Michael T.; Bichsel, Candace; Niu, Wei; Cotney, Justin; Ercan-Sencicek, A. Gulhan; Gockley, Jake; Gupta, Abha; Han, Wenqi; He, Xin; Hoffman, Ellen; Klei, Lambertus; Lei, Jing; Liu, Wenzhong; Liu, Li; Lu, Cong; Xu, Xuming; Zhu, Ying; Mane, Shrikant M.; Lein, Edward S.; Wei, Liping; Noonan, James P.; Roeder, Kathryn; Devlin, Bernie; Šestan, Nenad; State, Matthew W.

2013-01-01

SUMMARY Autism spectrum disorder (ASD) is a complex developmental syndrome of unknown etiology. Recent studies employing exome- and genome-wide sequencing have identified nine high-confidence ASD (hcASD) genes. Working from the hypothesis that ASD-associated mutations in these biologically pleiotropic genes will disrupt intersecting developmental processes to contribute to a common phenotype, we have attempted to identify time periods, brain regions, and cell types in which these genes converge. We have constructed coexpression networks based on the hcASD “seed” genes, leveraging a rich expression data set encompassing multiple human brain regions across human development and into adulthood. By assessing enrichment of an independent set of probable ASD (pASD) genes, derived from the same sequencing studies, we demonstrate a key point of convergence in midfetal layer 5/6 cortical projection neurons. This approach informs when, where, and in what cell types mutations in these specific genes may be productively studied to clarify ASD pathophysiology. PMID:24267886

Default, Cognitive and Affective Brain Networks in Human Tinnitus

DTIC Science & Technology

Tinnitus is a major health problem among those currently and formerly in military service. This project hypothesizes that many of the clinically...significant, non-auditory aspects of the tinnitus condition involve two major brain networks: the cognitive control network (CCN) and the default mode...function can be assessed. Subjects in three groups are being compared: (1) control subjects with clinically-normal hearing thresholds and no tinnitus

Progresses in neuroproteomics of neurodegenerative diseases--18th HUPO BPP workshop: September 12, 2012, Boston, USA.

PubMed

Gröttrup, Bernd; May, Caroline; Meyer, Helmut E; Grinberg, Lea T; Park, Young Mok

2013-01-01

The HUPO Brain Proteome Project (HUPO BPP) held its 18(th) workshop in Boston, USA, September 12(th) 2012 during the HUPO 11th Annual Word Congress. The focus was on the progress on the Human Brain Proteome Atlas as well as ideas, strategies and methodological aspects. © 2013 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Challenges in modern biomarker discovery--17th HUPO BPP workshop: May 24-25, 2012, Sao Paulo, Brazil.

PubMed

Gröttrup, Bernd; Esselmann, Hermann; May, Caroline; Schrötter, Andreas; Woitalla, Dirk; Heinsen, Helmut; Marcus, Katrin; Wiltfang, Jens; Meyer, Helmut E; Grinberg, Lea T; Park, Young Mok

2013-01-01

The HUPO Brain Proteome Project (HUPO BPP) held its 17(th) workshop in Sao Paulo, Brazil, on May 24 and 25, 2012. The focus was on the progress on the Human Brain Proteome Atlas as well as ideas, strategies and methodological aspects in clinical neuroproteomics. © 2013 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Translational proteomics in neurodegenerative diseases--16th HUPO BPP workshop September 5, 2011 Geneva, Switzerland.

PubMed

Gröttrup, Bernd; Böckmann, Miriam; Stephan, Christian; Marcus, Katrin; Grinberg, Lea T; Meyer, Helmut E; Park, Young Mok

2012-02-01

The HUPO Brain Proteome Project (HUPO BPP) held its 16th workshop in Geneva, Switzerland, on September 5, 2011 during the 10th HUPO World Congress. The focus was on launching the Human Brain Proteome Atlas as well as ideas, strategies and methodological aspects in clinical neuroproteomics. Copyright © 2012 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

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

PubMed Central

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

2016-01-01

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

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

PubMed

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

2016-01-26

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

Brain-specific enhancers for cell-based therapy

DOE Office of Scientific and Technical Information (OSTI.GOV)

Visel, Axel; Rubenstein, John L.R.; Chen, Ying-Jiun

Herein are described a set of novel specific human enhancers for specific forebrain cell types used to study and select for human neural progenitor cells. This approach enables the ability to generate interneurons from human ES, iPS and iN cells, making them available for human transplantation and for molecular/cellular analyzes. These approaches are also directly applicable to generating other neuronal cell types, such as cortical and striatal projection neurons, which have implications for many human diseases.

Basal ganglia and cerebellar interconnectivity within the human thalamus.

PubMed

Pelzer, Esther A; Melzer, Corina; Timmermann, Lars; von Cramon, D Yves; Tittgemeyer, Marc

2017-01-01

Basal ganglia and the cerebellum are part of a densely interconnected network. While both subcortical structures process information in basically segregated loops that primarily interact in the neocortex, direct subcortical interaction has been recently confirmed by neuroanatomical studies using viral transneuronal tracers in non-human primate brains. The thalamus is thought to be the main relay station of both projection systems. Yet, our understanding of subcortical basal ganglia and cerebellar interconnectivity within the human thalamus is rather sparse, primarily due to limitation in the acquisition of in vivo tracing. Consequently, we strive to characterize projections of both systems and their potential overlap within the human thalamus by diffusion MRI and tractography. Our analysis revealed a decreasing anterior-to-posterior gradient for pallido-thalamic connections in: (1) the ventral-anterior thalamus, (2) the intralaminar nuclei, and (3) midline regions. Conversely, we found a decreasing posterior-to-anterior gradient for dentato-thalamic projections predominantly in: (1) the ventral-lateral and posterior nucleus; (2) dorsal parts of the intralaminar nuclei and the subparafascicular nucleus, and (3) the medioventral and lateral mediodorsal nucleus. A considerable overlap of connectivity pattern was apparent in intralaminar nuclei and midline regions. Notably, pallidal and cerebellar projections were both hemispherically lateralized to the left thalamus. While strikingly consistent with findings from transneuronal studies in non-human primates as well as with pre-existing anatomical studies on developmentally expressed markers or pathological human brains, our assessment provides distinctive connectional fingerprints that illustrate the anatomical substrate of integrated functional networks between basal ganglia and the cerebellum. Thereby, our findings furnish useful implications for cerebellar contributions to the clinical symptomatology of movement disorders.

Design analysis of an MPI human functional brain scanner

PubMed Central

Mason, Erica E.; Cooley, Clarissa Z.; Cauley, Stephen F.; Griswold, Mark A.; Conolly, Steven M.; Wald, Lawrence L.

2017-01-01

MPI’s high sensitivity makes it a promising modality for imaging brain function. Functional contrast is proposed based on blood SPION concentration changes due to Cerebral Blood Volume (CBV) increases during activation, a mechanism utilized in fMRI studies. MPI offers the potential for a direct and more sensitive measure of SPION concentration, and thus CBV, than fMRI. As such, fMPI could surpass fMRI in sensitivity, enhancing the scientific and clinical value of functional imaging. As human-sized MPI systems have not been attempted, we assess the technical challenges of scaling MPI from rodent to human brain. We use a full-system MPI simulator to test arbitrary hardware designs and encoding practices, and we examine tradeoffs imposed by constraints that arise when scaling to human size as well as safety constraints (PNS and central nervous system stimulation) not considered in animal scanners, thereby estimating spatial resolutions and sensitivities achievable with current technology. Using a projection FFL MPI system, we examine coil hardware options and their implications for sensitivity and spatial resolution. We estimate that an fMPI brain scanner is feasible, although with reduced sensitivity (20×) and spatial resolution (5×) compared to existing rodent systems. Nonetheless, it retains sufficient sensitivity and spatial resolution to make it an attractive future instrument for studying the human brain; additional technical innovations can result in further improvements. PMID:28752130

Development of a Finite Element Model for Blast Brain Injury and the Effects of CSF Cavitation

DTIC Science & Technology

2012-02-02

FIGURE 1. Brain geometry from photo ( left ; Visible Human Project) and plane-strain model ( right ). Development of a Finite Element Model method in LS-Dyna...between the non-cavitating ( left ) and cavitating ( right ) models for the 500 kPa/4 ms blast condition. FIGURE 6. (a) Comparing the time-history and (b...between the non-cavitating ( left ) and cavitating ( right ) models for the 500 kPa/4 ms blast condition. PANZER et al. Brain Response to Blast Over the wide

An automatic method of brain tumor segmentation from MRI volume based on the symmetry of brain and level set method

NASA Astrophysics Data System (ADS)

Li, Xiaobing; Qiu, Tianshuang; Lebonvallet, Stephane; Ruan, Su

2010-02-01

This paper presents a brain tumor segmentation method which automatically segments tumors from human brain MRI image volume. The presented model is based on the symmetry of human brain and level set method. Firstly, the midsagittal plane of an MRI volume is searched, the slices with potential tumor of the volume are checked out according to their symmetries, and an initial boundary of the tumor in the slice, in which the tumor is in the largest size, is determined meanwhile by watershed and morphological algorithms; Secondly, the level set method is applied to the initial boundary to drive the curve evolving and stopping to the appropriate tumor boundary; Lastly, the tumor boundary is projected one by one to its adjacent slices as initial boundaries through the volume for the whole tumor. The experiment results are compared with hand tracking of the expert and show relatively good accordance between both.

Segmentation of the Cingulum Bundle in the Human Brain: A New Perspective Based on DSI Tractography and Fiber Dissection Study.

PubMed

Wu, Yupeng; Sun, Dandan; Wang, Yong; Wang, Yibao; Ou, Shaowu

2016-01-01

The cingulum bundle (CB) is a critical white matter fiber tract in the brain, which forms connections between the frontal lobe, parietal lobe and temporal lobe. In non-human primates, the CB is actually divided into distinct subcomponents on the basis of corticocortical connections. However, at present, no study has verified similar distinct subdivisions in the human brain. In this study, we reconstructed these distinct subdivisions in the human brain, and determined their exact cortical connections using high definition fiber tracking (HDFT) technique on 10 healthy adults and a 488-subject template from the Human Connectome Project (HCP-488). Fiber dissections were performed to verify tractography results. Five CB segments were identified. CB-I ran from the subrostral areas to the precuneus and splenium, encircling the corpus callosum (CC). CB-II arched around the splenium and extended anteriorly above the CC to the medial aspect of the superior frontal gyrus (SFG). CB-III connected the superior parietal lobule (SPL) and precuneus with the medial aspect of the SFG. CB-IV was a relatively minor subcomponent from the SPL and precuneus to the frontal region. CB-V, the para-hippocampal cingulum, stemmed from the medial temporal lobe and fanned out to the occipital lobes. Our findings not only provide a more accurate and detailed description on the associated architecture of the subcomponents within the CB, but also offer new insights into the functional role of the CB in the human brain.

Deep brain stimulation, brain maps and personalized medicine: lessons from the human genome project.

PubMed

Fins, Joseph J; Shapiro, Zachary E

2014-01-01

Although the appellation of personalized medicine is generally attributed to advanced therapeutics in molecular medicine, deep brain stimulation (DBS) can also be so categorized. Like its medical counterpart, DBS is a highly personalized intervention that needs to be tailored to a patient's individual anatomy. And because of this, DBS like more conventional personalized medicine, can be highly specific where the object of care is an N = 1. But that is where the similarities end. Besides their differing medical and surgical provenances, these two varieties of personalized medicine have had strikingly different impacts. The molecular variant, though of a more recent vintage has thrived and is experiencing explosive growth, while DBS still struggles to find a sustainable therapeutic niche. Despite its promise, and success as a vetted treatment for drug resistant Parkinson's Disease, DBS has lagged in broadening its development, often encountering regulatory hurdles and financial barriers necessary to mount an adequate number of quality trials. In this paper we will consider why DBS-or better yet neuromodulation-has encountered these challenges and contrast this experience with the more successful advance of personalized medicine. We will suggest that personalized medicine and DBS's differential performance can be explained as a matter of timing and complexity. We believe that DBS has struggled because it has been a journey of scientific exploration conducted without a map. In contrast to molecular personalized medicine which followed the mapping of the human genome and the Human Genome Project, DBS preceded plans for the mapping of the human brain. We believe that this sequence has given personalized medicine a distinct advantage and that the fullest potential of DBS will be realized both as a cartographical or electrophysiological probe and as a modality of personalized medicine.

Advances in diffusion MRI acquisition and processing in the Human Connectome Project

PubMed Central

Sotiropoulos, Stamatios N; Jbabdi, Saad; Xu, Junqian; Andersson, Jesper L; Moeller, Steen; Auerbach, Edward J; Glasser, Matthew F; Hernandez, Moises; Sapiro, Guillermo; Jenkinson, Mark; Feinberg, David A; Yacoub, Essa; Lenglet, Christophe; Ven Essen, David C; Ugurbil, Kamil; Behrens, Timothy EJ

2013-01-01

The Human Connectome Project (HCP) is a collaborative 5-year effort to map human brain connections and their variability in healthy adults. A consortium of HCP investigators will study a population of 1200 healthy adults using multiple imaging modalities, along with extensive behavioral and genetic data. In this overview, we focus on diffusion MRI (dMRI) and the structural connectivity aspect of the project. We present recent advances in acquisition and processing that allow us to obtain very high-quality in-vivo MRI data, while enabling scanning of a very large number of subjects. These advances result from 2 years of intensive efforts in optimising many aspects of data acquisition and processing during the piloting phase of the project. The data quality and methods described here are representative of the datasets and processing pipelines that will be made freely available to the community at quarterly intervals, beginning in 2013. PMID:23702418

Cross-population myelination covariance of human cerebral cortex.

PubMed

Ma, Zhiwei; Zhang, Nanyin

2017-09-01

Cross-population covariance of brain morphometric quantities provides a measure of interareal connectivity, as it is believed to be determined by the coordinated neurodevelopment of connected brain regions. Although useful, structural covariance analysis predominantly employed bulky morphological measures with mixed compartments, whereas studies of the structural covariance of any specific subdivisions such as myelin are rare. Characterizing myelination covariance is of interest, as it will reveal connectivity patterns determined by coordinated development of myeloarchitecture between brain regions. Using myelin content MRI maps from the Human Connectome Project, here we showed that the cortical myelination covariance was highly reproducible, and exhibited a brain organization similar to that previously revealed by other connectivity measures. Additionally, the myelination covariance network shared common topological features of human brain networks such as small-worldness. Furthermore, we found that the correlation between myelination covariance and resting-state functional connectivity (RSFC) was uniform within each resting-state network (RSN), but could considerably vary across RSNs. Interestingly, this myelination covariance-RSFC correlation was appreciably stronger in sensory and motor networks than cognitive and polymodal association networks, possibly due to their different circuitry structures. This study has established a new brain connectivity measure specifically related to axons, and this measure can be valuable to investigating coordinated myeloarchitecture development. Hum Brain Mapp 38:4730-4743, 2017. © 2017 Wiley Periodicals, Inc. © 2017 Wiley Periodicals, Inc.

Fast assembling of neuron fragments in serial 3D sections.

PubMed

Chen, Hanbo; Iascone, Daniel Maxim; da Costa, Nuno Maçarico; Lein, Ed S; Liu, Tianming; Peng, Hanchuan

2017-09-01

Reconstructing neurons from 3D image-stacks of serial sections of thick brain tissue is very time-consuming and often becomes a bottleneck in high-throughput brain mapping projects. We developed NeuronStitcher, a software suite for stitching non-overlapping neuron fragments reconstructed in serial 3D image sections. With its efficient algorithm and user-friendly interface, NeuronStitcher has been used successfully to reconstruct very large and complex human and mouse neurons.

Automated processing pipeline for neonatal diffusion MRI in the developing Human Connectome Project.

PubMed

Bastiani, Matteo; Andersson, Jesper L R; Cordero-Grande, Lucilio; Murgasova, Maria; Hutter, Jana; Price, Anthony N; Makropoulos, Antonios; Fitzgibbon, Sean P; Hughes, Emer; Rueckert, Daniel; Victor, Suresh; Rutherford, Mary; Edwards, A David; Smith, Stephen M; Tournier, Jacques-Donald; Hajnal, Joseph V; Jbabdi, Saad; Sotiropoulos, Stamatios N

2018-05-28

The developing Human Connectome Project is set to create and make available to the scientific community a 4-dimensional map of functional and structural cerebral connectivity from 20 to 44 weeks post-menstrual age, to allow exploration of the genetic and environmental influences on brain development, and the relation between connectivity and neurocognitive function. A large set of multi-modal MRI data from fetuses and newborn infants is currently being acquired, along with genetic, clinical and developmental information. In this overview, we describe the neonatal diffusion MRI (dMRI) image processing pipeline and the structural connectivity aspect of the project. Neonatal dMRI data poses specific challenges, and standard analysis techniques used for adult data are not directly applicable. We have developed a processing pipeline that deals directly with neonatal-specific issues, such as severe motion and motion-related artefacts, small brain sizes, high brain water content and reduced anisotropy. This pipeline allows automated analysis of in-vivo dMRI data, probes tissue microstructure, reconstructs a number of major white matter tracts, and includes an automated quality control framework that identifies processing issues or inconsistencies. We here describe the pipeline and present an exemplar analysis of data from 140 infants imaged at 38-44 weeks post-menstrual age. Copyright © 2018 The Authors. Published by Elsevier Inc. All rights reserved.

Developing Our Human Capital: Results of a Survey of the Education and Business Communities of the Northwest.

ERIC Educational Resources Information Center

National School Public Relations Association. Northwest Region.

Business and education representatives must identify mutual concerns to work together toward the delivery of education. Six regional trends were identified: (1) projections of a shrinking labor supply means untrained youth are a loss of needed human capital; (2) competitive edge increasingly relies on brain power, but students are poorer, more…

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

NASA Astrophysics Data System (ADS)

Wang, Xun-Heng; Li, Lihua

2016-03-01

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

Synaptic inputs from stroke-injured brain to grafted human stem cell-derived neurons activated by sensory stimuli.

PubMed

Tornero, Daniel; Tsupykov, Oleg; Granmo, Marcus; Rodriguez, Cristina; Grønning-Hansen, Marita; Thelin, Jonas; Smozhanik, Ekaterina; Laterza, Cecilia; Wattananit, Somsak; Ge, Ruimin; Tatarishvili, Jemal; Grealish, Shane; Brüstle, Oliver; Skibo, Galina; Parmar, Malin; Schouenborg, Jens; Lindvall, Olle; Kokaia, Zaal

2017-03-01

Transplanted neurons derived from stem cells have been proposed to improve function in animal models of human disease by various mechanisms such as neuronal replacement. However, whether the grafted neurons receive functional synaptic inputs from the recipient's brain and integrate into host neural circuitry is unknown. Here we studied the synaptic inputs from the host brain to grafted cortical neurons derived from human induced pluripotent stem cells after transplantation into stroke-injured rat cerebral cortex. Using the rabies virus-based trans-synaptic tracing method and immunoelectron microscopy, we demonstrate that the grafted neurons receive direct synaptic inputs from neurons in different host brain areas located in a pattern similar to that of neurons projecting to the corresponding endogenous cortical neurons in the intact brain. Electrophysiological in vivo recordings from the cortical implants show that physiological sensory stimuli, i.e. cutaneous stimulation of nose and paw, can activate or inhibit spontaneous activity in grafted neurons, indicating that at least some of the afferent inputs are functional. In agreement, we find using patch-clamp recordings that a portion of grafted neurons respond to photostimulation of virally transfected, channelrhodopsin-2-expressing thalamo-cortical axons in acute brain slices. The present study demonstrates, for the first time, that the host brain regulates the activity of grafted neurons, providing strong evidence that transplanted human induced pluripotent stem cell-derived cortical neurons can become incorporated into injured cortical circuitry. Our findings support the idea that these neurons could contribute to functional recovery in stroke and other conditions causing neuronal loss in cerebral cortex. © The Author (2017). Published by Oxford University Press on behalf of the Guarantors of Brain. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

Straight talk with...Miyoung Chun. Interview by Virginia Hughes.

PubMed

Chun, Miyoung

2013-04-01

It was a single tweet. In February, after US President Barack Obama made a subtle nod to a new neuroscience project in his annual State of the Union address, Francis Collins, director of the country's National Institutes of Health (NIH), posted on the @NIHDirector Twitter feed: "Obama mentions the #NIH Brain Activity Map in #SOTU." Instantly, scientists were buzzing with rumors that the Brain Activity Map could be the next moon shot, with a budget and timeline similar to the Human Genome Project. The brain map began as a brief white paper and has grown into a large--and still largely undefined--collaboration of several government agencies, nonprofit foundations and private companies. As the stakeholders describe in a commentary published last month (339, 1284-1285, 2013), the goal of the initiative is to understand how thousands of neurons work in concert to control behavior and trigger disease. Miyoung Chun, vice president for science programs at The Kavli Foundation in Oxnard, California, has been developing the project since the beginning and is the self-described "glue" between its many diverse stakeholders. Chun spoke with Virginia Hughes about the evolution of the project and what it might mean for biomedicine.

Anatomical accuracy of brain connections derived from diffusion MRI tractography is inherently limited.

PubMed

Thomas, Cibu; Ye, Frank Q; Irfanoglu, M Okan; Modi, Pooja; Saleem, Kadharbatcha S; Leopold, David A; Pierpaoli, Carlo

2014-11-18

Tractography based on diffusion-weighted MRI (DWI) is widely used for mapping the structural connections of the human brain. Its accuracy is known to be limited by technical factors affecting in vivo data acquisition, such as noise, artifacts, and data undersampling resulting from scan time constraints. It generally is assumed that improvements in data quality and implementation of sophisticated tractography methods will lead to increasingly accurate maps of human anatomical connections. However, assessing the anatomical accuracy of DWI tractography is difficult because of the lack of independent knowledge of the true anatomical connections in humans. Here we investigate the future prospects of DWI-based connectional imaging by applying advanced tractography methods to an ex vivo DWI dataset of the macaque brain. The results of different tractography methods were compared with maps of known axonal projections from previous tracer studies in the macaque. Despite the exceptional quality of the DWI data, none of the methods demonstrated high anatomical accuracy. The methods that showed the highest sensitivity showed the lowest specificity, and vice versa. Additionally, anatomical accuracy was highly dependent upon parameters of the tractography algorithm, with different optimal values for mapping different pathways. These results suggest that there is an inherent limitation in determining long-range anatomical projections based on voxel-averaged estimates of local fiber orientation obtained from DWI data that is unlikely to be overcome by improvements in data acquisition and analysis alone.

Brain Computer Interfaces for Enhanced Interaction with Mobile Robot Agents

DTIC Science & Technology

2016-07-27

synergistic and complementary way. This project focused on acquiring a mobile robotic agent platform that can be used to explore these interfaces...providing a test environment where the human control of a robot agent can be experimentally validated in 1. REPORT DATE (DD-MM-YYYY) 4. TITLE AND...Distribution Unlimited UU UU UU UU 27-07-2016 17-Sep-2013 16-Sep-2014 Final Report: Brain Computer Interfaces for Enhanced Interactions with Mobile Robot

The topology of large Open Connectome networks for the human brain.

PubMed

Gastner, Michael T; Ódor, Géza

2016-06-07

The structural human connectome (i.e. the network of fiber connections in the brain) can be analyzed at ever finer spatial resolution thanks to advances in neuroimaging. Here we analyze several large data sets for the human brain network made available by the Open Connectome Project. We apply statistical model selection to characterize the degree distributions of graphs containing up to nodes and edges. A three-parameter generalized Weibull (also known as a stretched exponential) distribution is a good fit to most of the observed degree distributions. For almost all networks, simple power laws cannot fit the data, but in some cases there is statistical support for power laws with an exponential cutoff. We also calculate the topological (graph) dimension D and the small-world coefficient σ of these networks. While σ suggests a small-world topology, we found that D < 4 showing that long-distance connections provide only a small correction to the topology of the embedding three-dimensional space.

The topology of large Open Connectome networks for the human brain

NASA Astrophysics Data System (ADS)

Gastner, Michael T.; Ódor, Géza

2016-06-01

The structural human connectome (i.e. the network of fiber connections in the brain) can be analyzed at ever finer spatial resolution thanks to advances in neuroimaging. Here we analyze several large data sets for the human brain network made available by the Open Connectome Project. We apply statistical model selection to characterize the degree distributions of graphs containing up to nodes and edges. A three-parameter generalized Weibull (also known as a stretched exponential) distribution is a good fit to most of the observed degree distributions. For almost all networks, simple power laws cannot fit the data, but in some cases there is statistical support for power laws with an exponential cutoff. We also calculate the topological (graph) dimension D and the small-world coefficient σ of these networks. While σ suggests a small-world topology, we found that D < 4 showing that long-distance connections provide only a small correction to the topology of the embedding three-dimensional space.

Neuropsychology and cognitive neuroscience in the fMRI era: A recapitulation of localizationist and connectionist views.

PubMed

Sutterer, Matthew J; Tranel, Daniel

2017-11-01

We highlight the past 25 years of cognitive neuroscience and neuropsychology, focusing on the impact to the field of the introduction in 1992 of functional MRI (fMRI). We reviewed the past 25 years of literature in cognitive neuroscience and neuropsychology, focusing on the relation and interplay of fMRI studies and studies utilizing the "lesion method" in human participants with focal brain damage. Our review highlights the state of localist/connectionist research debates in cognitive neuroscience and neuropsychology circa 1992, and details how the introduction of fMRI into the field at that time catalyzed a new wave of efforts to map complex human behavior to specific brain regions. This, in turn, eventually evolved into many studies that focused on networks and connections between brain areas, culminating in recent years with large-scale investigations such as the Human Connectome Project. We argue that throughout the past 25 years, neuropsychology-and more precisely, the "lesion method" in humans-has continued to play a critical role in arbitrating conclusions and theories derived from inferred patterns of local brain activity or wide-spread connectivity from functional imaging approaches. We conclude by highlighting the future for neuropsychology in the context of an increasingly complex methodological armamentarium. (PsycINFO Database Record (c) 2018 APA, all rights reserved).

Future of Mechatronics and Human

NASA Astrophysics Data System (ADS)

Harashima, Fumio; Suzuki, Satoshi

This paper mentions circumstance of mechatronics that sustain our human society, and introduces HAM(Human Adaptive Mechatronics)-project as one of research projects to create new human-machine system. The key point of HAM is skill, and analysis of skill and establishment of assist method to enhance total performance of human-machine system are main research concerns. As study of skill is an elucidation of human itself, analyses of human higher function are significant. In this paper, after surveying researches of human brain functions, an experimental analysis of human characteristic in machine operation is shown as one example of our research activities. We used hovercraft simulator as verification system including observation, voluntary motion control and machine operation that are needed to general machine operation. Process and factors to become skilled were investigated by identification of human control characteristics with measurement of the operator's line-of sight. It was confirmed that early switching of sub-controllers / reference signals in human and enhancement of space perception are significant.

Mapping population-based structural connectomes.

PubMed

Zhang, Zhengwu; Descoteaux, Maxime; Zhang, Jingwen; Girard, Gabriel; Chamberland, Maxime; Dunson, David; Srivastava, Anuj; Zhu, Hongtu

2018-05-15

Advances in understanding the structural connectomes of human brain require improved approaches for the construction, comparison and integration of high-dimensional whole-brain tractography data from a large number of individuals. This article develops a population-based structural connectome (PSC) mapping framework to address these challenges. PSC simultaneously characterizes a large number of white matter bundles within and across different subjects by registering different subjects' brains based on coarse cortical parcellations, compressing the bundles of each connection, and extracting novel connection weights. A robust tractography algorithm and streamline post-processing techniques, including dilation of gray matter regions, streamline cutting, and outlier streamline removal are applied to improve the robustness of the extracted structural connectomes. The developed PSC framework can be used to reproducibly extract binary networks, weighted networks and streamline-based brain connectomes. We apply the PSC to Human Connectome Project data to illustrate its application in characterizing normal variations and heritability of structural connectomes in healthy subjects. Copyright © 2018 Elsevier Inc. All rights reserved.

Toward a 3D model of human brain development for studying gene/environment interactions

PubMed Central

2013-01-01

This project aims to establish and characterize an in vitro model of the developing human brain for the purpose of testing drugs and chemicals. To accurately assess risk, a model needs to recapitulate the complex interactions between different types of glial cells and neurons in a three-dimensional platform. Moreover, human cells are preferred over cells from rodents to eliminate cross-species differences in sensitivity to chemicals. Previously, we established conditions to culture rat primary cells as three-dimensional aggregates, which will be humanized and evaluated here with induced pluripotent stem cells (iPSCs). The use of iPSCs allows us to address gene/environment interactions as well as the potential of chemicals to interfere with epigenetic mechanisms. Additionally, iPSCs afford us the opportunity to study the effect of chemicals during very early stages of brain development. It is well recognized that assays for testing toxicity in the developing brain must consider differences in sensitivity and susceptibility that arise depending on the time of exposure. This model will reflect critical developmental processes such as proliferation, differentiation, lineage specification, migration, axonal growth, dendritic arborization and synaptogenesis, which will probably display differences in sensitivity to different types of chemicals. Functional endpoints will evaluate the complex cell-to-cell interactions that are affected in neurodevelopment through chemical perturbation, and the efficacy of drug intervention to prevent or reverse phenotypes. The model described is designed to assess developmental neurotoxicity effects on unique processes occurring during human brain development by leveraging human iPSCs from diverse genetic backgrounds, which can be differentiated into different cell types of the central nervous system. Our goal is to demonstrate the feasibility of the personalized model using iPSCs derived from individuals with neurodevelopmental disorders caused by known mutations and chromosomal aberrations. Notably, such a human brain model will be a versatile tool for more complex testing platforms and strategies as well as research into central nervous system physiology and pathology. PMID:24564953

Prominent periventricular fiber system related to ganglionic eminence and striatum in the human fetal cerebrum.

PubMed

Vasung, L; Jovanov-Milošević, N; Pletikos, M; Mori, S; Judaš, M; Kostović, Ivica

2011-01-01

Periventricular pathway (PVP) system of the developing human cerebrum is situated medial to the intermediate zone in the close proximity to proliferative cell compartments. In order to elucidate chemical properties and developing trajectories of the PVP we used DTI in combination with acetylcholinesterase histochemistry, SNAP-25 immunocytochemistry and axonal cytoskeletal markers (SMI312, MAP1b) immunocytochemistry on postmortem paraformaldehyde-fixed brains of 30 human fetuses ranging in age from 10 to 38 postconceptional weeks (PCW), 2 infants (age 1-3 months) and 1 adult brain. The PVP appears in the early fetal period (10-13 PCW) as two defined fibre bundles: the corpus callosum (CC) and the fetal fronto-occipital fascicle (FOF). In the midfetal period (15-18 PCW), all four components of the PVP can be identified: (1) the CC, which at rostral levels forms a voluminous callosal plate; (2) the FOF, with SNAP-25-positive fibers; (3) the fronto-pontine pathway (FPP) which for a short distance runs within the PVP; and (4) the subcallosal fascicle of Muratoff (SFM) which contains cortico-caudate projections. The PVPs are situated medial to the internal capsule at the level of the cortico-striatal junction; they remain prominent during the late fetal and early preterm period (19-28 PCW) and represent a portion of the wider periventricular crossroad of growing associative, callosal and projection pathways. In the perinatal period, the PVPs change their topographical relationships, decrease in size and the FOF looses its SNAP-25-reactivity. In conclusion, the hitherto undescribed PVP of the human fetal cerebrum contains forerunners of adult associative and projection pathways. Its transient chemical properties and relative exuberance suggest that the PVP may exert influence on the development of cortical connectivity (intermediate targeting) and other neurogenetic events such as neuronal proliferation. The PVP's topographical position also indicates that it is a major site of vulnerability in hypoxic-ischaemic perinatal brain injury. © Springer-Verlag 2010

Large-scale topology and the default mode network in the mouse connectome

PubMed Central

Stafford, James M.; Jarrett, Benjamin R.; Miranda-Dominguez, Oscar; Mills, Brian D.; Cain, Nicholas; Mihalas, Stefan; Lahvis, Garet P.; Lattal, K. Matthew; Mitchell, Suzanne H.; David, Stephen V.; Fryer, John D.; Nigg, Joel T.; Fair, Damien A.

2014-01-01

Noninvasive functional imaging holds great promise for serving as a translational bridge between human and animal models of various neurological and psychiatric disorders. However, despite a depth of knowledge of the cellular and molecular underpinnings of atypical processes in mouse models, little is known about the large-scale functional architecture measured by functional brain imaging, limiting translation to human conditions. Here, we provide a robust processing pipeline to generate high-resolution, whole-brain resting-state functional connectivity MRI (rs-fcMRI) images in the mouse. Using a mesoscale structural connectome (i.e., an anterograde tracer mapping of axonal projections across the mouse CNS), we show that rs-fcMRI in the mouse has strong structural underpinnings, validating our procedures. We next directly show that large-scale network properties previously identified in primates are present in rodents, although they differ in several ways. Last, we examine the existence of the so-called default mode network (DMN)—a distributed functional brain system identified in primates as being highly important for social cognition and overall brain function and atypically functionally connected across a multitude of disorders. We show the presence of a potential DMN in the mouse brain both structurally and functionally. Together, these studies confirm the presence of basic network properties and functional networks of high translational importance in structural and functional systems in the mouse brain. This work clears the way for an important bridge measurement between human and rodent models, enabling us to make stronger conclusions about how regionally specific cellular and molecular manipulations in mice relate back to humans. PMID:25512496

The macro-structural variability of the human neocortex.

PubMed

Kruggel, Frithjof

2018-05-15

The human neocortex shows a considerable individual structural variability. While primary gyri and sulci are found in all normally developed brains and bear clear-cut gross structural descriptions, secondary structures are highly variable and not present in all brains. The blend of common and individual structures poses challenges when comparing structural and functional results from quantitative neuroimaging studies across individuals, and sets limits on the precision of location information much above the spatial resolution of current neuroimaging methods. This work aimed at quantifying structural variability on the neocortex, and at assessing the spatial relationship between regions common to all brains and their individual structural variants. Based on structural MRI data provided as the "900 Subjects Release" of the Human Connectome Project, a data-driven analytic approach was employed here from which the definition of seven cortical "communities" emerged. Apparently, these communities comprise common regions of structural features, while the individual variability is confined within a community. Similarities between the community structure and the state of the brain development at gestation week 32 lead suggest that communities are segregated early. Subdividing the neocortex into communities is suggested as anatomically more meaningful than the traditional lobar structure. Copyright © 2018 Elsevier Inc. All rights reserved.

Hierarchical Topological Network Analysis of Anatomical Human Brain Connectivity and Differences Related to Sex and Kinship

DTIC Science & Technology

2011-10-01

Richiardi, J., Eryilmaz, H., Schwartz, S ., Vuilleumier, P., Van De Ville, D.,1499 2010. Decoding brain states from fmri connectivity graphs. Neuroimage1500...Differences Related to Sex and Kinship 5a. CONTRACT NUMBER 5b. GRANT NUMBER 5c. PROGRAM ELEMENT NUMBER 6. AUTHOR( S ) 5d. PROJECT NUMBER 5e. TASK NUMBER...5f. WORK UNIT NUMBER 7. PERFORMING ORGANIZATION NAME( S ) AND ADDRESS(ES) University of Minnesota,Institute for Mathematics and Its Applications,207

Extending the mind: a review of ethnographies of neuroscience practice.

PubMed

Mahfoud, Tara

2014-01-01

THIS PAPER REVIEWS ETHNOGRAPHIES OF NEUROSCIENCE LABORATORIES IN THE UNITED STATES AND EUROPE, ORGANIZING THEM INTO THREE MAIN SECTIONS: (1) descriptions of the capabilities and limitations of technologies used in neuroimaging laboratories to map "activity" or "function" onto structural models of the brain; (2) discussions of the "distributed" or "extended" mind in neuroscience practice; and (3) the implications of neuroscience research and the power of brain images outside the laboratory. I will try to show the importance of ethnographic work in such settings, and place this body of ethnographic work within its historical framework-such ethnographies largely emerged within the Decade of the Brain, as announced by former President of the United States George H. W. Bush in 1990. The main argument is that neuroscience research and the context within which it is taking place has changed since the 1990's-specifically with the launch of "big science" projects such as the Human Brain Project (HBP) in the European Union and the BRAIN initiative in the United States. There is an opportunity for more research into the institutional and politico-economic context within which neuroscience research is taking place, and for continued engagement between the social and biological sciences.

Dedicated mobile volumetric cone-beam computed tomography for human brain imaging: A phantom study.

PubMed

Ryu, Jong-Hyun; Kim, Tae-Hoon; Jeong, Chang-Won; Jun, Hong-Young; Heo, Dong-Woon; Lee, Jinseok; Kim, Kyong-Woo; Yoon, Kwon-Ha

2015-01-01

Mobile computed tomography (CT) with a cone-beam source is increasingly used in the clinical field. Mobile cone-beam CT (CBCT) has great merits; however, its clinical utility for brain imaging has been limited due to problems including scan time and image quality. The aim of this study was to develop a dedicated mobile volumetric CBCT for obtaining brain images, and to optimize the imaging protocol using a brain phantom. The mobile volumetric CBCT system was evaluated with regards to scan time and image quality, measured as signal-to-noise-ratio (SNR), contrast-to-noise-ratio (CNR), spatial resolution (10% MTF), and effective dose. Brain images were obtained using a CT phantom. The CT scan took 5.14 s at 360 projection views. SNR and CNR were 5.67 and 14.5 at 120 kV/10 mA. SNR and CNR values showed slight improvement as the x-ray voltage and current increased (p < 0.001). Effective dose and 10% MTF were 0.92 mSv and 360 μ m at 120 kV/10 mA. Various intracranial structures were clearly visible in the brain phantom images. Using this CBCT under optimal imaging acquisition conditions, it is possible to obtain human brain images with low radiation dose, reproducible image quality, and fast scan time.

Chronnectome fingerprinting: Identifying individuals and predicting higher cognitive functions using dynamic brain connectivity patterns.

PubMed

Liu, Jin; Liao, Xuhong; Xia, Mingrui; He, Yong

2018-02-01

The human brain is a large, interacting dynamic network, and its architecture of coupling among brain regions varies across time (termed the "chronnectome"). However, very little is known about whether and how the dynamic properties of the chronnectome can characterize individual uniqueness, such as identifying individuals as a "fingerprint" of the brain. Here, we employed multiband resting-state functional magnetic resonance imaging data from the Human Connectome Project (N = 105) and a sliding time-window dynamic network analysis approach to systematically examine individual time-varying properties of the chronnectome. We revealed stable and remarkable individual variability in three dynamic characteristics of brain connectivity (i.e., strength, stability, and variability), which was mainly distributed in three higher order cognitive systems (i.e., default mode, dorsal attention, and fronto-parietal) and in two primary systems (i.e., visual and sensorimotor). Intriguingly, the spatial patterns of these dynamic characteristics of brain connectivity could successfully identify individuals with high accuracy and could further significantly predict individual higher cognitive performance (e.g., fluid intelligence and executive function), which was primarily contributed by the higher order cognitive systems. Together, our findings highlight that the chronnectome captures inherent functional dynamics of individual brain networks and provides implications for individualized characterization of health and disease. © 2017 Wiley Periodicals, Inc.

The HUPO Brain Proteome project wish list--summary of the 9(th) HUPO BPP Workshop 9-10 January 2008, Barbados.

PubMed

Hamacher, Michael; Eisenacher, Martin; Tribl, Florian; Stephan, Christian; Marcus, Katrin; Hardt, Tanja; Wiltfang, Jens; Martens, Lennart; Desiderio, Dominic; Gutstein, Howard; Park, Young Mok; Meyer, Helmut E

2008-06-01

The Human Brain Proteome Project (HUPO BPP) aims at advancing knowledge and the understanding of neurodiseases and aging with the purpose of identifying prognostic and diagnostic biomarkers, as well as to push new diagnostic approaches and medications. The participating groups meet in semi-annual workshops to discuss the progress, as well as the needs, within the field of proteomics. The 9(th) HUPO BPP workshop took place in Barbados from 9-10 January, 2008. Discussing the future HUPO BPP Roadmap, the attendees drafted the so called HUPO BPP wish list containing timelines, suggestions and missions. This wish list will be updated regularly and will serve as a guideline for the next phase.

The braingraph.org database of high resolution structural connectomes and the brain graph tools.

PubMed

Kerepesi, Csaba; Szalkai, Balázs; Varga, Bálint; Grolmusz, Vince

2017-10-01

Based on the data of the NIH-funded Human Connectome Project, we have computed structural connectomes of 426 human subjects in five different resolutions of 83, 129, 234, 463 and 1015 nodes and several edge weights. The graphs are given in anatomically annotated GraphML format that facilitates better further processing and visualization. For 96 subjects, the anatomically classified sub-graphs can also be accessed, formed from the vertices corresponding to distinct lobes or even smaller regions of interests of the brain. For example, one can easily download and study the connectomes, restricted to the frontal lobes or just to the left precuneus of 96 subjects using the data. Partially directed connectomes of 423 subjects are also available for download. We also present a GitHub-deposited set of tools, called the Brain Graph Tools, for several processing tasks of the connectomes on the site http://braingraph.org.

The UNC/UMN Baby Connectome Project (BCP): An overview of the study design and protocol development.

PubMed

Howell, Brittany R; Styner, Martin A; Gao, Wei; Yap, Pew-Thian; Wang, Li; Baluyot, Kristine; Yacoub, Essa; Chen, Geng; Potts, Taylor; Salzwedel, Andrew; Li, Gang; Gilmore, John H; Piven, Joseph; Smith, J Keith; Shen, Dinggang; Ugurbil, Kamil; Zhu, Hongtu; Lin, Weili; Elison, Jed T

2018-03-22

The human brain undergoes extensive and dynamic growth during the first years of life. The UNC/UMN Baby Connectome Project (BCP), one of the Lifespan Connectome Projects funded by NIH, is an ongoing study jointly conducted by investigators at the University of North Carolina at Chapel Hill and the University of Minnesota. The primary objective of the BCP is to characterize brain and behavioral development in typically developing infants across the first 5 years of life. The ultimate goals are to chart emerging patterns of structural and functional connectivity during this period, map brain-behavior associations, and establish a foundation from which to further explore trajectories of health and disease. To accomplish these goals, we are combining state of the art MRI acquisition and analysis techniques, including high-resolution structural MRI (T1-and T2-weighted images), diffusion imaging (dMRI), and resting state functional connectivity MRI (rfMRI). While the overall design of the BCP largely is built on the protocol developed by the Lifespan Human Connectome Project (HCP), given the unique age range of the BCP cohort, additional optimization of imaging parameters and consideration of an age appropriate battery of behavioral assessments were needed. Here we provide the overall study protocol, including approaches for subject recruitment, strategies for imaging typically developing children 0-5 years of age without sedation, imaging protocol and optimization, a description of the battery of behavioral assessments, and QA/QC procedures. Combining HCP inspired neuroimaging data with well-established behavioral assessments during this time period will yield an invaluable resource for the scientific community. Copyright © 2018 Elsevier Inc. All rights reserved.

Schizotypal Perceptual Aberrations of Time: Correlation between Score, Behavior and Brain Activity

PubMed Central

Arzy, Shahar; Mohr, Christine; Molnar-Szakacs, Istvan; Blanke, Olaf

2011-01-01

A fundamental trait of the human self is its continuum experience of space and time. Perceptual aberrations of this spatial and temporal continuity is a major characteristic of schizophrenia spectrum disturbances – including schizophrenia, schizotypal personality disorder and schizotypy. We have previously found the classical Perceptual Aberration Scale (PAS) scores, related to body and space, to be positively correlated with both behavior and temporo-parietal activation in healthy participants performing a task involving self-projection in space. However, not much is known about the relationship between temporal perceptual aberration, behavior and brain activity. To this aim, we composed a temporal Perceptual Aberration Scale (tPAS) similar to the traditional PAS. Testing on 170 participants suggested similar performance for PAS and tPAS. We then correlated tPAS and PAS scores to participants' performance and neural activity in a task of self-projection in time. tPAS scores correlated positively with reaction times across task conditions, as did PAS scores. Evoked potential mapping and electrical neuroimaging showed self-projection in time to recruit a network of brain regions at the left anterior temporal cortex, right temporo-parietal junction, and occipito-temporal cortex, and duration of activation in this network positively correlated with tPAS and PAS scores. These data demonstrate that schizotypal perceptual aberrations of both time and space, as reflected by tPAS and PAS scores, are positively correlated with performance and brain activation during self-projection in time in healthy individuals along the schizophrenia spectrum. PMID:21267456

Evolution of the cerebellar cortex: the selective expansion of prefrontal-projecting cerebellar lobules.

PubMed

Balsters, J H; Cussans, E; Diedrichsen, J; Phillips, K A; Preuss, T M; Rilling, J K; Ramnani, N

2010-02-01

It has been suggested that interconnected brain areas evolve in tandem because evolutionary pressures act on complete functional systems rather than on individual brain areas. The cerebellar cortex has reciprocal connections with both the prefrontal cortex and motor cortex, forming independent loops with each. Specifically, in capuchin monkeys cerebellar cortical lobules Crus I and Crus II connect with prefrontal cortex, whereas the primary motor cortex connects with cerebellar lobules V, VI, VIIb, and VIIIa. Comparisons of extant primate species suggest that the prefrontal cortex has expanded more than cortical motor areas in human evolution. Given the enlargement of the prefrontal cortex relative to motor cortex in humans, our hypothesis would predict corresponding volumetric increases in the parts of the cerebellum connected to the prefrontal cortex, relative to cerebellar lobules connected to the motor cortex. We tested the hypothesis by comparing the volumes of cerebellar lobules in structural MRI scans in capuchins, chimpanzees and humans. The fractions of cerebellar volume occupied by Crus I and Crus II were significantly larger in humans compared to chimpanzees and capuchins. Our results therefore support the hypothesis that in the cortico-cerebellar system, functionally related structures evolve in concert with each other. The evolutionary expansion of these prefrontal-projecting cerebellar territories might contribute to the evolution of the higher cognitive functions of humans. Copyright (c) 2009 Elsevier Inc. All rights reserved.

A brain imaging repository of normal structural MRI across the life course: Brain Images of Normal Subjects (BRAINS).

PubMed

Job, Dominic E; Dickie, David Alexander; Rodriguez, David; Robson, Andrew; Danso, Sammy; Pernet, Cyril; Bastin, Mark E; Boardman, James P; Murray, Alison D; Ahearn, Trevor; Waiter, Gordon D; Staff, Roger T; Deary, Ian J; Shenkin, Susan D; Wardlaw, Joanna M

2017-01-01

The Brain Images of Normal Subjects (BRAINS) Imagebank (http://www.brainsimagebank.ac.uk) is an integrated repository project hosted by the University of Edinburgh and sponsored by the Scottish Imaging Network: A Platform for Scientific Excellence (SINAPSE) collaborators. BRAINS provide sharing and archiving of detailed normal human brain imaging and relevant phenotypic data already collected in studies of healthy volunteers across the life-course. It particularly focusses on the extremes of age (currently older age, and in future perinatal) where variability is largest, and which are under-represented in existing databanks. BRAINS is a living imagebank where new data will be added when available. Currently BRAINS contains data from 808 healthy volunteers, from 15 to 81years of age, from 7 projects in 3 centres. Additional completed and ongoing studies of normal individuals from 1st to 10th decades are in preparation and will be included as they become available. BRAINS holds several MRI structural sequences, including T1, T2, T2* and fluid attenuated inversion recovery (FLAIR), available in DICOM (http://dicom.nema.org/); in future Diffusion Tensor Imaging (DTI) will be added where available. Images are linked to a wide range of 'textual data', such as age, medical history, physiological measures (e.g. blood pressure), medication use, cognitive ability, and perinatal information for pre/post-natal subjects. The imagebank can be searched to include or exclude ranges of these variables to create better estimates of 'what is normal' at different ages. Copyright © 2016 The Authors. Published by Elsevier Inc. All rights reserved.

Critical dynamics on a large human Open Connectome network

NASA Astrophysics Data System (ADS)

Ódor, Géza

2016-12-01

Extended numerical simulations of threshold models have been performed on a human brain network with N =836 733 connected nodes available from the Open Connectome Project. While in the case of simple threshold models a sharp discontinuous phase transition without any critical dynamics arises, variable threshold models exhibit extended power-law scaling regions. This is attributed to fact that Griffiths effects, stemming from the topological or interaction heterogeneity of the network, can become relevant if the input sensitivity of nodes is equalized. I have studied the effects of link directness, as well as the consequence of inhibitory connections. Nonuniversal power-law avalanche size and time distributions have been found with exponents agreeing with the values obtained in electrode experiments of the human brain. The dynamical critical region occurs in an extended control parameter space without the assumption of self-organized criticality.

Portable Wideband Microwave Imaging System for Intracranial Hemorrhage Detection Using Improved Back-projection Algorithm with Model of Effective Head Permittivity

PubMed Central

Mobashsher, Ahmed Toaha; Mahmoud, A.; Abbosh, A. M.

2016-01-01

Intracranial hemorrhage is a medical emergency that requires rapid detection and medication to restrict any brain damage to minimal. Here, an effective wideband microwave head imaging system for on-the-spot detection of intracranial hemorrhage is presented. The operation of the system relies on the dielectric contrast between healthy brain tissues and a hemorrhage that causes a strong microwave scattering. The system uses a compact sensing antenna, which has an ultra-wideband operation with directional radiation, and a portable, compact microwave transceiver for signal transmission and data acquisition. The collected data is processed to create a clear image of the brain using an improved back projection algorithm, which is based on a novel effective head permittivity model. The system is verified in realistic simulation and experimental environments using anatomically and electrically realistic human head phantoms. Quantitative and qualitative comparisons between the images from the proposed and existing algorithms demonstrate significant improvements in detection and localization accuracy. The radiation and thermal safety of the system are examined and verified. Initial human tests are conducted on healthy subjects with different head sizes. The reconstructed images are statistically analyzed and absence of false positive results indicate the efficacy of the proposed system in future preclinical trials. PMID:26842761

Portable Wideband Microwave Imaging System for Intracranial Hemorrhage Detection Using Improved Back-projection Algorithm with Model of Effective Head Permittivity

NASA Astrophysics Data System (ADS)

Mobashsher, Ahmed Toaha; Mahmoud, A.; Abbosh, A. M.

2016-02-01

Intracranial hemorrhage is a medical emergency that requires rapid detection and medication to restrict any brain damage to minimal. Here, an effective wideband microwave head imaging system for on-the-spot detection of intracranial hemorrhage is presented. The operation of the system relies on the dielectric contrast between healthy brain tissues and a hemorrhage that causes a strong microwave scattering. The system uses a compact sensing antenna, which has an ultra-wideband operation with directional radiation, and a portable, compact microwave transceiver for signal transmission and data acquisition. The collected data is processed to create a clear image of the brain using an improved back projection algorithm, which is based on a novel effective head permittivity model. The system is verified in realistic simulation and experimental environments using anatomically and electrically realistic human head phantoms. Quantitative and qualitative comparisons between the images from the proposed and existing algorithms demonstrate significant improvements in detection and localization accuracy. The radiation and thermal safety of the system are examined and verified. Initial human tests are conducted on healthy subjects with different head sizes. The reconstructed images are statistically analyzed and absence of false positive results indicate the efficacy of the proposed system in future preclinical trials.

Endocranial shape asymmetries in Pan paniscus, Pan troglodytes and Gorilla gorilla assessed via skull based landmark analysis.

PubMed

Balzeau, Antoine; Gilissen, Emmanuel

2010-07-01

Brain shape asymmetries or petalias consist of the extension of one cerebral hemisphere beyond the other. A larger frontal or caudal projection is usually coupled with a larger lateral extent of the more projecting hemisphere relative to the other. The concurrence of these petalial components is characteristic of hominins. Studies aimed at quantifying petalial asymmetries in human and great ape endocasts rely on the definition of the midline of the endocranial surface. Studies of brain material show that, at least in humans, most of the medial surface of the left occipital lobe distorts along the midline and protrudes on to the right side, making it difficult for midline and corresponding left and right reference point identification. In order to accurately quantify and compare brain shape asymmetries in extant hominid species, we propose here a new protocol based on the objective definition of cranial landmarks. We describe and quantify for the first time in three dimensions the positions of frontal and occipital protrusions in large samples of Pan paniscus, Pan troglodytes and Gorilla gorilla. This study confirms the existence of frontal and occipital petalias in African apes. Moreover, the detailed analysis of the 3D structure of these petalias reveals shared features, as well as features that are unique to the different great ape species.

Connectomic Insights into Topologically Centralized Network Edges and Relevant Motifs in the Human Brain

PubMed Central

Xia, Mingrui; Lin, Qixiang; Bi, Yanchao; He, Yong

2016-01-01

White matter (WM) tracts serve as important material substrates for information transfer across brain regions. However, the topological roles of WM tracts in global brain communications and their underlying microstructural basis remain poorly understood. Here, we employed diffusion magnetic resonance imaging and graph-theoretical approaches to identify the pivotal WM connections in human whole-brain networks and further investigated their wiring substrates (including WM microstructural organization and physical consumption) and topological contributions to the brain's network backbone. We found that the pivotal WM connections with highly topological-edge centrality were primarily distributed in several long-range cortico-cortical connections (including the corpus callosum, cingulum and inferior fronto-occipital fasciculus) and some projection tracts linking subcortical regions. These pivotal WM connections exhibited high levels of microstructural organization indicated by diffusion measures (the fractional anisotropy, the mean diffusivity and the axial diffusivity) and greater physical consumption indicated by streamline lengths, and contributed significantly to the brain's hubs and the rich-club structure. Network motif analysis further revealed their heavy participations in the organization of communication blocks, especially in routes involving inter-hemispheric heterotopic and extremely remote intra-hemispheric systems. Computational simulation models indicated the sharp decrease of global network integrity when attacking these highly centralized edges. Together, our results demonstrated high building-cost consumption and substantial communication capacity contributions for pivotal WM connections, which deepens our understanding of the topological mechanisms that govern the organization of human connectomes. PMID:27148015

Connectomic Insights into Topologically Centralized Network Edges and Relevant Motifs in the Human Brain.

PubMed

Xia, Mingrui; Lin, Qixiang; Bi, Yanchao; He, Yong

2016-01-01

White matter (WM) tracts serve as important material substrates for information transfer across brain regions. However, the topological roles of WM tracts in global brain communications and their underlying microstructural basis remain poorly understood. Here, we employed diffusion magnetic resonance imaging and graph-theoretical approaches to identify the pivotal WM connections in human whole-brain networks and further investigated their wiring substrates (including WM microstructural organization and physical consumption) and topological contributions to the brain's network backbone. We found that the pivotal WM connections with highly topological-edge centrality were primarily distributed in several long-range cortico-cortical connections (including the corpus callosum, cingulum and inferior fronto-occipital fasciculus) and some projection tracts linking subcortical regions. These pivotal WM connections exhibited high levels of microstructural organization indicated by diffusion measures (the fractional anisotropy, the mean diffusivity and the axial diffusivity) and greater physical consumption indicated by streamline lengths, and contributed significantly to the brain's hubs and the rich-club structure. Network motif analysis further revealed their heavy participations in the organization of communication blocks, especially in routes involving inter-hemispheric heterotopic and extremely remote intra-hemispheric systems. Computational simulation models indicated the sharp decrease of global network integrity when attacking these highly centralized edges. Together, our results demonstrated high building-cost consumption and substantial communication capacity contributions for pivotal WM connections, which deepens our understanding of the topological mechanisms that govern the organization of human connectomes.

77 FR 13578 - Disability and Rehabilitation Research Project; Traumatic Brain Injury Model Systems Centers

Federal Register 2010, 2011, 2012, 2013, 2014

2012-03-07

... DEPARTMENT OF EDUCATION Disability and Rehabilitation Research Project; Traumatic Brain Injury... Rehabilitation Research Project--Traumatic Brain Injury Model Systems Centers. CFDA Number: 84.133A-5. SUMMARY... for Disability and Rehabilitation Research Projects (DRRPs) to serve as Traumatic Brain Injury Model...

Intronic SNP in ESR1 encoding human estrogen receptor alpha is associated with brain ESR1 mRNA isoform expression and behavioral traits.

PubMed

Pinsonneault, Julia K; Frater, John T; Kompa, Benjamin; Mascarenhas, Roshan; Wang, Danxin; Sadee, Wolfgang

2017-01-01

Genetic variants of ESR1 have been implicated in multiple diseases, including behavioral disorders, but causative variants remain uncertain. We have searched for regulatory variants affecting ESR1 expression in human brain, measuring allelic ESR1 mRNA expression in human brain tissues with marker SNPs in exon4 representing ESR1-008 (or ESRα-36), and in the 3'UTR of ESR1-203, two main ESR1 isoforms in brain. In prefrontal cortex from subjects with bipolar disorder, schizophrenia, and controls (n = 35 each; Stanley Foundation brain bank), allelic ESR1 mRNA ratios deviated from unity up to tenfold at the exon4 marker SNP, with large allelic ratios observed primarily in bipolar and schizophrenic subjects. SNP scanning and targeted sequencing identified rs2144025, associated with large allelic mRNA ratios (p = 1.6E10-6). Moreover, rs2144025 was significantly associated with ESR1 mRNA levels in the Brain eQTL Almanac and in brain regions in the Genotype-Tissue Expression project. In four GWAS cohorts, rs2104425 was significantly associated with behavioral traits, including: hypomanic episodes in female bipolar disorder subjects (GAIN bipolar disorder study; p = 0.0004), comorbid psychological symptoms in both males and females with attention deficit hyperactivity disorder (GAIN ADHD, p = 0.00002), psychological diagnoses in female children (eMERGE study of childhood health, subject age ≥9, p = 0.0009), and traits in schizophrenia (e.g., grandiose delusions, GAIN schizophrenia, p = 0.0004). The first common ESR1 variant (MAF 12-33% across races) linked to regulatory functions, rs2144025 appears conditionally to affect ESR1 mRNA expression in the brain and modulate traits in behavioral disorders.

Intronic SNP in ESR1 encoding human estrogen receptor alpha is associated with brain ESR1 mRNA isoform expression and behavioral traits

PubMed Central

Kompa, Benjamin; Mascarenhas, Roshan; Wang, Danxin; Sadee, Wolfgang

2017-01-01

Genetic variants of ESR1 have been implicated in multiple diseases, including behavioral disorders, but causative variants remain uncertain. We have searched for regulatory variants affecting ESR1 expression in human brain, measuring allelic ESR1 mRNA expression in human brain tissues with marker SNPs in exon4 representing ESR1-008 (or ESRα-36), and in the 3’UTR of ESR1-203, two main ESR1 isoforms in brain. In prefrontal cortex from subjects with bipolar disorder, schizophrenia, and controls (n = 35 each; Stanley Foundation brain bank), allelic ESR1 mRNA ratios deviated from unity up to tenfold at the exon4 marker SNP, with large allelic ratios observed primarily in bipolar and schizophrenic subjects. SNP scanning and targeted sequencing identified rs2144025, associated with large allelic mRNA ratios (p = 1.6E10-6). Moreover, rs2144025 was significantly associated with ESR1 mRNA levels in the Brain eQTL Almanac and in brain regions in the Genotype-Tissue Expression project. In four GWAS cohorts, rs2104425 was significantly associated with behavioral traits, including: hypomanic episodes in female bipolar disorder subjects (GAIN bipolar disorder study; p = 0.0004), comorbid psychological symptoms in both males and females with attention deficit hyperactivity disorder (GAIN ADHD, p = 0.00002), psychological diagnoses in female children (eMERGE study of childhood health, subject age ≥9, p = 0.0009), and traits in schizophrenia (e.g., grandiose delusions, GAIN schizophrenia, p = 0.0004). The first common ESR1 variant (MAF 12–33% across races) linked to regulatory functions, rs2144025 appears conditionally to affect ESR1 mRNA expression in the brain and modulate traits in behavioral disorders. PMID:28617822

The von Economo neurons in fronto-insular and anterior cingulate cortex

PubMed Central

Allman, John M.; Tetreault, Nicole A.; Hakeem, Atiya Y.; Manaye, Kebreten F.; Semendeferi, Katerina; Erwin, Joseph M.; Park, Soyoung; Goubert, Virginie; Hof, Patrick R.

2011-01-01

The von Economo neurons (VENs) are large bipolar neurons located in fronto-insular cortex (FI) and anterior limbic area (LA) in great apes and humans but not in other primates. Our stereological counts of VENs in FI and LA show them to be more numerous in humans than in apes. In humans, small numbers of VENs appear the 36th week post conception, with numbers increasing during the first eight months after birth. There are significantly more VENs in the right hemisphere in postnatal brains; this may be related to asymmetries in the autonomic nervous system. VENs are also present in elephants and whales and may be a specialization related to very large brain size. The large size and simple dendritic structure of these projection neurons suggest that they rapidly send basic information from FI and LA to other parts of the brain, while slower neighboring pyramids send more detailed information. Selective destruction of VENs in early stages of fronto-temporal dementia implies that they are involved in empathy, social awareness, and self-control, consistent with evidence from functional imaging. PMID:21534993

The study of evolution and depression of the alpha-rhythm in the human brain EEG by means of wavelet-based methods

NASA Astrophysics Data System (ADS)

Runnova, A. E.; Zhuravlev, M. O.; Khramova, M. V.; Pysarchik, A. N.

2017-04-01

We study the appearance, development and depression of the alpha-rhythm in human EEG data during a psychophysiological experiment by stimulating cognitive activity with the perception of ambiguous object. The new method based on continuous wavelet transform allows to estimate the energy contribution of various components, including the alpha rhythm, in the general dynamics of the electrical activity of the projections of various areas of the brain. The decision-making process by observe ambiguous images is characterized by specific oscillatory alfa-rhytm patterns in the multi-channel EEG data. We have shown the repeatability of detected principles of the alpha-rhythm evolution in a data of group of 12 healthy male volunteers.

Task-Related Edge Density (TED)—A New Method for Revealing Dynamic Network Formation in fMRI Data of the Human Brain

PubMed Central

Lohmann, Gabriele; Stelzer, Johannes; Zuber, Verena; Buschmann, Tilo; Margulies, Daniel; Bartels, Andreas; Scheffler, Klaus

2016-01-01

The formation of transient networks in response to external stimuli or as a reflection of internal cognitive processes is a hallmark of human brain function. However, its identification in fMRI data of the human brain is notoriously difficult. Here we propose a new method of fMRI data analysis that tackles this problem by considering large-scale, task-related synchronisation networks. Networks consist of nodes and edges connecting them, where nodes correspond to voxels in fMRI data, and the weight of an edge is determined via task-related changes in dynamic synchronisation between their respective times series. Based on these definitions, we developed a new data analysis algorithm that identifies edges that show differing levels of synchrony between two distinct task conditions and that occur in dense packs with similar characteristics. Hence, we call this approach “Task-related Edge Density” (TED). TED proved to be a very strong marker for dynamic network formation that easily lends itself to statistical analysis using large scale statistical inference. A major advantage of TED compared to other methods is that it does not depend on any specific hemodynamic response model, and it also does not require a presegmentation of the data for dimensionality reduction as it can handle large networks consisting of tens of thousands of voxels. We applied TED to fMRI data of a fingertapping and an emotion processing task provided by the Human Connectome Project. TED revealed network-based involvement of a large number of brain areas that evaded detection using traditional GLM-based analysis. We show that our proposed method provides an entirely new window into the immense complexity of human brain function. PMID:27341204

Task-Related Edge Density (TED)-A New Method for Revealing Dynamic Network Formation in fMRI Data of the Human Brain.

PubMed

Lohmann, Gabriele; Stelzer, Johannes; Zuber, Verena; Buschmann, Tilo; Margulies, Daniel; Bartels, Andreas; Scheffler, Klaus

2016-01-01

The formation of transient networks in response to external stimuli or as a reflection of internal cognitive processes is a hallmark of human brain function. However, its identification in fMRI data of the human brain is notoriously difficult. Here we propose a new method of fMRI data analysis that tackles this problem by considering large-scale, task-related synchronisation networks. Networks consist of nodes and edges connecting them, where nodes correspond to voxels in fMRI data, and the weight of an edge is determined via task-related changes in dynamic synchronisation between their respective times series. Based on these definitions, we developed a new data analysis algorithm that identifies edges that show differing levels of synchrony between two distinct task conditions and that occur in dense packs with similar characteristics. Hence, we call this approach "Task-related Edge Density" (TED). TED proved to be a very strong marker for dynamic network formation that easily lends itself to statistical analysis using large scale statistical inference. A major advantage of TED compared to other methods is that it does not depend on any specific hemodynamic response model, and it also does not require a presegmentation of the data for dimensionality reduction as it can handle large networks consisting of tens of thousands of voxels. We applied TED to fMRI data of a fingertapping and an emotion processing task provided by the Human Connectome Project. TED revealed network-based involvement of a large number of brain areas that evaded detection using traditional GLM-based analysis. We show that our proposed method provides an entirely new window into the immense complexity of human brain function.

Lentiviral infection of rhesus macaques causes long-term injury to cortical and hippocampal projections of prostaglandin-expressing cholinergic basal forebrain neurons.

PubMed

Depboylu, Candan; Weihe, Eberhard; Eiden, Lee E

2012-01-01

The simian immunodeficiency virus (SIV) macaque model resembles human immunodeficiency virus-acquired immunodeficiency syndrome (AIDS) and associated brain dysfunction. Altered expression of synaptic markers and transmitters in neuro-AIDS has been reported, but limited data exist for the cholinergic system and lipid mediators such as prostaglandins. Here, we analyzed cholinergic basal forebrain neurons with their telencephalic projections and the rate-limiting enzymes for prostaglandin synthesis, cyclooxygenase isotypes 1 and 2 (COX1 and COX2) in the brains of SIV-infected macaques with or without encephalitis and antiretroviral therapy and uninfected controls.Cyclooxygenase isotype 1, but not COX2, was coexpressed with markers of cholinergic phenotype, that is, choline acetyltransferase and vesicular acetylcholine transporter (VAChT), in basal forebrain neurons of monkey, as well as human, brain. Cyclooxygenase isotype 1 was decreased in basal forebrain neurons in macaques with AIDS versus uninfected and asymptomatic SIV-infected macaques. The VAChT-positive fiber density was reduced in frontal, parietal, and hippocampal-entorhinal cortex. Although brain SIV burden and associated COX1- and COX2-positive mononuclear and endothelial inflammatory reactions were mostly reversed in AIDS-diseased macaques that received 6-chloro-2',3'-dideoxyguanosine treatment, decreased VAChT-positive terminal density and reduced cholinergic COX1 expression were not. Thus, COX1 expression is a feature of primate cholinergic basal forebrain neurons; it may be functionally important and a critical biomarker of cholinergic dysregulation accompanying lentiviral encephalopathy. These results further imply that insufficiently prompt initiation of antiretroviral therapy in lentiviral infection may lead to neurostructurally unremarkable but neurochemically prominent irreversible brain damage.

Synthesis of three novel fluorine-18 labeled analogues of L-deprenyl for positron emission tomography (PET) studies of monoamine oxidase B (MAO-B).

PubMed

Nag, Sangram; Lehmann, Lutz; Heinrich, Tobias; Thiele, Andrea; Kettschau, Georg; Nakao, Ryuji; Gulyás, Balázs; Halldin, Christer

2011-10-27

The aim in this project was to synthesize and to study fluorine-18 labeled analogues of l-deprenyl which bind selectively to the enzyme monoamine oxidase B (MAO-B). Three fluorinated l-deprenyl analogues have been generated in multistep organic syntheses. The most promising fluorine-18 compound N-[(2S)-1-[(18)F]fluoro-3-phenylpropan-2-yl]-N-methylprop-2-yn-1-amine (4c) was synthesized by a one-step fluorine-18 nucleophilic substitution reaction. Autoradiography on human brain tissue sections demonstrated specific binding for compound 4c to brain regions known to have a high content of MAO-B. In addition, the corresponding nonradioactive fluorine-19 compound (13) inhibited recombinant human MAO-B with an IC(50) of 170.5 ± 29 nM but did not inhibit recombinant human MAO-A (IC(50) > 2000 nM), demonstrating its specificity. Biodistribution of 4c in mice showed high initial brain uptake leveling at 5.2 ± 0.04%ID/g after 2 min post injection. In conclusion, compound 4c is a specific inhibitor of MAO-B with high initial brain uptake in mice and is, therefore, a candidate for further investigation in PET.

Effect of alcohol use disorder on oxytocin peptide and receptor mRNA expression in human brain: A post-mortem case-control study.

PubMed

Lee, Mary R; Schwandt, Melanie L; Sankar, Vignesh; Suchankova, Petra; Sun, Hui; Leggio, Lorenzo

2017-11-01

Animal and human evidence supports a role for oxytocin in alcohol-seeking behaviors. There is interest, therefore, in targeting the oxytocin pathway as a new pharmacologic approach to treat alcohol use disorder. To this end, it is important to understand the effect of alcohol use disorder on endogenous oxytocin in brain regions that are relevant for the initiation and maintenance of alcohol use disorder. We examined human post-mortem brain tissue from males with alcohol use disorder (n=11) compared to nonalcohol dependent male controls (n=16). We a priori targeted five brain regions that in rodent studies, are projection areas for oxytocin neurons: nucleus accumbens, amygdala, hippocampus, ventral tegmental area and prefrontal cortex. Fold change in mRNA levels of oxytocin peptide and receptor were measured in each of the brain regions studied. Fold change for oxytocin peptide mRNA was significantly elevated in the prefrontal cortex of subjects with alcohol use disorder compared to controls (uncorrected p=0.0001; FDR-corrected p=0.001). For the entire sample of 27 subjects, there was a significant positive correlation between the fold change in oxytocin peptide mRNA in the prefrontal cortex and both daily alcohol intake (r 2 =0.38; p=0.002) and drinks per week (r 2 =0.24; p=0.02). Results are discussed in light of the previous animal and human literature on changes in the endogenous oxytocin system as an effect of chronic alcohol exposure. Copyright © 2017. Published by Elsevier Ltd.

Technical advances power neuroscience

DOE Office of Scientific and Technical Information (OSTI.GOV)

Barinaga, M.

New techniques are helping researchers study the development of nerve cells in cell cultures and in vivo. These new methods are offering insights into the brain that were not available even a couple of years ago. Among the new advances discussed are imaging technology for evaluating the thinking human brain. One area in which researchers have made recent progress is the quest for ways to create immortal cell lines from specific types of nerve cells. Other projects using genetically engineered retroviruses and tumor-inducing genes, as well as gene regulation are discussed. Recent advances in neuroscience techniques apply not only tomore » neurons, but also to whole brains as well. One example is a high-resulution electroencephalogram (EEG). Although the EEG cannot pin down the actual sites of activity as precisely as static brain imaging methods, it complements them with real-time recording that can keep up with the very rapid pace of brain activity.« less

Large scale digital atlases in neuroscience

NASA Astrophysics Data System (ADS)

Hawrylycz, M.; Feng, D.; Lau, C.; Kuan, C.; Miller, J.; Dang, C.; Ng, L.

2014-03-01

Imaging in neuroscience has revolutionized our current understanding of brain structure, architecture and increasingly its function. Many characteristics of morphology, cell type, and neuronal circuitry have been elucidated through methods of neuroimaging. Combining this data in a meaningful, standardized, and accessible manner is the scope and goal of the digital brain atlas. Digital brain atlases are used today in neuroscience to characterize the spatial organization of neuronal structures, for planning and guidance during neurosurgery, and as a reference for interpreting other data modalities such as gene expression and connectivity data. The field of digital atlases is extensive and in addition to atlases of the human includes high quality brain atlases of the mouse, rat, rhesus macaque, and other model organisms. Using techniques based on histology, structural and functional magnetic resonance imaging as well as gene expression data, modern digital atlases use probabilistic and multimodal techniques, as well as sophisticated visualization software to form an integrated product. Toward this goal, brain atlases form a common coordinate framework for summarizing, accessing, and organizing this knowledge and will undoubtedly remain a key technology in neuroscience in the future. Since the development of its flagship project of a genome wide image-based atlas of the mouse brain, the Allen Institute for Brain Science has used imaging as a primary data modality for many of its large scale atlas projects. We present an overview of Allen Institute digital atlases in neuroscience, with a focus on the challenges and opportunities for image processing and computation.

Neuroanatomical prerequisites for language functions in the maturing brain.

PubMed

Brauer, Jens; Anwander, Alfred; Friederici, Angela D

2011-02-01

The 2 major language-relevant cortical regions in the human brain, Broca's area and Wernicke's area, are connected via the fibers of the arcuate fasciculus/superior longitudinal fasciculus (AF/SLF). Here, we compared this pathway in adults and children and its relation to language processing during development. Comparison of fiber properties demonstrated lower anisotropy in children's AF/SLF, arguing for an immature status of this particular pathway with conceivably a lower degree of myelination. Combined diffusion tensor imaging (DTI) data and functional magnetic resonance imaging (fMRI) data indicated that in adults the termination of the AF/SLF fiber projection is compatible with functional activation in Broca's area, that is pars opercularis. In children, activation in Broca's area extended from the pars opercularis into the pars triangularis revealing an alternative connection to the temporal lobe (Wernicke's area) via the ventrally projecting extreme capsule fiber system. fMRI and DTI data converge to indicate that adults make use of a more confined language network than children based on ongoing maturation of the structural network. Our data suggest relations between language development and brain maturation and, moreover, indicate the brain's plasticity to adjust its function to available structural prerequisites.

Human FGF1 promoter is active in ependymal cells and dopaminergic neurons in the brains of F1B-GFP transgenic mice.

PubMed

Chen, Mei-Shu; Lin, Hua-Kuo; Chiu, Hsun; Lee, Don-Ching; Chung, Yu-Fen; Chiu, Ing-Ming

2015-03-01

FGF1 is involved in multiple biological functions and exhibits the importance in neuroprotective effects. Our previous studies indicated that, in human brain and retina, the FGF1B promoter controlled the expression of FGF1. However, the exact function and regulation of FGF1 in brain is still unclear. Here, we generated F1B-GFP transgenic mice that expressed the GFP reporter gene under the control of human FGF1B promoter (-540 to +31). Using the fresh brain sections of F1B-GFP transgenic mice, we found that the F1B-GFP cells expressed strong fluorescent signals in the ventricular system throughout the brain. The results of immunohistochemistry further showed that two distinct populations of F1B-GFP(+) cells existed in the brains of F1B-GFP transgenic mice. We demonstrated that one population of F1B-GFP(+) cells was ependymal cells, which distributed along the entire ventricles, and the second population of F1B-GFP(+) cells was neuronal cells that projected their long processes into multiple directions in specific areas of the brain. The double labeling of F1B-GFP(+) cells and tyrosine hydroxylase indicated that a subpopulation of F1B-GFP(+) -neuronal cells was dopaminergic neurons. Importantly, these F1B-GFP(+) /TH(+) cells were distributed in the main dopaminergic neuronal groups including hypothalamus, ventral tegmental area, and raphe nuclei. These results suggested that human FGF1B promoter was active in ependymal cells, neurons, and a portion of dopaminergic neurons. Thus, the F1B-GFP transgenic mice provide an animal model not only for studying FGF1 gene expression in vivo but also for understanding the role of FGF1 contribution in neurodegenerative disorders such as Parkinson's disease and Alzheimer's disease. © 2014 The Authors Developmental Neurobiology Published by Wiley Periodicals, Inc.

Convergence of Cortical, Thalamocortical, and Callosal Pathways during Human Fetal Development Revealed by Diffusion MRI Tractography.

PubMed

Wang, Rongpin; Wilkinson, Molly; Kane, Tara; Takahashi, Emi

2017-01-01

There has been evidence that during brain development, emerging thalamocortical (TC) and corticothalamic (CT) pathways converge in some brain regions and follow each other's trajectories to their final destinations. Corpus callosal (CC) pathways also emerge at a similar developmental stage, and are known to converge with TC pathways in specific cortical regions in mature brains. Given the functional relationships between TC and CC pathways, anatomical convergence of the two pathways are likely important for their functional integration. However, it is unknown (1) where TC and CT subcortically converge in the human brain, and (2) where TC and CC converge in the cortex of the human brain, due to the limitations of non-invasive methods. The goals of this study were to describe the spatio-temporal relationships in the development of the TC/CT and CC pathways in the human brain, using high-angular resolution diffusion MR imaging (HARDI) tractography. Emerging cortical, TC and CC pathways were identified in postmortem fetal brains ranging from 17 gestational weeks (GW) to 30 GW, as well as in vivo 34-40 GW newborns. Some pathways from the thalami were found to be converged with pathways from the cerebral cortex as early as 17 GW. Such convergence was observed mainly in anterior and middle regions of the brain until 21 GW. At 22 GW and onwards, posterior pathways from the thalami also converged with cortical pathways. Many CC pathways reached the full length up to the cortical surface as early as 17 GW, while pathways linked to thalami (not only TC axons but also including pathways linked to thalamic neuronal migration) reached the cortical surface at and after 20 GW. These results suggest that CC pathways developed earlier than the TC pathways. The two pathways were widespread at early stages, but by 40 GW they condensed and formed groups of pathways that projected to specific regions of the cortex and overlapped in some brain regions. These results suggest that HARDI tractography has the potential to identify developing TC/CT and CC pathways with the timing and location of their convergence in fetal stages persisting in postnatal development.

Convergence of Cortical, Thalamocortical, and Callosal Pathways during Human Fetal Development Revealed by Diffusion MRI Tractography

PubMed Central

Wang, Rongpin; Wilkinson, Molly; Kane, Tara; Takahashi, Emi

2017-01-01

There has been evidence that during brain development, emerging thalamocortical (TC) and corticothalamic (CT) pathways converge in some brain regions and follow each other's trajectories to their final destinations. Corpus callosal (CC) pathways also emerge at a similar developmental stage, and are known to converge with TC pathways in specific cortical regions in mature brains. Given the functional relationships between TC and CC pathways, anatomical convergence of the two pathways are likely important for their functional integration. However, it is unknown (1) where TC and CT subcortically converge in the human brain, and (2) where TC and CC converge in the cortex of the human brain, due to the limitations of non-invasive methods. The goals of this study were to describe the spatio-temporal relationships in the development of the TC/CT and CC pathways in the human brain, using high-angular resolution diffusion MR imaging (HARDI) tractography. Emerging cortical, TC and CC pathways were identified in postmortem fetal brains ranging from 17 gestational weeks (GW) to 30 GW, as well as in vivo 34–40 GW newborns. Some pathways from the thalami were found to be converged with pathways from the cerebral cortex as early as 17 GW. Such convergence was observed mainly in anterior and middle regions of the brain until 21 GW. At 22 GW and onwards, posterior pathways from the thalami also converged with cortical pathways. Many CC pathways reached the full length up to the cortical surface as early as 17 GW, while pathways linked to thalami (not only TC axons but also including pathways linked to thalamic neuronal migration) reached the cortical surface at and after 20 GW. These results suggest that CC pathways developed earlier than the TC pathways. The two pathways were widespread at early stages, but by 40 GW they condensed and formed groups of pathways that projected to specific regions of the cortex and overlapped in some brain regions. These results suggest that HARDI tractography has the potential to identify developing TC/CT and CC pathways with the timing and location of their convergence in fetal stages persisting in postnatal development. PMID:29163000

Lentiviral Infection of Rhesus Macaques Causes Long-Term Injury to Cortical and Hippocampal Projections of Prostaglandin-Expressing Cholinergic Basal Forebrain Neurons

PubMed Central

Depboylu, Candan; Weihe, Eberhard; Eiden, Lee E.

2011-01-01

The simian immunodeficiency virus (SIV) macaque model resembles human HIV-AIDS and associated brain dysfunction. Altered expression of synaptic markers and transmitters in neuro-AIDS has been reported, but limited data exist for the cholinergic system and lipid mediators such as prostaglandins. Here, we analyzed cholinergic basal forebrain neurons with their telencephalic projections and the rate-limiting enzymes for prostaglandin synthesis, cyclooxygenases 1 and 2 (COX1 and 2) in brains of SIV-infected macaques with and without encephalitis and antiretroviral therapy, and uninfected controls. COX1 but not COX2 was co-expressed with markers of cholinergic phenotype, i.e. choline acetyltransferase and vesicular acetylcholine transporter (VAChT), in basal forebrain neurons of monkey, as well as human samples. COX1 was decreased in basal forebrain neurons in macaques with AIDS vs. uninfected and asymptomatic SIV-infected macaques. VAChT-positive fiber density was reduced in frontal, parietal and hippocampal-entorhinal cortex. Although brain SIV burden and associated COX1- and COX2-positive mononuclear and endothelial inflammatory reactions were mostly reversed in AIDS-diseased macaques that received 6-chloro-2′,3′-dideoxyguanosine treatment, decreased VAChT-positive terminal density and reduced cholinergic COX1 expression were not. Thus, COX1 expression is a feature of primate cholinergic basal forebrain neurons; it may be functionally important and a critical biomarker of cholinergic dysregulation accompanying lentiviral encephalopathy. These results imply that insufficiently prompt initiation of antiretroviral therapy in lentiviral infection may lead to neurostructurally unremarkable but neurochemically prominent, irreversible brain damage. PMID:22157616

Multivariate Heteroscedasticity Models for Functional Brain Connectivity.

PubMed

Seiler, Christof; Holmes, Susan

2017-01-01

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

Investigating the Intersession Reliability of Dynamic Brain-State Properties.

PubMed

Smith, Derek M; Zhao, Yrian; Keilholz, Shella D; Schumacher, Eric H

2018-06-01

Dynamic functional connectivity metrics have much to offer to the neuroscience of individual differences of cognition. Yet, despite the recent expansion in dynamic connectivity research, limited resources have been devoted to the study of the reliability of these connectivity measures. To address this, resting-state functional magnetic resonance imaging data from 100 Human Connectome Project subjects were compared across 2 scan days. Brain states (i.e., patterns of coactivity across regions) were identified by classifying each time frame using k means clustering. This was done with and without global signal regression (GSR). Multiple gauges of reliability indicated consistency in the brain-state properties across days and GSR attenuated the reliability of the brain states. Changes in the brain-state properties across the course of the scan were investigated as well. The results demonstrate that summary metrics describing the clustering of individual time frames have adequate test/retest reliability, and thus, these patterns of brain activation may hold promise for individual-difference research.

Specific PET Imaging Probes for Early Detection of Prostate Cancer Metastases

DTIC Science & Technology

2011-05-01

K. S. (2005) 67-kDa laminin receptor promotes internalization of cytotoxic necrotizing factor 1-expressing Escherichia coli K1 into human brain...Chung JW, Kim KS (2005) 67-kDa laminin receptor promotes internalization of cytotoxic necrotizing factor 1-expressing Esch- erichia coli K1 into human...SUBTITLE 5a. CONTRACT NUMBER 5b. GRANT NUMBER 5c. PROGRAM ELEMENT NUMBER 6. AUTHOR(S) 5d. PROJECT NUMBER 5e. TASK NUMBER E -Mail: 5f

Functional connectomics from resting-state fMRI

PubMed Central

Smith, Stephen M; Vidaurre, Diego; Beckmann, Christian F; Glasser, Matthew F; Jenkinson, Mark; Miller, Karla L; Nichols, Thomas E; Robinson, Emma; Salimi-Khorshidi, Gholamreza; Woolrich, Mark W; Barch, Deanna M; Uğurbil, Kamil; Van Essen, David C

2014-01-01

Spontaneous fluctuations in activity in different parts of the brain can be used to study functional brain networks. We review the use of resting-state functional MRI for the purpose of mapping the macroscopic functional connectome. After describing MRI acquisition and image processing methods commonly used to generate data in a form amenable to connectomics network analysis, we discuss different approaches for estimating network structure from that data. Finally, we describe new possibilities resulting from the high-quality rfMRI data being generated by the Human Connectome Project, and highlight some upcoming challenges in functional connectomics. PMID:24238796

Homo sapiens-Specific Binding Site Variants within Brain Exclusive Enhancers Are Subject to Accelerated Divergence across Human Population.

PubMed

Zehra, Rabail; Abbasi, Amir Ali

2018-03-01

Empirical assessments of human accelerated noncoding DNA frgaments have delineated presence of many cis-regulatory elements. Enhancers make up an important category of such accelerated cis-regulatory elements that efficiently control the spatiotemporal expression of many developmental genes. Establishing plausible reasons for accelerated enhancer sequence divergence in Homo sapiens has been termed significant in various previously published studies. This acceleration by including closely related primates and archaic human data has the potential to open up evolutionary avenues for deducing present-day brain structure. This study relied on empirically confirmed brain exclusive enhancers to avoid any misjudgments about their regulatory status and categorized among them a subset of enhancers with an exceptionally accelerated rate of lineage specific divergence in humans. In this assorted set, 13 distinct transcription factor binding sites were located that possessed unique existence in humans. Three of 13 such sites belonging to transcription factors SOX2, RUNX1/3, and FOS/JUND possessed single nucleotide variants that made them unique to H. sapiens upon comparisons with Neandertal and Denisovan orthologous sequences. These variants modifying the binding sites in modern human lineage were further substantiated as single nucleotide polymorphisms via exploiting 1000 Genomes Project Phase3 data. Long range haplotype based tests laid out evidence of positive selection to be governing in African population on two of the modern human motif modifying alleles with strongest results for SOX2 binding site. In sum, our study acknowledges acceleration in noncoding regulatory landscape of the genome and highlights functional parts within it to have undergone accelerated divergence in present-day human population.

Neurophysiological Basis of Multi-Scale Entropy of Brain Complexity and Its Relationship With Functional Connectivity.

PubMed

Wang, Danny J J; Jann, Kay; Fan, Chang; Qiao, Yang; Zang, Yu-Feng; Lu, Hanbing; Yang, Yihong

2018-01-01

Recently, non-linear statistical measures such as multi-scale entropy (MSE) have been introduced as indices of the complexity of electrophysiology and fMRI time-series across multiple time scales. In this work, we investigated the neurophysiological underpinnings of complexity (MSE) of electrophysiology and fMRI signals and their relations to functional connectivity (FC). MSE and FC analyses were performed on simulated data using neural mass model based brain network model with the Brain Dynamics Toolbox, on animal models with concurrent recording of fMRI and electrophysiology in conjunction with pharmacological manipulations, and on resting-state fMRI data from the Human Connectome Project. Our results show that the complexity of regional electrophysiology and fMRI signals is positively correlated with network FC. The associations between MSE and FC are dependent on the temporal scales or frequencies, with higher associations between MSE and FC at lower temporal frequencies. Our results from theoretical modeling, animal experiment and human fMRI indicate that (1) Regional neural complexity and network FC may be two related aspects of brain's information processing: the more complex regional neural activity, the higher FC this region has with other brain regions; (2) MSE at high and low frequencies may represent local and distributed information processing across brain regions. Based on literature and our data, we propose that the complexity of regional neural signals may serve as an index of the brain's capacity of information processing-increased complexity may indicate greater transition or exploration between different states of brain networks, thereby a greater propensity for information processing.

A common brain network among state, trait, and pathological anxiety from whole-brain functional connectivity.

PubMed

Takagi, Yu; Sakai, Yuki; Abe, Yoshinari; Nishida, Seiji; Harrison, Ben J; Martínez-Zalacaín, Ignacio; Soriano-Mas, Carles; Narumoto, Jin; Tanaka, Saori C

2018-05-15

Anxiety is one of the most common mental states of humans. Although it drives us to avoid frightening situations and to achieve our goals, it may also impose significant suffering and burden if it becomes extreme. Because we experience anxiety in a variety of forms, previous studies investigated neural substrates of anxiety in a variety of ways. These studies revealed that individuals with high state, trait, or pathological anxiety showed altered neural substrates. However, no studies have directly investigated whether the different dimensions of anxiety share a common neural substrate, despite its theoretical and practical importance. Here, we investigated a brain network of anxiety shared by different dimensions of anxiety in a unified analytical framework using functional magnetic resonance imaging (fMRI). We analyzed different datasets in a single scale, which was defined by an anxiety-related brain network derived from whole brain. We first conducted the anxiety provocation task with healthy participants who tended to feel anxiety related to obsessive-compulsive disorder (OCD) in their daily life. We found a common state anxiety brain network across participants (1585 trials obtained from 10 participants). Then, using the resting-state fMRI in combination with the participants' behavioral trait anxiety scale scores (879 participants from the Human Connectome Project), we demonstrated that trait anxiety shared the same brain network as state anxiety. Furthermore, the brain network between common to state and trait anxiety could detect patients with OCD, which is characterized by pathological anxiety-driven behaviors (174 participants from multi-site datasets). Our findings provide direct evidence that different dimensions of anxiety have a substantial biological inter-relationship. Our results also provide a biologically defined dimension of anxiety, which may promote further investigation of various human characteristics, including psychiatric disorders, from the perspective of anxiety. Copyright © 2018 The Authors. Published by Elsevier Inc. All rights reserved.

Teacher education professionals as partners in health science outreach.

PubMed

Houtz, Lynne E; Kosoko-Lasaki, Omofolasade; Zardetto-Smith, Andrea M; Mu, Keli; Royeen, Charlotte B

2004-01-01

Medical school and other health science outreach programs to educate and recruit precollege students always have relied on successful collaborative efforts. Creighton University shares the value, significance, and strategies of involving teacher education professionals in several of its current outreach programs, including HPPI, Brains Rule! Neuroscience Expositions, and HHMI Build a Human Project. The education department partner serves as an essential team member in the development, implementation, assessment, and dissemination of these projects to promote science and mathematics achievement and interest in medical careers. Specific examples and mistakes to avoid are included.

Graph Theoretical Analysis Reveals: Women's Brains Are Better Connected than Men's.

PubMed

Szalkai, Balázs; Varga, Bálint; Grolmusz, Vince

2015-01-01

Deep graph-theoretic ideas in the context with the graph of the World Wide Web led to the definition of Google's PageRank and the subsequent rise of the most popular search engine to date. Brain graphs, or connectomes, are being widely explored today. We believe that non-trivial graph theoretic concepts, similarly as it happened in the case of the World Wide Web, will lead to discoveries enlightening the structural and also the functional details of the animal and human brains. When scientists examine large networks of tens or hundreds of millions of vertices, only fast algorithms can be applied because of the size constraints. In the case of diffusion MRI-based structural human brain imaging, the effective vertex number of the connectomes, or brain graphs derived from the data is on the scale of several hundred today. That size facilitates applying strict mathematical graph algorithms even for some hard-to-compute (or NP-hard) quantities like vertex cover or balanced minimum cut. In the present work we have examined brain graphs, computed from the data of the Human Connectome Project, recorded from male and female subjects between ages 22 and 35. Significant differences were found between the male and female structural brain graphs: we show that the average female connectome has more edges, is a better expander graph, has larger minimal bisection width, and has more spanning trees than the average male connectome. Since the average female brain weighs less than the brain of males, these properties show that the female brain has better graph theoretical properties, in a sense, than the brain of males. It is known that the female brain has a smaller gray matter/white matter ratio than males, that is, a larger white matter/gray matter ratio than the brain of males; this observation is in line with our findings concerning the number of edges, since the white matter consists of myelinated axons, which, in turn, roughly correspond to the connections in the brain graph. We have also found that the minimum bisection width, normalized with the edge number, is also significantly larger in the right and the left hemispheres in females: therefore, the differing bisection widths are independent from the difference in the number of edges.

Graph Theoretical Analysis Reveals: Women’s Brains Are Better Connected than Men’s

PubMed Central

Szalkai, Balázs; Varga, Bálint; Grolmusz, Vince

2015-01-01

Deep graph-theoretic ideas in the context with the graph of the World Wide Web led to the definition of Google’s PageRank and the subsequent rise of the most popular search engine to date. Brain graphs, or connectomes, are being widely explored today. We believe that non-trivial graph theoretic concepts, similarly as it happened in the case of the World Wide Web, will lead to discoveries enlightening the structural and also the functional details of the animal and human brains. When scientists examine large networks of tens or hundreds of millions of vertices, only fast algorithms can be applied because of the size constraints. In the case of diffusion MRI-based structural human brain imaging, the effective vertex number of the connectomes, or brain graphs derived from the data is on the scale of several hundred today. That size facilitates applying strict mathematical graph algorithms even for some hard-to-compute (or NP-hard) quantities like vertex cover or balanced minimum cut. In the present work we have examined brain graphs, computed from the data of the Human Connectome Project, recorded from male and female subjects between ages 22 and 35. Significant differences were found between the male and female structural brain graphs: we show that the average female connectome has more edges, is a better expander graph, has larger minimal bisection width, and has more spanning trees than the average male connectome. Since the average female brain weighs less than the brain of males, these properties show that the female brain has better graph theoretical properties, in a sense, than the brain of males. It is known that the female brain has a smaller gray matter/white matter ratio than males, that is, a larger white matter/gray matter ratio than the brain of males; this observation is in line with our findings concerning the number of edges, since the white matter consists of myelinated axons, which, in turn, roughly correspond to the connections in the brain graph. We have also found that the minimum bisection width, normalized with the edge number, is also significantly larger in the right and the left hemispheres in females: therefore, the differing bisection widths are independent from the difference in the number of edges. PMID:26132764

Human brain mapping: A systematic comparison of parcellation methods for the human cerebral cortex.

PubMed

Arslan, Salim; Ktena, Sofia Ira; Makropoulos, Antonios; Robinson, Emma C; Rueckert, Daniel; Parisot, Sarah

2018-04-15

The macro-connectome elucidates the pathways through which brain regions are structurally connected or functionally coupled to perform a specific cognitive task. It embodies the notion of representing and understanding all connections within the brain as a network, while the subdivision of the brain into interacting functional units is inherent in its architecture. As a result, the definition of network nodes is one of the most critical steps in connectivity network analysis. Although brain atlases obtained from cytoarchitecture or anatomy have long been used for this task, connectivity-driven methods have arisen only recently, aiming to delineate more homogeneous and functionally coherent regions. This study provides a systematic comparison between anatomical, connectivity-driven and random parcellation methods proposed in the thriving field of brain parcellation. Using resting-state functional MRI data from the Human Connectome Project and a plethora of quantitative evaluation techniques investigated in the literature, we evaluate 10 subject-level and 24 groupwise parcellation methods at different resolutions. We assess the accuracy of parcellations from four different aspects: (1) reproducibility across different acquisitions and groups, (2) fidelity to the underlying connectivity data, (3) agreement with fMRI task activation, myelin maps, and cytoarchitectural areas, and (4) network analysis. This extensive evaluation of different parcellations generated at the subject and group level highlights the strengths and shortcomings of the various methods and aims to provide a guideline for the choice of parcellation technique and resolution according to the task at hand. The results obtained in this study suggest that there is no optimal method able to address all the challenges faced in this endeavour simultaneously. Copyright © 2017 Elsevier Inc. All rights reserved.

China Brain Project: Basic Neuroscience, Brain Diseases, and Brain-Inspired Computing.

PubMed

Poo, Mu-Ming; Du, Jiu-Lin; Ip, Nancy Y; Xiong, Zhi-Qi; Xu, Bo; Tan, Tieniu

2016-11-02

The China Brain Project covers both basic research on neural mechanisms underlying cognition and translational research for the diagnosis and intervention of brain diseases as well as for brain-inspired intelligence technology. We discuss some emerging themes, with emphasis on unique aspects. Copyright © 2016. Published by Elsevier Inc.

All the Vice Chancellor's Neuroscientists: Unity to Achieve Success in Solving Malaysia's Diseases via Upgrading Clinical Services and Neuroscience Research.

PubMed

Abdullah, Jafri Malin

2013-05-01

President Obama of the United States of America announced this April the Brain Research Through Advancing Innovative Neurotechnologies (BRAIN for short) investment, while Professor Henry Markram's team based in the European Union will spend over a billion euros on the Human Brain Project, breaking through the unknowns in the fifth science of the decade: Neuroscience. Malaysia's growth in the same field needs to be augmented, and thus the Universiti Sains Malaysia's vision is to excel in the field of clinical brain sciences, mind sciences and neurosciences. This will naturally bring up the level of research in the country simultaneously. Thus, a center was recently established to coordinate this venture. The four-year Integrated Neuroscience Program established recently will be a sustainable source of neuroscientists for the country. We hope to establish ourselves by 2020 as a global university with neurosciences research as an important flagship.

Embedded sparse representation of fMRI data via group-wise dictionary optimization

NASA Astrophysics Data System (ADS)

Zhu, Dajiang; Lin, Binbin; Faskowitz, Joshua; Ye, Jieping; Thompson, Paul M.

2016-03-01

Sparse learning enables dimension reduction and efficient modeling of high dimensional signals and images, but it may need to be tailored to best suit specific applications and datasets. Here we used sparse learning to efficiently represent functional magnetic resonance imaging (fMRI) data from the human brain. We propose a novel embedded sparse representation (ESR), to identify the most consistent dictionary atoms across different brain datasets via an iterative group-wise dictionary optimization procedure. In this framework, we introduced additional criteria to make the learned dictionary atoms more consistent across different subjects. We successfully identified four common dictionary atoms that follow the external task stimuli with very high accuracy. After projecting the corresponding coefficient vectors back into the 3-D brain volume space, the spatial patterns are also consistent with traditional fMRI analysis results. Our framework reveals common features of brain activation in a population, as a new, efficient fMRI analysis method.

Functional connectome fingerprinting: identifying individuals using patterns of brain connectivity.

PubMed

Finn, Emily S; Shen, Xilin; Scheinost, Dustin; Rosenberg, Monica D; Huang, Jessica; Chun, Marvin M; Papademetris, Xenophon; Constable, R Todd

2015-11-01

Functional magnetic resonance imaging (fMRI) studies typically collapse data from many subjects, but brain functional organization varies between individuals. Here we establish that this individual variability is both robust and reliable, using data from the Human Connectome Project to demonstrate that functional connectivity profiles act as a 'fingerprint' that can accurately identify subjects from a large group. Identification was successful across scan sessions and even between task and rest conditions, indicating that an individual's connectivity profile is intrinsic, and can be used to distinguish that individual regardless of how the brain is engaged during imaging. Characteristic connectivity patterns were distributed throughout the brain, but the frontoparietal network emerged as most distinctive. Furthermore, we show that connectivity profiles predict levels of fluid intelligence: the same networks that were most discriminating of individuals were also most predictive of cognitive behavior. Results indicate the potential to draw inferences about single subjects on the basis of functional connectivity fMRI.

[Developmental neurotoxicity of industrial chemicals].

PubMed

Labie, Dominique

2007-10-01

"A Silent Pandemic : Industrial Chemicals Are Impairing the Brain Development of Children Worldwide" Fetal and early childhood exposures to industrial chemicals in the environment can damage the developing brain and can lead to neurodevelopmental disorders (NDDs)--autism, attention deficit disorder (ADHD), and mental retardation. In a new review study, published in The Lancet, Philip Grandjean and Philip Landrigan from the Harvard School of Public Health systematically examined publicly available data on chemical toxicity in order to identify the industrial chemicals that are the most likely to damage the developing brain. The researchers found that 202 industrial chemicals have the capacity to damage the human brain, and they conclude that chemical pollution may have harmed the brains of millions of children worldwide. The authors conclude further that the toxic effects of industrial chemicals on children have generally been overlooked. In North Amercia, the commission for environmental cooperation, and in European Union the DEVNERTOX projects had reached to the same conclusions. We analyse this review and discuss these rather pessimistic conclusions.

Individual Brain Charting, a high-resolution fMRI dataset for cognitive mapping.

PubMed

Pinho, Ana Luísa; Amadon, Alexis; Ruest, Torsten; Fabre, Murielle; Dohmatob, Elvis; Denghien, Isabelle; Ginisty, Chantal; Becuwe-Desmidt, Séverine; Roger, Séverine; Laurier, Laurence; Joly-Testault, Véronique; Médiouni-Cloarec, Gaëlle; Doublé, Christine; Martins, Bernadette; Pinel, Philippe; Eger, Evelyn; Varoquaux, Gaël; Pallier, Christophe; Dehaene, Stanislas; Hertz-Pannier, Lucie; Thirion, Bertrand

2018-06-12

Functional Magnetic Resonance Imaging (fMRI) has furthered brain mapping on perceptual, motor, as well as higher-level cognitive functions. However, to date, no data collection has systematically addressed the functional mapping of cognitive mechanisms at a fine spatial scale. The Individual Brain Charting (IBC) project stands for a high-resolution multi-task fMRI dataset that intends to provide the objective basis toward a comprehensive functional atlas of the human brain. The data refer to a cohort of 12 participants performing many different tasks. The large amount of task-fMRI data on the same subjects yields a precise mapping of the underlying functions, free from both inter-subject and inter-site variability. The present article gives a detailed description of the first release of the IBC dataset. It comprises a dozen of tasks, addressing both low- and high- level cognitive functions. This openly available dataset is thus intended to become a reference for cognitive brain mapping.

Measuring electrophysiological connectivity by power envelope correlation: a technical review on MEG methods

NASA Astrophysics Data System (ADS)

O'Neill, George C.; Barratt, Eleanor L.; Hunt, Benjamin A. E.; Tewarie, Prejaas K.; Brookes, Matthew J.

2015-11-01

The human brain can be divided into multiple areas, each responsible for different aspects of behaviour. Healthy brain function relies upon efficient connectivity between these areas and, in recent years, neuroimaging has been revolutionised by an ability to estimate this connectivity. In this paper we discuss measurement of network connectivity using magnetoencephalography (MEG), a technique capable of imaging electrophysiological brain activity with good (~5 mm) spatial resolution and excellent (~1 ms) temporal resolution. The rich information content of MEG facilitates many disparate measures of connectivity between spatially separate regions and in this paper we discuss a single metric known as power envelope correlation. We review in detail the methodology required to measure power envelope correlation including (i) projection of MEG data into source space, (ii) removing confounds introduced by the MEG inverse problem and (iii) estimation of connectivity itself. In this way, we aim to provide researchers with a description of the key steps required to assess envelope based functional networks, which are thought to represent an intrinsic mode of coupling in the human brain. We highlight the principal findings of the techniques discussed, and furthermore, we show evidence that this method can probe how the brain forms and dissolves multiple transient networks on a rapid timescale in order to support current processing demand. Overall, power envelope correlation offers a unique and verifiable means to gain novel insights into network coordination and is proving to be of significant value in elucidating the neural dynamics of the human connectome in health and disease.

Default, Cognitive, and Affective Brain Networks in Human Tinnitus

DTIC Science & Technology

2014-10-01

Tinnitus PRINCIPAL INVESTIGATOR: Jennifer R. Melcher, PhD CONTRACTING ORGANIZATION: Massachusetts Eye and Ear Infirmary Boston... Tinnitus 5b. GRANT NUMBER 5c. PROGRAM ELEMENT NUMBER 6. AUTHOR(S) Jennifer R Melcher, PI 5d. PROJECT NUMBER 5e. TASK NUMBER...for Public Release; Distribution Unlimited 13. SUPPLEMENTARY NOTES 14. ABSTRACT Tinnitus is a major health problem among those currently and

Direct phase projection and transcranial focusing of ultrasound for brain therapy.

PubMed

Pinton, Gianmarco F; Aubry, Jean-Francois; Tanter, Mickaël

2012-06-01

Ultrasound can be used to noninvasively treat the human brain with hyperthermia by focusing through the skull. To obtain an accurate focus, especially at high frequencies (>500 kHz), the phase of the transmitted wave must be modified to correct the aberrations introduced by the patient's individual skull morphology. Currently, three-dimensional finite-difference time-domain simulations are used to model a point source at the target. The outward-propagating wave crosses the measured representation of the human skull and is recorded at the therapy array transducer locations. The signal is then time reversed and experimentally transmitted back to its origin. These simulations are resource intensive and add a significant delay to treatment planning. Ray propagation is computationally efficient because it neglects diffraction and only describes two propagation parameters: the wave's direction and the phase. We propose a minimal method that is based only on the phase. The phase information is projected from the external skull surface to the array locations. This replaces computationally expensive finite-difference computations with an almost instantaneous direct phase projection calculation. For the five human skull samples considered, the phase distribution outside of the skull is shown to vary by less than λ/20 as it propagates over a 5 cm distance and the validity of phase projection is established over these propagation distances. The phase aberration introduced by the skull is characterized and is shown to have a good correspondence with skull morphology. The shape of this aberration is shown to have little variation with propagation distance. The focusing quality with the proposed phase-projection algorithm is shown to be indistinguishable from the gold-standard full finite-difference simulation. In conclusion, a spherical wave that is aberrated by the skull has a phase propagation that can be accurately described as radial, even after it has been distorted. By combining finite-difference simulations with a phase-projection algorithm, the time required for treatment planning is significantly reduced. The correlation length of the phase is used to validate the algorithm and it can also be used to provide guiding parameters for clinical array transducer design in terms of transducer spacing and phase error.

A neuronal morphologic type unique to humans and great apes

PubMed Central

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

1999-01-01

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

Functional brain networks related to individual differences in human intelligence at rest.

PubMed

Hearne, Luke J; Mattingley, Jason B; Cocchi, Luca

2016-08-26

Intelligence is a fundamental ability that sets humans apart from other animal species. Despite its importance in defining human behaviour, the neural networks responsible for intelligence are not well understood. The dominant view from neuroimaging work suggests that intelligent performance on a range of tasks is underpinned by segregated interactions in a fronto-parietal network of brain regions. Here we asked whether fronto-parietal interactions associated with intelligence are ubiquitous, or emerge from more widespread associations in a task-free context. First we undertook an exploratory mapping of the existing literature on functional connectivity associated with intelligence. Next, to empirically test hypotheses derived from the exploratory mapping, we performed network analyses in a cohort of 317 unrelated participants from the Human Connectome Project. Our results revealed a novel contribution of across-network interactions between default-mode and fronto-parietal networks to individual differences in intelligence at rest. Specifically, we found that greater connectivity in the resting state was associated with higher intelligence scores. Our findings highlight the need to broaden the dominant fronto-parietal conceptualisation of intelligence to encompass more complex and context-specific network dynamics.

Human Pluripotent Stem-Cell-Derived Cortical Neurons Integrate Functionally into the Lesioned Adult Murine Visual Cortex in an Area-Specific Way.

PubMed

Espuny-Camacho, Ira; Michelsen, Kimmo A; Linaro, Daniele; Bilheu, Angéline; Acosta-Verdugo, Sandra; Herpoel, Adèle; Giugliano, Michele; Gaillard, Afsaneh; Vanderhaeghen, Pierre

2018-05-29

The transplantation of pluripotent stem-cell-derived neurons constitutes a promising avenue for the treatment of several brain diseases. However, their potential for the repair of the cerebral cortex remains unclear, given its complexity and neuronal diversity. Here, we show that human visual cortical cells differentiated from embryonic stem cells can be transplanted and can integrate successfully into the lesioned mouse adult visual cortex. The transplanted human neurons expressed the appropriate repertoire of markers of six cortical layers, projected axons to specific visual cortical targets, and were synaptically active within the adult brain. Moreover, transplant maturation and integration were much less efficient following transplantation into the lesioned motor cortex, as previously observed for transplanted mouse cortical neurons. These data constitute an important milestone for the potential use of human PSC-derived cortical cells for the reassembly of cortical circuits and emphasize the importance of cortical areal identity for successful transplantation. Copyright © 2018 The Author(s). Published by Elsevier Inc. All rights reserved.

Individual differences and time-varying features of modular brain architecture.

PubMed

Liao, Xuhong; Cao, Miao; Xia, Mingrui; He, Yong

2017-05-15

Recent studies have suggested that human brain functional networks are topologically organized into functionally specialized but inter-connected modules to facilitate efficient information processing and highly flexible cognitive function. However, these studies have mainly focused on group-level network modularity analyses using "static" functional connectivity approaches. How these extraordinary modular brain structures vary across individuals and spontaneously reconfigure over time remain largely unknown. Here, we employed multiband resting-state functional MRI data (N=105) from the Human Connectome Project and a graph-based modularity analysis to systematically investigate individual variability and dynamic properties in modular brain networks. We showed that the modular structures of brain networks dramatically vary across individuals, with higher modular variability primarily in the association cortex (e.g., fronto-parietal and attention systems) and lower variability in the primary systems. Moreover, brain regions spontaneously changed their module affiliations on a temporal scale of seconds, which cannot be simply attributable to head motion and sampling error. Interestingly, the spatial pattern of intra-subject dynamic modular variability largely overlapped with that of inter-subject modular variability, both of which were highly reproducible across repeated scanning sessions. Finally, the regions with remarkable individual/temporal modular variability were closely associated with network connectors and the number of cognitive components, suggesting a potential contribution to information integration and flexible cognitive function. Collectively, our findings highlight individual modular variability and the notable dynamic characteristics in large-scale brain networks, which enhance our understanding of the neural substrates underlying individual differences in a variety of cognition and behaviors. Copyright © 2017 Elsevier Inc. All rights reserved.

Studying the Brain in a Dish: 3D Cell Culture Models of Human Brain Development and Disease.

PubMed

Brown, Juliana; Quadrato, Giorgia; Arlotta, Paola

2018-01-01

The study of the cellular and molecular processes of the developing human brain has been hindered by access to suitable models of living human brain tissue. Recently developed 3D cell culture models offer the promise of studying fundamental brain processes in the context of human genetic background and species-specific developmental mechanisms. Here, we review the current state of 3D human brain organoid models and consider their potential to enable investigation of complex aspects of human brain development and the underpinning of human neurological disease. © 2018 Elsevier Inc. All rights reserved.

Remote effects of intermittent theta burst stimulation of the human pharyngeal motor system

PubMed Central

Mistry, Satish; Michou, Emilia; Rothwell, John; Hamdy, Shaheen

2015-01-01

Intermittent theta burst stimulation (iTBS) is a novel, non-invasive form of brain stimulation capable of facilitating excitability of the human primary motor cortex with therapeutic potential in the treatment of neurological conditions, such as multiple sclerosis. The objectives of this study were to evaluate the effects of iTBS on cortical properties in the human pharyngeal motor system. Transcranial magnetic stimulation (TMS)-evoked pharyngeal motor responses were recorded via a swallowed intra-luminal catheter and used to assess motor cortical pathways to the pharynx in both hemispheres before and for up to 90 min after iTBS in 15 healthy adults (nine male/six female, 22–59 years old). Active/sham iTBS comprised 600 intermittent repetitive TMS pulses, delivered in a double-blind pseudo-randomised order over each hemisphere on separate days at least 1 week apart. Abductor pollicis brevis (APB) recordings were used as control. Hemispheric interventional data were compared with sham using repeated-measures anova. iTBS was delivered at an average intensity of 43 ± 1% of stimulator output. Compared with sham, iTBS to the hemisphere with stronger pharyngeal projections induced increased responses only in the contralateral weaker projection 60–90 min post-iTBS (maximum 54 ± 19%, P ≤ 0.007), with no change in stronger hemisphere responses. By contrast, iTBS to weaker projections had no significant effects (P = 0.39) on either hemisphere. APB responses similarly did not change significantly (P = 0.78) across all study arms. We conclude that iTBS can induce remote changes in corticobulbar excitability. While further studies will clarify the extent of these changes, iTBS holds promise as a potential treatment for dysphagia after unilateral brain damage. PMID:22640033

Assistance Technology Research Center

DTIC Science & Technology

2003-02-01

and perhaps modifying - some social behaviors of people with autism . "* Leveraging ancillary funding from both NIDRR and NSF, Anthrotronix is three...to independence for many individuals with traumatic brain injury, stroke, and autism . This project will develop virtual environments, using the...pentapeptide consensus sequence of the human NMDA receptor NR2a and NR2b subunits. Magnetic resonance imaging (MRI) will be performed for evaluation of

Modeling Zombie Outbreaks: A Problem-Based Approach to Improving Mathematics One Brain at a Time

ERIC Educational Resources Information Center

Lewis, Matthew; Powell, James A.

2016-01-01

A great deal of educational literature has focused on problem-based learning (PBL) in mathematics at the primary and secondary level, but arguably there is an even greater need for PBL in college math courses. We present a project centered around the Humans versus Zombies moderated tag game played on the Utah State University campus. We discuss…

Freeze for action: neurobiological mechanisms in animal and human freezing

PubMed Central

2017-01-01

Upon increasing levels of threat, animals activate qualitatively different defensive modes, including freezing and active fight-or-flight reactions. Whereas freezing is a form of behavioural inhibition accompanied by parasympathetically dominated heart rate deceleration, fight-or-flight reactions are associated with sympathetically driven heart rate acceleration. Despite the potential relevance of freezing for human stress-coping, its phenomenology and neurobiological underpinnings remain largely unexplored in humans. Studies in rodents have shown that freezing depends on amygdala projections to the brainstem (periaqueductal grey). Recent neuroimaging studies in humans have indicated that similar brain regions may be involved in human freezing. In addition, flexibly shifting between freezing and active defensive modes is critical for adequate stress-coping and relies on fronto-amygdala connections. This review paper presents a model detailing these neural mechanisms involved in freezing and the shift to fight-or-flight action. Freezing is not a passive state but rather a parasympathetic brake on the motor system, relevant to perception and action preparation. Study of these defensive responses in humans may advance insights into human stress-related psychopathologies characterized by rigidity in behavioural stress reactions. The paper therefore concludes with a research agenda to stimulate translational animal–human research in this emerging field of human defensive stress responses. This article is part of the themed issue ‘Movement suppression: brain mechanisms for stopping and stillness’. PMID:28242739

A novel method for fast imaging of brain function, non-invasively, with light

NASA Astrophysics Data System (ADS)

Chance, Britton; Anday, Endla; Nioka, Shoko; Zhou, Shuoming; Hong, Long; Worden, Katherine; Li, C.; Murray, T.; Ovetsky, Y.; Pidikiti, D.; Thomas, R.

1998-05-01

Imaging of the human body by any non-invasive technique has been an appropriate goal of physics and medicine, and great success has been obtained with both Magnetic Resonance Imaging (MRI) and Positron Emission Tomography (PET) in brain imaging. Non-imaging responses to functional activation using near infrared spectroscopy of brain (fNIR) obtained in 1993 (Chance, et al. [1]) and in 1994 (Tamura, et al. [2]) are now complemented with images of pre-frontal and parietal stimulation in adults and pre-term neonates in this communication (see also [3]). Prior studies used continuous [4], pulsed [3] or modulated [5] light. The amplitude and phase cancellation of optical patterns as demonstrated for single source detector pairs affords remarkable sensitivity of small object detection in model systems [6]. The methods have now been elaborated with multiple source detector combinations (nine sources, four detectors). Using simple back projection algorithms it is now possible to image sensorimotor and cognitive activation of adult and pre- and full-term neonate human brain function in times < 30 sec and with two dimensional resolutions of < 1 cm in two dimensional displays. The method can be used in evaluation of adult and neonatal cerebral dysfunction in a simple, portable and affordable method that does not require immobilization, as contrasted to MRI and PET.

Segmentation of the Canine Corpus Callosum using Diffusion Tensor Imaging Tractography

PubMed Central

Pierce, T.T.; Calabrese, E.; White, L.E.; Chen, S.D.; Platt, S.R.; Provenzale, J.M.

2014-01-01

Background We set out to determine functional white matter (WM) connections passing through the canine corpus callosum useful for subsequent studies of canine brains that serve as models for human WM pathway disease. Based on prior studies, we anticipated that the anterior corpus callosum would send projections to the anterior cerebral cortex while progressively posterior segments would send projections to more posterior cortex. Methods A post mortem canine brain was imaged using a 7T MRI producing 100 micron isotropic resolution DTI analyzed by tractography. Using ROIs within cortical locations, which were confirmed by a Nissl stain that identified distinct cortical architecture, we successfully identified 6 important WM pathways. We also compared fractional anisotropy (FA), apparent diffusion coefficient (ADC), radial diffusivity (RD), and axial diffusivity (AD) in tracts passing through the genu and splenium. Results Callosal fibers were organized based upon cortical destination, i.e. fibers from the genu project to the frontal cortex. Histologic results identified the motor cortex based on cytoarchitectonic criteria that allowed placement of ROIs to discriminate between frontal and parietal lobes. We also identified cytoarchitecture typical of the orbital frontal, anterior frontal, and occipital regions and placed ROIs accordingly. FA, ADC, RD and AD values were all higher in posterior corpus callosum fiber tracts. Conclusions Using 6 cortical ROIs, we identified 6 major white matter tracts that reflect major functional divisions of the cerebral hemispheres and we derived quantitative values that can be used for study of canine models of human WM pathological states. PMID:24370161

What boxing tells us about repetitive head trauma and the brain.

PubMed

Bernick, Charles; Banks, Sarah

2013-01-01

Boxing and other combat sports may serve as a human model to study the effects of repetitive head trauma on brain structure and function. The initial description of what is now known as chronic traumatic encephalopathy (CTE) was reported in boxers in 1928. In the ensuing years, studies examining boxers have described the clinical features of CTE, its relationship to degree of exposure to fighting, and an array of radiologic findings. The field has been hampered by issues related to study design, lack of longitudinal follow-up, and absence of agreed-upon clinical criteria for CTE. A recently launched prospective cohort study of professional fighters, the Professional Fighters Brain Health Study, attempts to overcome some of the problems in studying fighters. Here, we review the cross-sectional results from the first year of the project.

Constructing fine-granularity functional brain network atlases via deep convolutional autoencoder.

PubMed

Zhao, Yu; Dong, Qinglin; Chen, Hanbo; Iraji, Armin; Li, Yujie; Makkie, Milad; Kou, Zhifeng; Liu, Tianming

2017-12-01

State-of-the-art functional brain network reconstruction methods such as independent component analysis (ICA) or sparse coding of whole-brain fMRI data can effectively infer many thousands of volumetric brain network maps from a large number of human brains. However, due to the variability of individual brain networks and the large scale of such networks needed for statistically meaningful group-level analysis, it is still a challenging and open problem to derive group-wise common networks as network atlases. Inspired by the superior spatial pattern description ability of the deep convolutional neural networks (CNNs), a novel deep 3D convolutional autoencoder (CAE) network is designed here to extract spatial brain network features effectively, based on which an Apache Spark enabled computational framework is developed for fast clustering of larger number of network maps into fine-granularity atlases. To evaluate this framework, 10 resting state networks (RSNs) were manually labeled from the sparsely decomposed networks of Human Connectome Project (HCP) fMRI data and 5275 network training samples were obtained, in total. Then the deep CAE models are trained by these functional networks' spatial maps, and the learned features are used to refine the original 10 RSNs into 17 network atlases that possess fine-granularity functional network patterns. Interestingly, it turned out that some manually mislabeled outliers in training networks can be corrected by the deep CAE derived features. More importantly, fine granularities of networks can be identified and they reveal unique network patterns specific to different brain task states. By further applying this method to a dataset of mild traumatic brain injury study, it shows that the technique can effectively identify abnormal small networks in brain injury patients in comparison with controls. In general, our work presents a promising deep learning and big data analysis solution for modeling functional connectomes, with fine granularities, based on fMRI data. Copyright © 2017 Elsevier B.V. All rights reserved.

Functional brain networks reconstruction using group sparsity-regularized learning.

PubMed

Zhao, Qinghua; Li, Will X Y; Jiang, Xi; Lv, Jinglei; Lu, Jianfeng; Liu, Tianming

2018-06-01

Investigating functional brain networks and patterns using sparse representation of fMRI data has received significant interests in the neuroimaging community. It has been reported that sparse representation is effective in reconstructing concurrent and interactive functional brain networks. To date, most of data-driven network reconstruction approaches rarely take consideration of anatomical structures, which are the substrate of brain function. Furthermore, it has been rarely explored whether structured sparse representation with anatomical guidance could facilitate functional networks reconstruction. To address this problem, in this paper, we propose to reconstruct brain networks utilizing the structure guided group sparse regression (S2GSR) in which 116 anatomical regions from the AAL template, as prior knowledge, are employed to guide the network reconstruction when performing sparse representation of whole-brain fMRI data. Specifically, we extract fMRI signals from standard space aligned with the AAL template. Then by learning a global over-complete dictionary, with the learned dictionary as a set of features (regressors), the group structured regression employs anatomical structures as group information to regress whole brain signals. Finally, the decomposition coefficients matrix is mapped back to the brain volume to represent functional brain networks and patterns. We use the publicly available Human Connectome Project (HCP) Q1 dataset as the test bed, and the experimental results indicate that the proposed anatomically guided structure sparse representation is effective in reconstructing concurrent functional brain networks.

The elephant brain in numbers

PubMed Central

Herculano-Houzel, Suzana; Avelino-de-Souza, Kamilla; Neves, Kleber; Porfírio, Jairo; Messeder, Débora; Mattos Feijó, Larissa; Maldonado, José; Manger, Paul R.

2014-01-01

What explains the superior cognitive abilities of the human brain compared to other, larger brains? Here we investigate the possibility that the human brain has a larger number of neurons than even larger brains by determining the cellular composition of the brain of the African elephant. We find that the African elephant brain, which is about three times larger than the human brain, contains 257 billion (109) neurons, three times more than the average human brain; however, 97.5% of the neurons in the elephant brain (251 billion) are found in the cerebellum. This makes the elephant an outlier in regard to the number of cerebellar neurons compared to other mammals, which might be related to sensorimotor specializations. In contrast, the elephant cerebral cortex, which has twice the mass of the human cerebral cortex, holds only 5.6 billion neurons, about one third of the number of neurons found in the human cerebral cortex. This finding supports the hypothesis that the larger absolute number of neurons in the human cerebral cortex (but not in the whole brain) is correlated with the superior cognitive abilities of humans compared to elephants and other large-brained mammals. PMID:24971054

Cerebellar neurocontroller project, for aerospace applications, in a civilian neurocomputing initiative in the 'decade of the brain'

NASA Technical Reports Server (NTRS)

Pellionisz, Andras J.; Jorgensen, Charles C.; Werbos, Paul J.

1992-01-01

A key question is how to utilize civilian government agencies along with an industrial consortium to successfully complement the so far primarily defense-oriented neural network research. Civilian artificial neural system projects, such as artificial cerebellar neurocontrollers aimed at duplicating nature's existing neural network solutions for adaptive sensorimotor coordination, are proposed by such a synthesis. The cerebellum provides an intelligent interface between higher possibly symbolic levels of human intelligence and repetitious demands of real world conventional controllers. The generation of such intelligent interfaces could be crucial to the economic feasibility of the human settlement of space and an improvement in telerobotics techniques to permit the cost-effective exploitation of nonterrestrial materials and planetary exploration and monitoring. The authors propose a scientific framework within which such interagency activities could effectively cooperate.

Quetiapine modulates functional connectivity in brain aggression networks.

PubMed

Klasen, Martin; Zvyagintsev, Mikhail; Schwenzer, Michael; Mathiak, Krystyna A; Sarkheil, Pegah; Weber, René; Mathiak, Klaus

2013-07-15

Aggressive behavior is associated with dysfunctions in an affective regulation network encompassing amygdala and prefrontal areas such as orbitofrontal (OFC), anterior cingulate (ACC), and dorsolateral prefrontal cortex (DLPFC). In particular, prefrontal regions have been postulated to control amygdala activity by inhibitory projections, and this process may be disrupted in aggressive individuals. The atypical antipsychotic quetiapine successfully attenuates aggressive behavior in various disorders; the underlying neural processes, however, are unknown. A strengthened functional coupling in the prefrontal-amygdala system may account for these anti-aggressive effects. An inhibition of this network has been reported for virtual aggression in violent video games as well. However, there have been so far no in-vivo observations of pharmacological influences on corticolimbic projections during human aggressive behavior. In a double-blind, placebo-controlled study, quetiapine and placebo were administered for three successive days prior to an fMRI experiment. In this experiment, functional brain connectivity was assessed during virtual aggressive behavior in a violent video game and an aggression-free control task in a non-violent modification. Quetiapine increased the functional connectivity of ACC and DLPFC with the amygdala during virtual aggression, whereas OFC-amygdala coupling was attenuated. These effects were observed neither for placebo nor for the non-violent control. These results demonstrate for the first time a pharmacological modification of aggression-related human brain networks in a naturalistic setting. The violence-specific modulation of prefrontal-amygdala networks appears to control aggressive behavior and provides a neurobiological model for the anti-aggressive effects of quetiapine. Copyright © 2013 Elsevier Inc. All rights reserved.

An ANOVA approach for statistical comparisons of brain networks.

PubMed

Fraiman, Daniel; Fraiman, Ricardo

2018-03-16

The study of brain networks has developed extensively over the last couple of decades. By contrast, techniques for the statistical analysis of these networks are less developed. In this paper, we focus on the statistical comparison of brain networks in a nonparametric framework and discuss the associated detection and identification problems. We tested network differences between groups with an analysis of variance (ANOVA) test we developed specifically for networks. We also propose and analyse the behaviour of a new statistical procedure designed to identify different subnetworks. As an example, we show the application of this tool in resting-state fMRI data obtained from the Human Connectome Project. We identify, among other variables, that the amount of sleep the days before the scan is a relevant variable that must be controlled. Finally, we discuss the potential bias in neuroimaging findings that is generated by some behavioural and brain structure variables. Our method can also be applied to other kind of networks such as protein interaction networks, gene networks or social networks.

Brain Tocopherols Related to Alzheimer Disease Neuropathology in Humans

PubMed Central

Morris, Martha Clare; Schneider, Julie A; Li, Hong; Tangney, Christy C; Nag, Sukrit; Bennett, David A; Honer, William G.; Barnes, Lisa

2014-01-01

Randomized trials of α-tocopherol supplements on cognitive decline are negative whereas studies of dietary tocopherols show benefit. We investigated these inconsistencies by analyzing the relations of α- and γ-tocopherol brain concentrations to Alzheimer disease (AD) neuropathology among 115 deceased participants of the prospective Rush Memory and Aging Project. Associations of amyloid load and neurofibrillary tangle severity with brain tocopherol concentrations were examined in separate adjusted linear regression models. γ-tocopherol concentrations were associated with lower amyloid load (β= −2.10; p=.002) and lower neurofibrillary tangle severity (β= −1.16; p=0.02). Concentrations of α-tocopherol were not associated with AD neuropathology except as modified by γ-tocopherol: high α-tocopherol was associated with higher amyloid load when γ-tocopherol levels were low and with lower amyloid levels when γ-tocopherol levels were high (P for interaction=0.03). Brain concentrations of γ- and α-tocopherols may be associated with AD neuropathology in interrelated, complex ways. Randomized trials should consider the contribution of γ-tocopherol. PMID:24589434

White matter integrity in brain networks relevant to anxiety and depression: evidence from the human connectome project dataset.

PubMed

De Witte, Nele A J; Mueller, Sven C

2017-12-01

Anxiety and depression are associated with altered communication within global brain networks and between these networks and the amygdala. Functional connectivity studies demonstrate an effect of anxiety and depression on four critical brain networks involved in top-down attentional control (fronto-parietal network; FPN), salience detection and error monitoring (cingulo-opercular network; CON), bottom-up stimulus-driven attention (ventral attention network; VAN), and default mode (default mode network; DMN). However, structural evidence on the white matter (WM) connections within these networks and between these networks and the amygdala is lacking. The current study in a large healthy sample (n = 483) observed that higher trait anxiety-depression predicted lower WM integrity in the connections between amygdala and specific regions of the FPN, CON, VAN, and DMN. We discuss the possible consequences of these anatomical alterations for cognitive-affective functioning and underscore the need for further theory-driven research on individual differences in anxiety and depression on brain structure.

All the Vice Chancellor’s Neuroscientists: Unity to Achieve Success in Solving Malaysia’s Diseases via Upgrading Clinical Services and Neuroscience Research

PubMed Central

Abdullah, Jafri Malin

2013-01-01

President Obama of the United States of America announced this April the Brain Research Through Advancing Innovative Neurotechnologies (BRAIN for short) investment, while Professor Henry Markram’s team based in the European Union will spend over a billion euros on the Human Brain Project, breaking through the unknowns in the fifth science of the decade: Neuroscience. Malaysia's growth in the same field needs to be augmented, and thus the Universiti Sains Malaysia’s vision is to excel in the field of clinical brain sciences, mind sciences and neurosciences. This will naturally bring up the level of research in the country simultaneously. Thus, a center was recently established to coordinate this venture. The four-year Integrated Neuroscience Program established recently will be a sustainable source of neuroscientists for the country. We hope to establish ourselves by 2020 as a global university with neurosciences research as an important flagship. PMID:23966818

microRNA in Cerebral Spinal Fluid as Biomarkers of Alzheimer’s Disease Risk After Brain Injury

DTIC Science & Technology

2017-08-01

anticipate that the regulatory delays will impact expenditures for this project. Significant changes in use or care of human subjects, vertebrate...PRINCIPAL INVESTIGATOR: Dr. Joseph Quinn CONTRACTING ORGANIZATION: Oregon Health & Science University Portland, OR 97239-3098 REPORT DATE: August 2017...7. PERFORMING ORGANIZATION NAME(S) AND ADDRESS(ES) AND ADDRESS(ES) 8. PERFORMING ORGANIZATION REPORT NUMBER OREGON HEALTH & SCIENCE UNIVERSITY

Molecular Probe Analysis of Mammalian Brain Acetylcholinesterase

DTIC Science & Technology

1988-09-27

Project and Degrees Awarded During this Reporting Period: Judith K. Marquis, Principal Investigator Thomas Biagioni , Senior Research Technician Robert...binding sites in nerve membrane vesicles. Comp. Biochem. Physiol. 80C: 203-205 (1985). 5. Volpe, L.S., T.M. Biagioni & J.K. Marquis: In vitro modulation of...Saxena, Vol. 6(1988Y.8 11. Marquis, J.K. & T.M. Biagioni : Selective inhibition of acetylcholinesterase and butyrylcholinesterase in human plasma

Contextualizing neuro-collaborations: reflections on a transdisciplinary fMRI lie detection experiment

PubMed Central

Littlefield, Melissa M.; Fitzgerald, Des; Knudsen, Kasper; Tonks, James; Dietz, Martin J.

2014-01-01

Recent neuroscience initiatives (including the E.U.’s Human Brain Project and the U.S.’s BRAIN Initiative) have reinvigorated discussions about the possibilities for transdisciplinary collaboration between the neurosciences, the social sciences, and the humanities. As STS scholars have argued for decades, however, such inter- and transdisciplinary collaborations are potentially fraught with tensions between researchers. This essay build on such claims by arguing that the tensions of transdisciplinary research also exist within researchers’ own experiences of working between disciplines - a phenomenon that we call “disciplinary double consciousness” (DDC). Building on previous work that has characterized similar spaces (and especially on the Critical Neuroscience literature), we argue that “neuro-collaborations” inevitably engage researchers in DDC - a phenomenon that allows us to explore the useful dissonance that researchers can experience when working between a “home” discipline and a secondary discipline. Our case study is a five-year research project in functional magnetic resonance imaging (fMRI) lie detection involving a transdisciplinary research team made up of social scientists, a neuroscientist, and a humanist. In addition to theorizing neuro-collaborations from the inside-out, this essay presents practical suggestions for developing transdisciplinary infrastructures that could support future neuro-collaborations. PMID:24744713

Neurotechnology: expanding opportunities for funding at the National Institute of Mental Health.

PubMed

Huerta, M F; Curvey, M F; Koslow, S H

1994-10-01

The National Institute of Mental Health recognizes the importance that creative development of technology and methodology play in brain and behavioral science research. This institute is making major efforts to support such development through specific initiatives, like the Human Brain Project. In addition, this Institute is actively building bridges between business and academic research communities to make optical use of funds for the research and development of commercially viable technologies relevant to all aspects of the Institute's mission through the Small Business Innovation Research and Small Business Technology Transfer Programs. Together, these efforts will culminate in a more vigorous scientific enterprise, and ultimately benefit the entire mental health community and society.

Neuroanatomical Diversity of Corpus Callosum and Brain Volume in Autism: Meta-analysis, Analysis of the Autism Brain Imaging Data Exchange Project, and Simulation.

PubMed

Lefebvre, Aline; Beggiato, Anita; Bourgeron, Thomas; Toro, Roberto

2015-07-15

Patients with autism have been often reported to have a smaller corpus callosum (CC) than control subjects. We conducted a meta-analysis of the literature, analyzed the CC in 694 subjects of the Autism Brain Imaging Data Exchange project, and performed computer simulations to study the effect of different analysis strategies. Our meta-analysis suggested a group difference in CC size; however, the studies were heavily underpowered (20% power to detect Cohen's d = .3). In contrast, we did not observe significant differences in the Autism Brain Imaging Data Exchange cohort, despite having achieved 99% power. However, we observed that CC scaled nonlinearly with brain volume (BV): large brains had a proportionally smaller CC. Our simulations showed that because of this nonlinearity, CC normalization could not control for eventual BV differences, but using BV as a covariate in a linear model would. We also observed a weaker correlation of IQ and BV in cases compared with control subjects. Our simulations showed that matching populations by IQ could then induce artifactual BV differences. The lack of statistical power in the previous literature prevents us from establishing the reality of the claims of a smaller CC in autism, and our own analyses did not find any. However, the nonlinear relationship between CC and BV and the different correlation between BV and IQ in cases and control subjects may induce artifactual differences. Overall, our results highlight the necessity for open data sharing to provide a more solid ground for the discovery of neuroimaging biomarkers within the context of the wide human neuroanatomical diversity. Copyright © 2015 Society of Biological Psychiatry. Published by Elsevier Inc. All rights reserved.

Functional brain networks related to individual differences in human intelligence at rest

PubMed Central

Hearne, Luke J.; Mattingley, Jason B.; Cocchi, Luca

2016-01-01

Intelligence is a fundamental ability that sets humans apart from other animal species. Despite its importance in defining human behaviour, the neural networks responsible for intelligence are not well understood. The dominant view from neuroimaging work suggests that intelligent performance on a range of tasks is underpinned by segregated interactions in a fronto-parietal network of brain regions. Here we asked whether fronto-parietal interactions associated with intelligence are ubiquitous, or emerge from more widespread associations in a task-free context. First we undertook an exploratory mapping of the existing literature on functional connectivity associated with intelligence. Next, to empirically test hypotheses derived from the exploratory mapping, we performed network analyses in a cohort of 317 unrelated participants from the Human Connectome Project. Our results revealed a novel contribution of across-network interactions between default-mode and fronto-parietal networks to individual differences in intelligence at rest. Specifically, we found that greater connectivity in the resting state was associated with higher intelligence scores. Our findings highlight the need to broaden the dominant fronto-parietal conceptualisation of intelligence to encompass more complex and context-specific network dynamics. PMID:27561736

Tissue microstructure features derived from anomalous diffusion measurements in magnetic resonance imaging.

PubMed

Yu, Qiang; Reutens, David; O'Brien, Kieran; Vegh, Viktor

2017-02-01

Tissue microstructure features, namely axon radius and volume fraction, provide important information on the function of white matter pathways. These parameters vary on the scale much smaller than imaging voxels (microscale) yet influence the magnetic resonance imaging diffusion signal at the image voxel scale (macroscale) in an anomalous manner. Researchers have already mapped anomalous diffusion parameters from magnetic resonance imaging data, but macroscopic variations have not been related to microscale influences. With the aid of a tissue model, we aimed to connect anomalous diffusion parameters to axon radius and volume fraction using diffusion-weighted magnetic resonance imaging measurements. An ex vivo human brain experiment was performed to directly validate axon radius and volume fraction measurements in the human brain. These findings were validated using electron microscopy. Additionally, we performed an in vivo study on nine healthy participants to map axon radius and volume fraction along different regions of the corpus callosum projecting into various cortical areas identified using tractography. We found a clear relationship between anomalous diffusion parameters and axon radius and volume fraction. We were also able to map accurately the trend in axon radius along the corpus callosum, and in vivo findings resembled the low-high-low-high behaviour in axon radius demonstrated previously. Axon radius and volume fraction measurements can potentially be used in brain connectivity studies and to understand the implications of white matter structure in brain diseases and disorders. Hum Brain Mapp 38:1068-1081, 2017. © 2016 Wiley Periodicals, Inc. © 2016 Wiley Periodicals, Inc.

Banking brain tissue for research.

PubMed

Klioueva, Natasja; Bovenberg, Jasper; Huitinga, Inge

2017-01-01

Well-characterized human brain tissue is crucial for scientific breakthroughs in research of the human brain and brain diseases. However, the collection, characterization, management, and accessibility of brain human tissue are rather complex. Well-characterized human brain tissue is often provided from private, sometimes small, brain tissue collections by (neuro)pathologic experts. However, to meet the increasing demand for human brain tissue from the scientific community, many professional brain-banking activities aiming at both neurologic and psychiatric diseases as well as healthy controls are currently being initiated worldwide. Professional biobanks are open-access and in many cases run donor programs. They are therefore costly and need effective business plans to guarantee long-term sustainability. Here we discuss the ethical, legal, managerial, and financial aspects of professional brain banks. Copyright © 2017 Elsevier B.V. All rights reserved.

Extendable supervised dictionary learning for exploring diverse and concurrent brain activities in task-based fMRI.

PubMed

Zhao, Shijie; Han, Junwei; Hu, Xintao; Jiang, Xi; Lv, Jinglei; Zhang, Tuo; Zhang, Shu; Guo, Lei; Liu, Tianming

2018-06-01

Recently, a growing body of studies have demonstrated the simultaneous existence of diverse brain activities, e.g., task-evoked dominant response activities, delayed response activities and intrinsic brain activities, under specific task conditions. However, current dominant task-based functional magnetic resonance imaging (tfMRI) analysis approach, i.e., the general linear model (GLM), might have difficulty in discovering those diverse and concurrent brain responses sufficiently. This subtraction-based model-driven approach focuses on the brain activities evoked directly from the task paradigm, thus likely overlooks other possible concurrent brain activities evoked during the information processing. To deal with this problem, in this paper, we propose a novel hybrid framework, called extendable supervised dictionary learning (E-SDL), to explore diverse and concurrent brain activities under task conditions. A critical difference between E-SDL framework and previous methods is that we systematically extend the basic task paradigm regressor into meaningful regressor groups to account for possible regressor variation during the information processing procedure in the brain. Applications of the proposed framework on five independent and publicly available tfMRI datasets from human connectome project (HCP) simultaneously revealed more meaningful group-wise consistent task-evoked networks and common intrinsic connectivity networks (ICNs). These results demonstrate the advantage of the proposed framework in identifying the diversity of concurrent brain activities in tfMRI datasets.

The Impact of Childhood Trauma on Brain Development: A Literature Review and Supporting Handouts

ERIC Educational Resources Information Center

Kirouac, Samantha; McBride, Dawn Lorraine

2009-01-01

This project provides a comprehensive overview of the research literature on the brain and how trauma impacts brain development, structures, and functioning. A basic exploration of childhood trauma is outlined in this project, as it is essential in making associations and connections to brain development. Childhood trauma is processed in the…

Multi-subject hierarchical inverse covariance modelling improves estimation of functional brain networks.

PubMed

Colclough, Giles L; Woolrich, Mark W; Harrison, Samuel J; Rojas López, Pedro A; Valdes-Sosa, Pedro A; Smith, Stephen M

2018-05-07

A Bayesian model for sparse, hierarchical, inver-covariance estimation is presented, and applied to multi-subject functional connectivity estimation in the human brain. It enables simultaneous inference of the strength of connectivity between brain regions at both subject and population level, and is applicable to fMRI, MEG and EEG data. Two versions of the model can encourage sparse connectivity, either using continuous priors to suppress irrelevant connections, or using an explicit description of the network structure to estimate the connection probability between each pair of regions. A large evaluation of this model, and thirteen methods that represent the state of the art of inverse covariance modelling, is conducted using both simulated and resting-state functional imaging datasets. Our novel Bayesian approach has similar performance to the best extant alternative, Ng et al.'s Sparse Group Gaussian Graphical Model algorithm, which also is based on a hierarchical structure. Using data from the Human Connectome Project, we show that these hierarchical models are able to reduce the measurement error in MEG beta-band functional networks by 10%, producing concomitant increases in estimates of the genetic influence on functional connectivity. Copyright © 2018. Published by Elsevier Inc.

Opposing Brain Differences in 16p11.2 Deletion and Duplication Carriers

PubMed Central

Qureshi, Abid Y.; Mueller, Sophia; Snyder, Abraham Z.; Mukherjee, Pratik; Berman, Jeffrey I.; Roberts, Timothy P.L.; Nagarajan, Srikantan S.; Spiro, John E.; Chung, Wendy K.; Sherr, Elliott H.

2014-01-01

Deletions and duplications of the recurrent ∼600 kb chromosomal BP4–BP5 region of 16p11.2 are associated with a broad variety of neurodevelopmental outcomes including autism spectrum disorder. A clue to the pathogenesis of the copy number variant (CNV)'s effect on the brain is that the deletion is associated with a head size increase, whereas the duplication is associated with a decrease. Here we analyzed brain structure in a clinically ascertained group of human deletion (N = 25) and duplication (N = 17) carriers from the Simons Variation in Individuals Project compared with age-matched controls (N = 29 and 33, respectively). Multiple brain measures showed increased size in deletion carriers and reduced size in duplication carriers. The effects spanned global measures of intracranial volume, brain size, compartmental measures of gray matter and white matter, subcortical structures, and the cerebellum. Quantitatively, the largest effect was on the thalamus, but the collective results suggest a pervasive rather than a selective effect on the brain. Detailed analysis of cortical gray matter revealed that cortical surface area displays a strong dose-dependent effect of CNV (deletion > control > duplication), whereas average cortical thickness is less affected. These results suggest that the CNV may exert its opposing influences through mechanisms that influence early stages of embryonic brain development. PMID:25143601

Normative brain size variation and brain shape diversity in humans.

PubMed

Reardon, P K; Seidlitz, Jakob; Vandekar, Simon; Liu, Siyuan; Patel, Raihaan; Park, Min Tae M; Alexander-Bloch, Aaron; Clasen, Liv S; Blumenthal, Jonathan D; Lalonde, Francois M; Giedd, Jay N; Gur, Ruben C; Gur, Raquel E; Lerch, Jason P; Chakravarty, M Mallar; Satterthwaite, Theodore D; Shinohara, Russell T; Raznahan, Armin

2018-06-15

Brain size variation over primate evolution and human development is associated with shifts in the proportions of different brain regions. Individual brain size can vary almost twofold among typically developing humans, but the consequences of this for brain organization remain poorly understood. Using in vivo neuroimaging data from more than 3000 individuals, we find that larger human brains show greater areal expansion in distributed frontoparietal cortical networks and related subcortical regions than in limbic, sensory, and motor systems. This areal redistribution recapitulates cortical remodeling across evolution, manifests by early childhood in humans, and is linked to multiple markers of heightened metabolic cost and neuronal connectivity. Thus, human brain shape is systematically coupled to naturally occurring variations in brain size through a scaling map that integrates spatiotemporally diverse aspects of neurobiology. Copyright © 2018 The Authors, some rights reserved; exclusive licensee American Association for the Advancement of Science. No claim to original U.S. Government Works.

I.V. infusion of brain-derived neurotrophic factor gene-modified human mesenchymal stem cells protects against injury in a cerebral ischemia model in adult rat.

PubMed

Nomura, T; Honmou, O; Harada, K; Houkin, K; Hamada, H; Kocsis, J D

2005-01-01

I.V. delivery of mesenchymal stem cells prepared from adult bone marrow reduces infarction size and ameliorates functional deficits in rat cerebral ischemia models. Administration of the brain-derived neurotrophic factor to the infarction site has also been demonstrated to be neuroprotective. To test the hypothesis that brain-derived neurotrophic factor contributes to the therapeutic benefits of mesenchymal stem cell delivery, we compared the efficacy of systemic delivery of human mesenchymal stem cells and human mesenchymal stem cells transfected with a fiber-mutant F/RGD adenovirus vector with a brain-derived neurotrophic factor gene (brain-derived neurotrophic factor-human mesenchymal stem cells). A permanent middle cerebral artery occlusion was induced by intraluminal vascular occlusion with a microfilament. Human mesenchymal stem cells and brain-derived neurotrophic factor-human mesenchymal stem cells were i.v. injected into the rats 6 h after middle cerebral artery occlusion. Lesion size was assessed at 6 h, 1, 3 and 7 days using MR imaging, and histological methods. Functional outcome was assessed using the treadmill stress test. Both human mesenchymal stem cells and brain-derived neurotrophic factor-human mesenchymal stem cells reduced lesion volume and elicited functional improvement compared with the control sham group, but the effect was greater in the brain-derived neurotrophic factor-human mesenchymal stem cell group. ELISA analysis of the infarcted hemisphere revealed an increase in brain-derived neurotrophic factor in the human mesenchymal stem cell groups, but a greater increase in the brain-derived neurotrophic factor-human mesenchymal stem cell group. These data support the hypothesis that brain-derived neurotrophic factor contributes to neuroprotection in cerebral ischemia and cellular delivery of brain-derived neurotrophic factor can be achieved by i.v. delivery of human mesenchymal stem cells.

Paranormal experience and the COMT dopaminergic gene: a preliminary attempt to associate phenotype with genotype using an underlying brain theory.

PubMed

Raz, Amir; Hines, Terence; Fossella, John; Castro, Daniella

2008-01-01

Paranormal belief and suggestibility seem related. Given our recent findings outlining a putative association between suggestibility and a specific dopaminergic genetic polymorphism, we hypothesized that similar exploratory genetic data may offer supplementary insights into a similar correlation with paranormal belief. With more affordable costs and better technology in the aftermath of the human genome project, genotyping is increasingly ubiquitous. Compelling brain theories guide specific research hypotheses as scientists begin to unravel tentative relationships between phenotype and genotype. In line with a dopaminergic brain theory, we tried to correlate a specific phenotype concerning paranormal belief with a dopaminergic gene (COMT) known for its involvement in prefrontal executive cognition and for a polymorphism that is positively correlated with suggestibility. Although our preliminary findings are inconclusive, the research approach we outline should pave the road to a more scientific account of elucidating paranormal belief.

The INIA19 Template and NeuroMaps Atlas for Primate Brain Image Parcellation and Spatial Normalization

PubMed Central

Rohlfing, Torsten; Kroenke, Christopher D.; Sullivan, Edith V.; Dubach, Mark F.; Bowden, Douglas M.; Grant, Kathleen A.; Pfefferbaum, Adolf

2012-01-01

The INIA19 is a new, high-quality template for imaging-based studies of non-human primate brains, created from high-resolution, T1-weighted magnetic resonance (MR) images of 19 rhesus macaque (Macaca mulatta) animals. Combined with the comprehensive cortical and sub-cortical label map of the NeuroMaps atlas, the INIA19 is equally suitable for studies requiring both spatial normalization and atlas label propagation. Population-averaged template images are provided for both the brain and the whole head, to allow alignment of the atlas with both skull-stripped and unstripped data, and thus to facilitate its use for skull stripping of new images. This article describes the construction of the template using freely available software tools, as well as the template itself, which is being made available to the scientific community (http://nitrc.org/projects/inia19/). PMID:23230398

Integrative biological analysis for neuropsychopharmacology.

PubMed

Emmett, Mark R; Kroes, Roger A; Moskal, Joseph R; Conrad, Charles A; Priebe, Waldemar; Laezza, Fernanda; Meyer-Baese, Anke; Nilsson, Carol L

2014-01-01

Although advances in psychotherapy have been made in recent years, drug discovery for brain diseases such as schizophrenia and mood disorders has stagnated. The need for new biomarkers and validated therapeutic targets in the field of neuropsychopharmacology is widely unmet. The brain is the most complex part of human anatomy from the standpoint of number and types of cells, their interconnections, and circuitry. To better meet patient needs, improved methods to approach brain studies by understanding functional networks that interact with the genome are being developed. The integrated biological approaches--proteomics, transcriptomics, metabolomics, and glycomics--have a strong record in several areas of biomedicine, including neurochemistry and neuro-oncology. Published applications of an integrated approach to projects of neurological, psychiatric, and pharmacological natures are still few but show promise to provide deep biological knowledge derived from cells, animal models, and clinical materials. Future studies that yield insights based on integrated analyses promise to deliver new therapeutic targets and biomarkers for personalized medicine.

Potential of zebrafish as a model for exploring the role of the amygdala in emotional memory and motivational behavior.

PubMed

Perathoner, Simon; Cordero-Maldonado, Maria Lorena; Crawford, Alexander D

2016-06-01

Emotion is a key aspect of behavior, enabling humans and animals to assign either positive or negative values to sensory inputs and thereby to make appropriate decisions. Classical experiments in mammalian models, mainly in primates and rodents, have shown that the amygdala is essential for appetitive and aversive associative processing and that dysfunction of this brain region leads to various psychiatric conditions, including depression, generalized anxiety disorder, panic disorder, phobias, autism, and posttraumatic stress disorder. In the past 2 decades, the zebrafish (Danio rerio; Cyprinidae) has emerged as a versatile, reliable vertebrate model organism for the in vivo study of development, gene function, and numerous aspects of human pathologies. Small size, high fecundity, rapid external development, transparency, genetic tractability, and high genetic and physiologic homology with humans are among the factors that have contributed to the success with this small fish in different biomedical research areas. Recent findings indicate that, despite the anatomical differences in the brain structure of teleosts and tetrapods, fish possess a structure homologous to the mammalian amygdala, a hypothesis that is supported by the expression of molecular markers, analyses of neuronal projections in different brain areas, and behavioral studies. This Review summarizes this evidence and highlights a number of relevant bioassays in zebrafish to study emotional memory and motivational behavior. © 2016 Wiley Periodicals, Inc.

Dissecting the Roles of Brain Injury and Combat-Related Stress in Post-Traumatic Headache

DTIC Science & Technology

2015-10-01

were the major goals of the project? Post-traumatic headache (PTH) is an epidemic in our military personnel. It is a chronic, migraine -like...and affective processing that lead to PTH. Cortical spreading depression (CSD) is the physiological correlate of the migraine aura, but it also...paradigm. NTG infusion triggers migraine without aura in human migraineurs and reduced mechanical allodynia threshold in rodents. This enables 11

Neuroergonomics - Analyzing Brain Function to Enhance Human Performance in Complex Systems

DTIC Science & Technology

2008-12-02

NUMBER 6. AUTHOR( S ) 5d. PROJECT NUMBER 5e. TASK NUMBER 5f. WORK UNIT NUMBER 7. PERFORMING ORGANIZATION NAME( S ) AND ADDRESS(ES) George Mason...University 8. PERFORMING ORGANIZATION REPORT NUMBER 9. SPONSORING/MONITORING AGENCY NAME( S ) AND ADDRESS(ES) 10. SPONSOR/MONITOR’S ACRONYM( S ) 11. SPONSOR...MONITOR’S REPORT NUMBER( S ) 12. DISTRIBUTION/AVAILABILITY STATEMENT Approved for public release, distribution unlimited 13. SUPPLEMENTARY NOTES See

NASA's Software Bank (NETS)

NASA Technical Reports Server (NTRS)

1992-01-01

NETS (A Neural Network Development Tool) is a software system for mimicking the human brain. It is used in a University of Arkansas project in pattern matching of chemical systems. If successful, chemists would be able to identify mixtures of compounds without long and costly separation procedures. Using NETS, the group has trained the computer to recognize pattern relationships in a known compound and associate the results to an unknown compound. The research appears to be promising.

Segmentation of the canine corpus callosum using diffusion-tensor imaging tractography.

PubMed

Pierce, Theodore T; Calabrese, Evan; White, Leonard E; Chen, Steven D; Platt, Simon R; Provenzale, James M

2014-01-01

We set out to determine functional white matter (WM) connections passing through the canine corpus callosum; these WM connections would be useful for subsequent studies of canine brains that serve as models for human WM pathway disease. Based on prior studies, we anticipated that the anterior corpus callosum would send projections to the anterior cerebral cortex whereas progressively posterior segments would send projections to more posterior cortex. A postmortem canine brain was imaged using a 7-T MRI system producing 100-μm-isotropic-resolution diffusion-tensor imaging analyzed by tractography. Using regions of interest (ROIs) within cortical locations, which were confirmed by a Nissl stain that identified distinct cortical architecture, we successfully identified six important WM pathways. We also compared fractional anisotropy (FA), apparent diffusion coefficient (ADC), radial diffusivity, and axial diffusivity in tracts passing through the genu and splenium. Callosal fibers were organized on the basis of cortical destination (e.g., fibers from the genu project to the frontal cortex). Histologic results identified the motor cortex on the basis of cytoarchitectonic criteria that allowed placement of ROIs to discriminate between frontal and parietal lobes. We also identified cytoarchitecture typical of the orbital frontal, anterior frontal, and occipital regions and placed ROIs accordingly. FA, ADC, radial diffusivity, and axial diffusivity values were all higher in posterior corpus callosum fiber tracts. Using six cortical ROIs, we identified six major WM tracts that reflect major functional divisions of the cerebral hemispheres, and we derived quantitative values that can be used for study of canine models of human WM pathologic states.

Contradictions from the enlightenment roots of transhumanism.

PubMed

Hughes, James

2010-12-01

Transhumanism, the belief that technology can transcend the limitations of the human body and brain, is part of the family of Enlightenment philosophies. As such, transhumanism has also inherited the internal tensions and contradictions of the broad Enlightenment tradition. First, the project of Reason is self-erosive and requires irrational validation. Second, although most transhumanists are atheist, their belief in the transcendent power of intelligence generates new theologies. Third, although most transhumanists are liberal democrats, their belief in human perfectibility and governance by reason can validate technocratic authoritarianism. Fourth, transhumanists are divided on the balance between democracy and the market. Fifth, teleological expectations of unstoppable progress are in tension with awareness of the indeterminacy of the future. Sixth, transhumanists are divided between advocates of ethical universalism and ethical relativism. Seventh, the rational materialist denial of discrete persistent selves calls into question the transhumanist project of individual longevity and enhancement.

The Human Connectome Project: A data acquisition perspective

PubMed Central

Van Essen, D.C.; Ugurbil, K.; Auerbach, E.; Barch, D.; Behrens, T.E.J.; Bucholz, R.; Chang, A.; Chen, L.; Corbetta, M.; Curtiss, S.W.; Della Penna, S.; Feinberg, D.; Glasser, M.F.; Harel, N.; Heath, A.C.; Larson-Prior, L.; Marcus, D.; Michalareas, G.; Moeller, S.; Oostenveld, R.; Petersen, S.E.; Prior, F.; Schlaggar, B.L.; Smith, S.M.; Snyder, A.Z.; Xu, J.; Yacoub, E.

2012-01-01

The Human Connectome Project (HCP) is an ambitious 5-year effort to characterize brain connectivity and function and their variability in healthy adults. This review summarizes the data acquisition plans being implemented by a consortium of HCP investigators who will study a population of 1200 subjects (twins and their non-twin siblings) using multiple imaging modalities along with extensive behavioral and genetic data. The imaging modalities will include diffusion imaging (dMRI), resting-state fMRI (R-fMRI), task-evoked fMRI (T-fMRI), T1- and T2-weighted MRI for structural and myelin mapping, plus combined magnetoencephalography and electroencephalography (MEG/EEG). Given the importance of obtaining the best possible data quality, we discuss the efforts underway during the first two years of the grant (Phase I) to refine and optimize many aspects of HCP data acquisition, including a new 7T scanner, a customized 3T scanner, and improved MR pulse sequences. PMID:22366334

Distinct structure and activity of monoamine oxidase in the brain of zebrafish (Danio rerio).

PubMed

Anichtchik, Oleg; Sallinen, Ville; Peitsaro, Nina; Panula, Pertti

2006-10-10

Monoamine oxidase (MAO) is a mitochondrial flavoprotein involved in the metabolism of, e.g., aminergic neurotransmitters and the parkinsonism-inducing neurotoxin 1-methyl-4-phenyl-1,2,5,6-tetrahydropyridine (MPTP). We have reported earlier MPTP-related alterations of brain catecholaminergic system in zebrafish (Danio rerio) brain. Here we describe the structural and functional properties of zebrafish MAO and the distribution of MAO mRNA and activity in zebrafish brain. The gene is located in chromosome 9 and consists of 15 exons. The amino acid composition of the active center resembles both human MAO-A and MAO-B. The enzyme displayed the highest substrate specificity for tyramine, followed by serotonin, phenylethylamine, MPTP, and dopamine; isoform-specific antagonists blocked the activity of the enzyme with equal potency. Zebrafish MAO mRNA, which was present in several tissues, and enzyme displayed differential distribution in the brain; dopaminergic cell clusters had low to moderate levels of MAO activity, whereas the highest levels of MAO activity were detected in noradrenergic and serotonergic cell groups and the habenulointerpeduncular pathway, including its caudal projection to the medial ventral rhombencephalon. The results of this study confirm the presence of functionally active MAO in zebrafish brain and other tissues and characterize the neural systems that express MAO and areas of intense activity in the brain. They also suggest that MPTP toxicity not related to MAO may affect the zebrafish brain.

An in vivo model of functional and vascularized human brain organoids.

PubMed

Mansour, Abed AlFatah; Gonçalves, J Tiago; Bloyd, Cooper W; Li, Hao; Fernandes, Sarah; Quang, Daphne; Johnston, Stephen; Parylak, Sarah L; Jin, Xin; Gage, Fred H

2018-06-01

Differentiation of human pluripotent stem cells to small brain-like structures known as brain organoids offers an unprecedented opportunity to model human brain development and disease. To provide a vascularized and functional in vivo model of brain organoids, we established a method for transplanting human brain organoids into the adult mouse brain. Organoid grafts showed progressive neuronal differentiation and maturation, gliogenesis, integration of microglia, and growth of axons to multiple regions of the host brain. In vivo two-photon imaging demonstrated functional neuronal networks and blood vessels in the grafts. Finally, in vivo extracellular recording combined with optogenetics revealed intragraft neuronal activity and suggested graft-to-host functional synaptic connectivity. This combination of human neural organoids and an in vivo physiological environment in the animal brain may facilitate disease modeling under physiological conditions.

78 FR 27198 - Applications for New Awards; National Institute on Disability and Rehabilitation Research...

Federal Register 2010, 2011, 2012, 2013, 2014

2013-05-09

... Rehabilitation Research--Traumatic Brain Injury Model Systems Centers Collaborative Research Project AGENCY... Brain Injury Model Systems Centers Collaborative Research Projects; Notice inviting applications for new... competition. Priority 1, the DRRP Priority for the Traumatic Brain Injury Model Systems Centers Collaborative...

Inferring Selective Constraint from Population Genomic Data Suggests Recent Regulatory Turnover in the Human Brain

PubMed Central

Schrider, Daniel R.; Kern, Andrew D.

2015-01-01

The comparative genomics revolution of the past decade has enabled the discovery of functional elements in the human genome via sequence comparison. While that is so, an important class of elements, those specific to humans, is entirely missed by searching for sequence conservation across species. Here we present an analysis based on variation data among human genomes that utilizes a supervised machine learning approach for the identification of human-specific purifying selection in the genome. Using only allele frequency information from the complete low-coverage 1000 Genomes Project data set in conjunction with a support vector machine trained from known functional and nonfunctional portions of the genome, we are able to accurately identify portions of the genome constrained by purifying selection. Our method identifies previously known human-specific gains or losses of function and uncovers many novel candidates. Candidate targets for gain and loss of function along the human lineage include numerous putative regulatory regions of genes essential for normal development of the central nervous system, including a significant enrichment of gain of function events near neurotransmitter receptor genes. These results are consistent with regulatory turnover being a key mechanism in the evolution of human-specific characteristics of brain development. Finally, we show that the majority of the genome is unconstrained by natural selection currently, in agreement with what has been estimated from phylogenetic methods but in sharp contrast to estimates based on transcriptomics or other high-throughput functional methods. PMID:26590212

Cumulative role of rare and common putative functional genetic variants at NPAS3 in schizophrenia susceptibility.

PubMed

González-Peñas, Javier; Arrojo, Manuel; Paz, Eduardo; Brenlla, Julio; Páramo, Mario; Costas, Javier

2015-10-01

Schizophrenia may be considered a human-specific disorder arisen as a maladaptive by-product of human-specific brain evolution. Therefore, genetic variants involved in susceptibility to schizophrenia may be identified among those genes related to acquisition of human-specific traits. NPAS3, a transcription factor involved in central nervous system development and neurogenesis, seems to be implicated in the evolution of human brain, as it is the human gene with most human-specific accelerated elements (HAEs), i.e., .mammalian conserved regulatory sequences with accelerated evolution in the lineage leading to humans after human-chimpanzee split. We hypothesize that any nucleotide variant at the NPAS3 HAEs may lead to altered susceptibility to schizophrenia. Twenty-one variants at these HAEs detected by the 1000 genomes Project, as well as five additional variants taken from psychiatric genome-wide association studies, were genotyped in 538 schizophrenic patients and 539 controls from Galicia. Analyses at the haplotype level or based on the cumulative role of the variants assuming different susceptibility models did not find any significant association in spite of enough power under several plausible scenarios regarding direction of effect and the specific role of rare and common variants. These results suggest that, contrary to our hypothesis, the special evolution of the NPAS3 HAEs in Homo relaxed the strong constraint on sequence that characterized these regions during mammalian evolution, allowing some sequence changes without any effect on schizophrenia risk. © 2015 Wiley Periodicals, Inc.

Optimal Control of Inspired Perfluorocarbon Temperature for Ultrafast Hypothermia Induction by Total Liquid Ventilation in an Adult Patient Model.

PubMed

Nadeau, Mathieu; Sage, Michael; Kohlhauer, Matthias; Mousseau, Julien; Vandamme, Jonathan; Fortin-Pellerin, Etienne; Praud, Jean-Paul; Tissier, Renaud; Walti, Herve; Micheau, Philippe

2017-12-01

Recent preclinical studies have shown that therapeutic hypothermia induced in less than 30 min by total liquid ventilation (TLV) strongly improves the survival rate after cardiac arrest. When the lung is ventilated with a breathable perfluorocarbon liquid, the inspired perfluorocarbon allows us to control efficiently the cooling process of the organs. While TLV can rapidly cool animals, the cooling speed in humans remains unknown. The objective is to predict the efficiency and safety of ultrafast cooling by TLV in adult humans. It is based on a previously published thermal model of ovines in TLV and the design of a direct optimal controller to compute the inspired perfluorocarbon temperature profile. The experimental results in an adult sheep are presented. The thermal model of sheep is subsequently projected to a human model to simulate the optimal hypothermia induction and its sensitivity to physiological parameter uncertainties. The results in the sheep showed that the computed inspired perfluorocarbon temperature command can avoid arterial temperature undershoot. The projection to humans revealed that mild hypothermia should be ultrafast (reached in fewer than 3 min (-72 °C/h) for the brain and 20 min (-10 °C/h) for the entire body). The projection to human model allows concluding that therapeutic hypothermia induction by TLV can be ultrafast and safe. This study is the first to simulate ultrafast cooling by TLV in a human model and is a strong motivation to translate TLV to humans to improve the quality of life of postcardiac arrest patients.

Multitarget drug discovery projects in CNS diseases: quantitative systems pharmacology as a possible path forward.

PubMed

Geerts, Hugo; Kennis, Ludo

2014-01-01

Clinical development in brain diseases has one of the lowest success rates in the pharmaceutical industry, and many promising rationally designed single-target R&D projects fail in expensive Phase III trials. By contrast, successful older CNS drugs do have a rich pharmacology. This article will provide arguments suggesting that highly selective single-target drugs are not sufficiently powerful to restore complex neuronal circuit homeostasis. A rationally designed multitarget project can be derisked by dialing in an additional symptomatic treatment effect on top of a disease modification target. Alternatively, we expand upon a hypothetical workflow example using a humanized computer-based quantitative systems pharmacology platform. The hope is that incorporating rationally multipharmacology drug discovery could potentially lead to more impactful polypharmacy drugs.

iELVis: An open source MATLAB toolbox for localizing and visualizing human intracranial electrode data.

PubMed

Groppe, David M; Bickel, Stephan; Dykstra, Andrew R; Wang, Xiuyuan; Mégevand, Pierre; Mercier, Manuel R; Lado, Fred A; Mehta, Ashesh D; Honey, Christopher J

2017-04-01

Intracranial electrical recordings (iEEG) and brain stimulation (iEBS) are invaluable human neuroscience methodologies. However, the value of such data is often unrealized as many laboratories lack tools for localizing electrodes relative to anatomy. To remedy this, we have developed a MATLAB toolbox for intracranial electrode localization and visualization, iELVis. NEW METHOD: iELVis uses existing tools (BioImage Suite, FSL, and FreeSurfer) for preimplant magnetic resonance imaging (MRI) segmentation, neuroimaging coregistration, and manual identification of electrodes in postimplant neuroimaging. Subsequently, iELVis implements methods for correcting electrode locations for postimplant brain shift with millimeter-scale accuracy and provides interactive visualization on 3D surfaces or in 2D slices with optional functional neuroimaging overlays. iELVis also localizes electrodes relative to FreeSurfer-based atlases and can combine data across subjects via the FreeSurfer average brain. It takes 30-60min of user time and 12-24h of computer time to localize and visualize electrodes from one brain. We demonstrate iELVis's functionality by showing that three methods for mapping primary hand somatosensory cortex (iEEG, iEBS, and functional MRI) provide highly concordant results. COMPARISON WITH EXISTING METHODS: iELVis is the first public software for electrode localization that corrects for brain shift, maps electrodes to an average brain, and supports neuroimaging overlays. Moreover, its interactive visualizations are powerful and its tutorial material is extensive. iELVis promises to speed the progress and enhance the robustness of intracranial electrode research. The software and extensive tutorial materials are freely available as part of the EpiSurg software project: https://github.com/episurg/episurg. Copyright © 2017 Elsevier B.V. All rights reserved.

The MNESIS model: Memory systems and processes, identity and future thinking.

PubMed

Eustache, Francis; Viard, Armelle; Desgranges, Béatrice

2016-07-01

The Memory NEo-Structural Inter-Systemic model (MNESIS; Eustache and Desgranges, Neuropsychology Review, 2008) is a macromodel based on neuropsychological data which presents an interactive construction of memory systems and processes. Largely inspired by Tulving's SPI model, MNESIS puts the emphasis on the existence of different memory systems in humans and their reciprocal relations, adding new aspects, such as the episodic buffer proposed by Baddeley. The more integrative comprehension of brain dynamics offered by neuroimaging has contributed to rethinking the existence of memory systems. In the present article, we will argue that understanding the concept of memory by dividing it into systems at the functional level is still valid, but needs to be considered in the light of brain imaging. Here, we reinstate the importance of this division in different memory systems and illustrate, with neuroimaging findings, the links that operate between memory systems in response to task demands that constrain the brain dynamics. During a cognitive task, these memory systems interact transiently to rapidly assemble representations and mobilize functions to propose a flexible and adaptative response. We will concentrate on two memory systems, episodic and semantic memory, and their links with autobiographical memory. More precisely, we will focus on interactions between episodic and semantic memory systems in support of 1) self-identity in healthy aging and in brain pathologies and 2) the concept of the prospective brain during future projection. In conclusion, this MNESIS global framework may help to get a general representation of human memory and its brain implementation with its specific components which are in constant interaction during cognitive processes. Copyright © 2016 Elsevier Ltd. All rights reserved.

Effects of One Year of Spaceflight on Neurocognitive Function

NASA Technical Reports Server (NTRS)

Seidler, R. D.; Mulavara, A. P.; Koppelmans, V.; Kofman, I. S.; Cassady, K.; Yuan , P.; De Dios, Y. E.; Gadd, N.; Riascos, R. F.; Wood, S. J.;

Vasopressin: Behavioral Roles of an “Original” Neuropeptide

PubMed Central

Caldwell, Heather K.; Lee, Heon-Jin; Macbeth, Abbe H.; Young, W. Scott

2008-01-01

Vasopressin (Avp) is mainly synthesized in the magnocellular cells of the hypothalamic supraoptic (SON) and paraventricular nuclei (PVN) whose axons project to the posterior pituitary. Avp is then released into the blood stream upon appropriate stimulation (e.g., hemorrhage or dehydration) to act at the kidneys and blood vessels. The brain also contains several populations of smaller, parvocellular neurons whose projections remain within the brain. These populations are located within the PVN, bed nucleus of the stria terminalis (BNST), medial amygdala (MeA) and suprachiasmatic nucleus (SCN). Since the 1950's, research examining the roles of Avp in the brain and periphery has intensified. The development of specific agonists and antagonists for Avp receptors has allowed for a better elucidation of its contributions to physiology and behavior. Anatomical, pharmacological and transgenic, including “knockout,” animal studies, have implicated Avp in the regulation of various social behaviors across species. Avp plays a prominent role in the regulation of aggression, generally of facilitating or promoting it. Affiliation and certain aspects of pair-bonding are also influenced by Avp. Memory, one of the first brain functions of Avp that was investigated, has been implicated especially strongly in social recognition. The roles of Avp in stress, anxiety, and depressive states are areas of active exploration. In this review, we concentrate on the scientific progress that has been made on understanding the role of Avp in regulating of these and other behaviors across species, as well as discuss the implications for human behavior. PMID:18053631

Structural and molecular interrogation of intact biological systems

PubMed Central

Chung, Kwanghun; Wallace, Jenelle; Kim, Sung-Yon; Kalyanasundaram, Sandhiya; Andalman, Aaron S.; Davidson, Thomas J.; Mirzabekov, Julie J.; Zalocusky, Kelly A.; Mattis, Joanna; Denisin, Aleksandra K.; Pak, Sally; Bernstein, Hannah; Ramakrishnan, Charu; Grosenick, Logan; Gradinaru, Viviana; Deisseroth, Karl

2014-01-01

Obtaining high-resolution information from a complex system, while maintaining the global perspective needed to understand system function, represents a key challenge in biology. Here we address this challenge with a method (termed CLARITY) for the transformation of intact tissue into a nanoporous hydrogel-hybridized form (crosslinked to a three-dimensional network of hydrophilic polymers) that is fully assembled but optically transparent and macromolecule-permeable. Using mouse brains, we show intact-tissue imaging of long-range projections, local circuit wiring, cellular relationships, subcellular structures, protein complexes, nucleic acids and neurotransmitters. CLARITY also enables intact-tissue in situ hybridization, immunohistochemistry with multiple rounds of staining and de-staining in non-sectioned tissue, and antibody labelling throughout the intact adult mouse brain. Finally, we show that CLARITY enables fine structural analysis of clinical samples, including non-sectioned human tissue from a neuropsychiatric-disease setting, establishing a path for the transmutation of human tissue into a stable, intact and accessible form suitable for probing structural and molecular underpinnings of physiological function and disease. PMID:23575631

Regional selection of the brain size regulating gene CASC5 provides new insight into human brain evolution.

PubMed

Shi, Lei; Hu, Enzhi; Wang, Zhenbo; Liu, Jiewei; Li, Jin; Li, Ming; Chen, Hua; Yu, Chunshui; Jiang, Tianzi; Su, Bing

2017-02-01

Human evolution is marked by a continued enlargement of the brain. Previous studies on human brain evolution focused on identifying sequence divergences of brain size regulating genes between humans and nonhuman primates. However, the evolutionary pattern of the brain size regulating genes during recent human evolution is largely unknown. We conducted a comprehensive analysis of the brain size regulating gene CASC5 and found that in recent human evolution, CASC5 has accumulated many modern human specific amino acid changes, including two fixed changes and six polymorphic changes. Among human populations, 4 of the 6 amino acid polymorphic sites have high frequencies of derived alleles in East Asians, but are rare in Europeans and Africans. We proved that this between-population allelic divergence was caused by regional Darwinian positive selection in East Asians. Further analysis of brain image data of Han Chinese showed significant associations of the amino acid polymorphic sites with gray matter volume. Hence, CASC5 may contribute to the morphological and structural changes of the human brain during recent evolution. The observed between-population divergence of CASC5 variants was driven by natural selection that tends to favor a larger gray matter volume in East Asians.

General, crystallized and fluid intelligence are not associated with functional global network efficiency: A replication study with the human connectome project 1200 data set.

PubMed

Kruschwitz, J D; Waller, L; Daedelow, L S; Walter, H; Veer, I M

2018-05-01

One hallmark example of a link between global topological network properties of complex functional brain connectivity and cognitive performance is the finding that general intelligence may depend on the efficiency of the brain's intrinsic functional network architecture. However, although this association has been featured prominently over the course of the last decade, the empirical basis for this broad association of general intelligence and global functional network efficiency is quite limited. In the current study, we set out to replicate the previously reported association between general intelligence and global functional network efficiency using the large sample size and high quality data of the Human Connectome Project, and extended the original study by testing for separate association of crystallized and fluid intelligence with global efficiency, characteristic path length, and global clustering coefficient. We were unable to provide evidence for the proposed association between general intelligence and functional brain network efficiency, as was demonstrated by van den Heuvel et al. (2009), or for any other association with the global network measures employed. More specifically, across multiple network definition schemes, ranging from voxel-level networks to networks of only 100 nodes, no robust associations and only very weak non-significant effects with a maximal R 2 of 0.01 could be observed. Notably, the strongest (non-significant) effects were observed in voxel-level networks. We discuss the possibility that the low power of previous studies and publication bias may have led to false positive results fostering the widely accepted notion of general intelligence being associated to functional global network efficiency. Copyright © 2018 Elsevier Inc. All rights reserved.

Distribution of language-related Cntnap2 protein in neural circuits critical for vocal learning.

PubMed

Condro, Michael C; White, Stephanie A

2014-01-01

Variants of the contactin associated protein-like 2 (Cntnap2) gene are risk factors for language-related disorders including autism spectrum disorder, specific language impairment, and stuttering. Songbirds are useful models for study of human speech disorders due to their shared capacity for vocal learning, which relies on similar cortico-basal ganglia circuitry and genetic factors. Here we investigate Cntnap2 protein expression in the brain of the zebra finch, a songbird species in which males, but not females, learn their courtship songs. We hypothesize that Cntnap2 has overlapping functions in vocal learning species, and expect to find protein expression in song-related areas of the zebra finch brain. We further expect that the distribution of this membrane-bound protein may not completely mirror its mRNA distribution due to the distinct subcellular localization of the two molecular species. We find that Cntnap2 protein is enriched in several song control regions relative to surrounding tissues, particularly within the adult male, but not female, robust nucleus of the arcopallium (RA), a cortical song control region analogous to human layer 5 primary motor cortex. The onset of this sexually dimorphic expression coincides with the onset of sensorimotor learning in developing males. Enrichment in male RA appears due to expression in projection neurons within the nucleus, as well as to additional expression in nerve terminals of cortical projections to RA from the lateral magnocellular nucleus of the nidopallium. Cntnap2 protein expression in zebra finch brain supports the hypothesis that this molecule affects neural connectivity critical for vocal learning across taxonomic classes. Copyright © 2013 Wiley Periodicals, Inc.

The connectomics challenge

PubMed Central

Silvestri, Ludovico; Sacconi, Leonardo; Pavone, Francesco Saverio

Summary One of the most fascinating challenges in neuroscience is the reconstruction of the connectivity map of the brain. Recent years have seen a rapid expansion in the field of connectomics, whose aim is to trace this map and understand its relationship with neural computation. Many different approaches, ranging from electron and optical microscopy to magnetic resonance imaging, have been proposed to address the connectomics challenge on various spatial scales and in different species. Here, we review the main technological advances in the microscopy techniques applied to connectomics, highlighting the potential and limitations of the different methods. Finally, we briefly discuss the role of connectomics in the Human Brain Project, the Future and Emerging Technologies (FET) Flagship recently approved by the European Commission. PMID:24139653

Methods for studying the zebrafish brain: past, present and future.

PubMed

Wyatt, Cameron; Bartoszek, Ewelina M; Yaksi, Emre

2015-07-01

The zebrafish (Danio rerio) is one of the most promising new model organisms. The increasing popularity of this amazing small vertebrate is evident from the exponentially growing numbers of research articles, funded projects and new discoveries associated with the use of zebrafish for studying development, brain function, human diseases and screening for new drugs. Thanks to the development of novel technologies, the range of zebrafish research is constantly expanding with new tools synergistically enhancing traditional techniques. In this review we will highlight the past and present techniques which have made, and continue to make, zebrafish an attractive model organism for various fields of biology, with a specific focus on neuroscience. © 2015 Federation of European Neuroscience Societies and John Wiley & Sons Ltd.

Accelerated recruitment of new brain development genes into the human genome.

PubMed

Zhang, Yong E; Landback, Patrick; Vibranovski, Maria D; Long, Manyuan

2011-10-01

How the human brain evolved has attracted tremendous interests for decades. Motivated by case studies of primate-specific genes implicated in brain function, we examined whether or not the young genes, those emerging genome-wide in the lineages specific to the primates or rodents, showed distinct spatial and temporal patterns of transcription compared to old genes, which had existed before primate and rodent split. We found consistent patterns across different sources of expression data: there is a significantly larger proportion of young genes expressed in the fetal or infant brain of humans than in mouse, and more young genes in humans have expression biased toward early developing brains than old genes. Most of these young genes are expressed in the evolutionarily newest part of human brain, the neocortex. Remarkably, we also identified a number of human-specific genes which are expressed in the prefrontal cortex, which is implicated in complex cognitive behaviors. The young genes upregulated in the early developing human brain play diverse functional roles, with a significant enrichment of transcription factors. Genes originating from different mechanisms show a similar expression bias in the developing brain. Moreover, we found that the young genes upregulated in early brain development showed rapid protein evolution compared to old genes also expressed in the fetal brain. Strikingly, genes expressed in the neocortex arose soon after its morphological origin. These four lines of evidence suggest that positive selection for brain function may have contributed to the origination of young genes expressed in the developing brain. These data demonstrate a striking recruitment of new genes into the early development of the human brain.

Methods and Management of the Healthy Brain Study: A Large Multisite Qualitative Research Project

ERIC Educational Resources Information Center

Laditka, Sarah B.; Corwin, Sara J.; Laditka, James N.; Liu, Rui; Friedman, Daniela B.; Mathews, Anna E.; Wilcox, Sara

2009-01-01

Purpose of the study: To describe processes used in the Healthy Brain project to manage data collection, coding, and data distribution in a large qualitative project, conducted by researchers at 9 universities in 9 states. Design and Methods: Project management protocols included: (a) managing audiotapes and surveys to ensure data confidentiality,…

Structural development of human brain white matter from mid-fetal to perinatal stage

NASA Astrophysics Data System (ADS)

Ouyang, Austin; Yu, Qiaowen; Mishra, Virendra; Chalak, Lina; Jeon, Tina; Sivarajan, Muraleedharan; Jackson, Greg; Rollins, Nancy; Liu, Shuwei; Huang, Hao

2015-03-01

The structures of developing human brain white matter (WM) tracts can be effectively quantified by DTI-derived metrics, including fractional anisotropy (FA), mean, axial and radial diffusivity (MD, AD and RD). However, dynamics of WM microstructure during very early developmental period from mid-fetal to perinatal stage is unknown. It is difficult to accurately measure microstructural properties of these WM tracts due to severe contamination from cerebrospinal fluid (CSF). In this study, high resolution DTI of fetal brains at mid-fetal stage (20 weeks of gestation or 20wg), 19 brains in the middle of 3rd trimester (35wg) and 17 brains around term (40wg) were acquired. We established first population-averaged DTI templates at these three time points and extracted WM skeleton. 16 major WM tracts in limbic, projection, commissural and association tract groups were traced with DTI tractography in native space. The WM skeleton in the template space was inversely transformed back to the native space for measuring core WM microstructures of each individual tract. Continuous microstructural enhancement and volumetric increase of WM tracts were found from 20wg to 40wg. The microstructural enhancement from FA measurement is decelerated in late 3rd trimester compared to mid-fetal to middle 3rd trimester, while volumetric increase of prefrontal WM tracts is accelerated. The microstructural enhancement from 35wg to 40wg is heterogeneous among different tract groups with microstructures of association tracts undergoing most dramatic change. Besides decreases of RD indicating active myelination, the decrease of AD for most WM tracts during late 3rd trimester suggests axonal packing process.

Hand grips strength effect on motor function in human brain using fMRI: a pilot study

NASA Astrophysics Data System (ADS)

Ismail, S. S.; Mohamad, M.; Syazarina, S. O.; Nafisah, W. Y.

2014-11-01

Several methods of motor tasks for fMRI scanning have been evolving from simple to more complex tasks. Motor tasks on upper extremity were applied in order to excite the increscent of motor activation on contralesional and ipsilateral hemispheres in brain. The main objective of this study is to study the different conditions for motor tasks on upper extremity that affected the brain activation. Ten healthy right handed with normal vision (3 male and 7 female, age range=20-30 years, mean=24.6 years, SD=2.21) participated in this study. Prior to the scanning, participants were trained on hand grip tasks using rubber ball and pressure gauge tool outside the scanner. During fMRI session, a block design with 30-s task blocks and alternating 30-s rest periods was employed while participants viewed a computer screen via a back projection-mirror system and instructed to follow the instruction by gripping their hand with normal and strong grips using a rubber ball. Statistical Parametric mapping (SPM8) software was used to determine the brain activation. Both tasks activated the primary motor (M1), supplementary motor area (SMA), dorsal and ventral of premotor cortex area (PMA) in left hemisphere while in right hemisphere the area of primary motor (M1) somatosensory was activated. However, the comparison between both tasks revealed that the strong hand grip showed the higher activation at M1, PMA and SMA on left hemisphere and also the area of SMA on right hemisphere. Both conditions of motor tasks could provide insights the functional organization on human brain.

Coping with Brain Disorders using Neurotechnology.

PubMed

Pedro A, Valdes-Sosa

2012-01-01

Brain disorders account for more than 34% of the global burden of disease, crippling nations by decreasing their "mental capital"-with greater effect in developing countries. Early detection is the key to their management, but establishing such programmes seems nearly impossible due to the high prevalence of the dysfunctions as compared with the high cost of neuroimaging devices. Thus, at first sight, the research of the Decade of the Brain and the international Human Brain Mapping Project might seem to be condemned to benefit only a small elite. Cuba has shown that is not so by using neurotechnology for the last 3 decades to implement stratified active screening programmes for brain disorders at the population level. This experience has shown that, by the transformation of health indicators, an appropriate use of technology can be integrated with attention to the population at the primary levels of both health care and education. An essential component of neurotechnology is neuroinformatics, which-like its counterpart bioinformatics-combines databases, analysis tools, and theoretical models to craft tools for early disease diagnosis and management. Much work remains to be done and will depend critically on south-south cooperation to solve problems for countries with similar situations.

Coping with Brain Disorders using Neurotechnology

PubMed Central

Pedro A, Valdes-Sosa

2012-01-01

Brain disorders account for more than 34% of the global burden of disease, crippling nations by decreasing their “mental capital”—with greater effect in developing countries. Early detection is the key to their management, but establishing such programmes seems nearly impossible due to the high prevalence of the dysfunctions as compared with the high cost of neuroimaging devices. Thus, at first sight, the research of the Decade of the Brain and the international Human Brain Mapping Project might seem to be condemned to benefit only a small elite. Cuba has shown that is not so by using neurotechnology for the last 3 decades to implement stratified active screening programmes for brain disorders at the population level. This experience has shown that, by the transformation of health indicators, an appropriate use of technology can be integrated with attention to the population at the primary levels of both health care and education. An essential component of neurotechnology is neuroinformatics, which—like its counterpart bioinformatics—combines databases, analysis tools, and theoretical models to craft tools for early disease diagnosis and management. Much work remains to be done and will depend critically on south—south cooperation to solve problems for countries with similar situations. PMID:22977368

Consensus document on European brain research.

PubMed

Olesen, Jes; Baker, Mary G; Freund, Tamas; di Luca, Monica; Mendlewicz, Julien; Ragan, Ian; Westphal, Manfred

2006-08-01

Brain disease psychiatric and neurologic disease combined represents a considerable social and economic burden in Europe. Data collected by the World Health Organization (WHO) suggest that brain diseases are responsible for 35% of Europe's total disease burden. An analysis of all health economic studies of brain diseases in Europe, published by the European Brain Council (EBC) in June 2005, estimated the total cost of brain disease in Europe in 2004 to be Euro 386 billion. That burden is set to grow, mainly due to the fact that the European population is ageing. Investment in brain sciences does not match that burden now, let alone in the future. Brain research received only 8% of the life science budget in the European Commission's Fifth Framework Programme, which represents less than 0.01% of the annual cost of brain disorders for that period. Over the last decade, Europe has been losing ground to the USA and Japan in terms of both basic and clinical research. Many of Europe's young researchers are taking up posts in the USA and staying there. Big pharmaceutical companies are fleeing Europe for the USA, taking their drug development programmes with them. Research in the brain sciences now holds the promise of therapies that halt and even reverse neurodegeneration, of better diagnostic tools, neural prostheses for the paralysed and drugs for depression and anxiety that are tailored to the individual, thereby eliminating or reducing side effects. Our growing understanding of the normal brain could lead to better prevention of brain disease and to more effective teaching methods. The need for innovative treatments has never been greater, and Europe boasts clusters of excellent researchers in biotechnology who could collaborate with brain scientists and the pharmaceutical industry to realise this promise. But if Europe is to seize these opportunities and meet the challenge of brain disease, it needs to go forward on the basis of greater collaboration between countries, greater collaboration between industry, academia and patient organisations, and increased investment in the brain sciences. The EBC was formed in 2002 to bring together scientists, clinicians, the pharmaceutical industry, charities and patient organisations from all over Europe to campaign for these goals. It takes a novel, bottom-up approach to research policy, and in developing this consensus document, it aims to promote a greater and more focused effort in this area, to improve public understanding of the brain sciences and above all, to support brain research as a priority under the European Commission's Seventh Framework Programme (FP7, 2007-2013). The research programme outlined here was first conceived by the EBC board. An outline was sent to all member organisations and a number of individual experts for comments. Following that, a table of contents was developed. The 45 research themes were written by groups of experts from across Europe who represent a wide range of disciplines. Each one contains a proposal for future research on a specific brain-related theme which the EBC believes could form the basis of one or more integrated projects or strategic targeted research projects (STREP) funded under FP7. The EBC has deliberately focused on the major diseases and then described the basic research needed to understand and treat or perhaps even cure those diseases. The programme is therefore constructed "from man to molecule" and not the other way round, with equal importance attached to basic and clinical research. The EBC suggests that each of the proposed integrated projects or STREP should be awarded a budget in the order of Euro 10 to 15 million. In addition, brain research should be treated as an important element of many other parts of FP7, such as the European Research Council and research programmes on information technology and the causes of violence. Any research programme that concerns human behaviour should, by definition, take account of brain research. The EBC envisages that the priority for brain research it proposes at the European level will translate into higher priority for brain research at the national level, and this document may also serve as a starting point for the development of national consensus programmes. It seems likely that consensus conferences on brain research in Europe may further develop the themes and ideas discussed here. An EBC task force may also be established to further the consensus process. In general, increasing funding in the brain sciences would bring enormous economic returns by lightening the burden on healthcare systems and increasing the productivity of affected individuals-and might easily pay for itself. The human and social returns of such an investment are inestimable. And the time to act is now.

Tractography optimization using quantitative T1 mapping in the human optic radiation.

PubMed

Schurr, Roey; Duan, Yiran; Norcia, Anthony M; Ogawa, Shumpei; Yeatman, Jason D; Mezer, Aviv A

2018-06-21

Diffusion MRI tractography is essential for reconstructing white-matter projections in the living human brain. Yet tractography results miss some projections and falsely identify others. A challenging example is the optic radiation (OR) that connects the thalamus and the primary visual cortex. Here, we tested whether OR tractography can be optimized using quantitative T1 mapping. Based on histology, we proposed that myelin-sensitive T1 values along the OR should remain consistently low compared with adjacent white matter. We found that complementary information from the T1 map allows for increasing the specificity of the reconstructed OR tract by eliminating falsely identified projections. This T1-filtering outperforms other, diffusion-based tractography filters. These results provide evidence that the smooth microstructural signature along the tract can be used as constructive input for tractography. Finally, we demonstrate that this approach can be generalized to the HCP-available MRI measurements. We conclude that multimodal MRI microstructural information can be used to eliminate spurious tractography results in the case of the OR. Copyright © 2018. Published by Elsevier Inc.

The brain-life theory: towards a consistent biological definition of humanness.

PubMed Central

Goldenring, J M

1985-01-01

This paper suggests that medically the term a 'human being' should be defined by the presence of an active human brain. The brain is the only unique and irreplaceable organ in the human body, as the orchestrator of all organ systems and the seat of personality. Thus, the presence or absence of brain life truly defines the presence or absence of human life in the medical sense. When viewed in this way, human life may be seen as a continuous spectrum between the onset of brain life in utero (eight weeks gestation), until the occurrence of brain death. At any point human tissue or organ systems may be present, but without the presence of a functional human brain, these do not constitute a 'human being', at least in a medical sense. The implications of this theory for various ethical concerns such as in vitro fertilisation and abortion are discussed. This theory is the most consistent possible for the definition of a human being with no contradictions inherent. However, having a good theory of definition of a 'human being' does not necessarily solve the ethical problems discussed herein. PMID:4078859

ATPP: A Pipeline for Automatic Tractography-Based Brain Parcellation

PubMed Central

Li, Hai; Fan, Lingzhong; Zhuo, Junjie; Wang, Jiaojian; Zhang, Yu; Yang, Zhengyi; Jiang, Tianzi

2017-01-01

There is a longstanding effort to parcellate brain into areas based on micro-structural, macro-structural, or connectional features, forming various brain atlases. Among them, connectivity-based parcellation gains much emphasis, especially with the considerable progress of multimodal magnetic resonance imaging in the past two decades. The Brainnetome Atlas published recently is such an atlas that follows the framework of connectivity-based parcellation. However, in the construction of the atlas, the deluge of high resolution multimodal MRI data and time-consuming computation poses challenges and there is still short of publically available tools dedicated to parcellation. In this paper, we present an integrated open source pipeline (https://www.nitrc.org/projects/atpp), named Automatic Tractography-based Parcellation Pipeline (ATPP) to realize the framework of parcellation with automatic processing and massive parallel computing. ATPP is developed to have a powerful and flexible command line version, taking multiple regions of interest as input, as well as a user-friendly graphical user interface version for parcellating single region of interest. We demonstrate the two versions by parcellating two brain regions, left precentral gyrus and middle frontal gyrus, on two independent datasets. In addition, ATPP has been successfully utilized and fully validated in a variety of brain regions and the human Brainnetome Atlas, showing the capacity to greatly facilitate brain parcellation. PMID:28611620

77 FR 34359 - Applications for New Awards: Disability and Rehabilitation Research Projects and Centers Program...

Federal Register 2010, 2011, 2012, 2013, 2014

2012-06-11

... Projects and Centers Program; Traumatic Brain Injury Model Systems Centers AGENCY: Office of Special... Brain Injury Model Systems Centers (TBIMS). Notice inviting applications for new awards for fiscal year... 28, 2006 (71 FR 25472). The Traumatic Brain Injury Model Systems Centers priority is from the notice...

Gorilla and Orangutan Brains Conform to the Primate Cellular Scaling Rules: Implications for Human Evolution

PubMed Central

Herculano-Houzel, Suzana; Kaas, Jon H.

2011-01-01

Gorillas and orangutans are primates at least as large as humans, but their brains amount to about one third of the size of the human brain. This discrepancy has been used as evidence that the human brain is about 3 times larger than it should be for a primate species of its body size. In contrast to the view that the human brain is special in its size, we have suggested that it is the great apes that might have evolved bodies that are unusually large, on the basis of our recent finding that the cellular composition of the human brain matches that expected for a primate brain of its size, making the human brain a linearly scaled-up primate brain in its number of cells. To investigate whether the brain of great apes also conforms to the primate cellular scaling rules identified previously, we determine the numbers of neuronal and other cells that compose the orangutan and gorilla cerebella, use these numbers to calculate the size of the brain and of the cerebral cortex expected for these species, and show that these match the sizes described in the literature. Our results suggest that the brains of great apes also scale linearly in their numbers of neurons like other primate brains, including humans. The conformity of great apes and humans to the linear cellular scaling rules that apply to other primates that diverged earlier in primate evolution indicates that prehistoric Homo species as well as other hominins must have had brains that conformed to the same scaling rules, irrespective of their body size. We then used those scaling rules and published estimated brain volumes for various hominin species to predict the numbers of neurons that composed their brains. We predict that Homo heidelbergensis and Homo neanderthalensis had brains with approximately 80 billion neurons, within the range of variation found in modern Homo sapiens. We propose that while the cellular scaling rules that apply to the primate brain have remained stable in hominin evolution (since they apply to simians, great apes and modern humans alike), the Colobinae and Pongidae lineages favored marked increases in body size rather than brain size from the common ancestor with the Homo lineage, while the Homo lineage seems to have favored a large brain instead of a large body, possibly due to the metabolic limitations to having both. PMID:21228547

Gorilla and orangutan brains conform to the primate cellular scaling rules: implications for human evolution.

PubMed

Herculano-Houzel, Suzana; Kaas, Jon H

2011-01-01

Gorillas and orangutans are primates at least as large as humans, but their brains amount to about one third of the size of the human brain. This discrepancy has been used as evidence that the human brain is about 3 times larger than it should be for a primate species of its body size. In contrast to the view that the human brain is special in its size, we have suggested that it is the great apes that might have evolved bodies that are unusually large, on the basis of our recent finding that the cellular composition of the human brain matches that expected for a primate brain of its size, making the human brain a linearly scaled-up primate brain in its number of cells. To investigate whether the brain of great apes also conforms to the primate cellular scaling rules identified previously, we determine the numbers of neuronal and other cells that compose the orangutan and gorilla cerebella, use these numbers to calculate the size of the brain and of the cerebral cortex expected for these species, and show that these match the sizes described in the literature. Our results suggest that the brains of great apes also scale linearly in their numbers of neurons like other primate brains, including humans. The conformity of great apes and humans to the linear cellular scaling rules that apply to other primates that diverged earlier in primate evolution indicates that prehistoric Homo species as well as other hominins must have had brains that conformed to the same scaling rules, irrespective of their body size. We then used those scaling rules and published estimated brain volumes for various hominin species to predict the numbers of neurons that composed their brains. We predict that Homo heidelbergensis and Homo neanderthalensis had brains with approximately 80 billion neurons, within the range of variation found in modern Homo sapiens. We propose that while the cellular scaling rules that apply to the primate brain have remained stable in hominin evolution (since they apply to simians, great apes and modern humans alike), the Colobinae and Pongidae lineages favored marked increases in body size rather than brain size from the common ancestor with the Homo lineage, while the Homo lineage seems to have favored a large brain instead of a large body, possibly due to the metabolic limitations to having both. Copyright © 2011 S. Karger AG, Basel.

Remote effects of intermittent theta burst stimulation of the human pharyngeal motor system.

PubMed

Mistry, Satish; Michou, Emilia; Rothwell, John; Hamdy, Shaheen

2012-08-01

Intermittent theta burst stimulation (iTBS) is a novel, non-invasive form of brain stimulation capable of facilitating excitability of the human primary motor cortex with therapeutic potential in the treatment of neurological conditions, such as multiple sclerosis. The objectives of this study were to evaluate the effects of iTBS on cortical properties in the human pharyngeal motor system. Transcranial magnetic stimulation (TMS)-evoked pharyngeal motor responses were recorded via a swallowed intra-luminal catheter and used to assess motor cortical pathways to the pharynx in both hemispheres before and for up to 90 min after iTBS in 15 healthy adults (nine male/six female, 22-59 years old). Active/sham iTBS comprised 600 intermittent repetitive TMS pulses, delivered in a double-blind pseudo-randomised order over each hemisphere on separate days at least 1 week apart. Abductor pollicis brevis (APB) recordings were used as control. Hemispheric interventional data were compared with sham using repeated-measures anova. iTBS was delivered at an average intensity of 43±1% of stimulator output. Compared with sham, iTBS to the hemisphere with stronger pharyngeal projections induced increased responses only in the contralateral weaker projection 60-90 min post-iTBS (maximum 54±19%, P≤0.007), with no change in stronger hemisphere responses. By contrast, iTBS to weaker projections had no significant effects (P=0.39) on either hemisphere. APB responses similarly did not change significantly (P=0.78) across all study arms. We conclude that iTBS can induce remote changes in corticobulbar excitability. While further studies will clarify the extent of these changes, iTBS holds promise as a potential treatment for dysphagia after unilateral brain damage. © 2012 The Authors. European Journal of Neuroscience © 2012 Federation of European Neuroscience Societies and Blackwell Publishing Ltd.

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

PubMed Central

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

2003-01-01

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

A New Conditionally Immortalized Human Fetal Brain Pericyte Cell Line: Establishment and Functional Characterization as a Promising Tool for Human Brain Pericyte Studies.

PubMed

Umehara, Kenta; Sun, Yuchen; Hiura, Satoshi; Hamada, Koki; Itoh, Motoyuki; Kitamura, Keita; Oshima, Motohiko; Iwama, Atsushi; Saito, Kosuke; Anzai, Naohiko; Chiba, Kan; Akita, Hidetaka; Furihata, Tomomi

2018-07-01

While pericytes wrap around microvascular endothelial cells throughout the human body, their highest coverage rate is found in the brain. Brain pericytes actively contribute to various brain functions, including the development and stabilization of the blood-brain barrier (BBB), tissue regeneration, and brain inflammation. Accordingly, detailed characterization of the functional nature of brain pericytes is important for understanding the mechanistic basis of brain physiology and pathophysiology. Herein, we report on the development of a new human brain pericyte cell line, hereafter referred to as the human brain pericyte/conditionally immortalized clone 37 (HBPC/ci37). Developed via the cell conditionally immortalization method, these cells exhibited excellent proliferative ability at 33 °C. However, when cultured at 37 °C, HBPC/ci37 cells showed a differentiated phenotype that was marked by morphological alterations and increases in several pericyte-enriched marker mRNA levels, such as platelet-derived growth factor receptor β. It was also found that HBPC/ci37 cells possessed the facilitative ability of in vitro BBB formation and differentiation into a neuronal lineage. Furthermore, HBPC/ci37 cells exhibited the typical "reactive" features of brain pericytes in response to pro-inflammatory cytokines. To summarize, our results clearly demonstrate that HBPC/ci37 cells possess the ability to perform several key brain pericyte functions while also showing the capacity for extensive and continuous proliferation. Based on these findings, it can be expected that, as a unique human brain pericyte model, HBPC/ci37 cells have the potential to contribute to significant advances in the understanding of human brain pericyte physiology and pathophysiology.

Perivascular Mesenchymal Stem Cells From the Adult Human Brain Harbor No Instrinsic Neuroectodermal but High Mesodermal Differentiation Potential.

PubMed

Lojewski, Xenia; Srimasorn, Sumitra; Rauh, Juliane; Francke, Silvan; Wobus, Manja; Taylor, Verdon; Araúzo-Bravo, Marcos J; Hallmeyer-Elgner, Susanne; Kirsch, Matthias; Schwarz, Sigrid; Schwarz, Johannes; Storch, Alexander; Hermann, Andreas

2015-10-01

Brain perivascular cells have recently been identified as a novel mesodermal cell type in the human brain. These cells reside in the perivascular niche and were shown to have mesodermal and, to a lesser extent, tissue-specific differentiation potential. Mesenchymal stem cells (MSCs) are widely proposed for use in cell therapy in many neurological disorders; therefore, it is of importance to better understand the "intrinsic" MSC population of the human brain. We systematically characterized adult human brain-derived pericytes during in vitro expansion and differentiation and compared these cells with fetal and adult human brain-derived neural stem cells (NSCs) and adult human bone marrow-derived MSCs. We found that adult human brain pericytes, which can be isolated from the hippocampus and from subcortical white matter, are-in contrast to adult human NSCs-easily expandable in monolayer cultures and show many similarities to human bone marrow-derived MSCs both regarding both surface marker expression and after whole transcriptome profile. Human brain pericytes showed a negligible propensity for neuroectodermal differentiation under various differentiation conditions but efficiently generated mesodermal progeny. Consequently, human brain pericytes resemble bone marrow-derived MSCs and might be very interesting for possible autologous and endogenous stem cell-based treatment strategies and cell therapeutic approaches for treating neurological diseases. Perivascular mesenchymal stem cells (MSCs) recently gained significant interest because of their appearance in many tissues including the human brain. MSCs were often reported as being beneficial after transplantation in the central nervous system in different neurological diseases; therefore, adult brain perivascular cells derived from human neural tissue were systematically characterized concerning neural stem cell and MSC marker expression, transcriptomics, and mesodermal and inherent neuroectodermal differentiation potential in vitro and in vivo after in utero transplantation. This study showed the lack of an innate neuronal but high mesodermal differentiation potential. Because of their relationship to mesenchymal stem cells, these adult brain perivascular mesodermal cells are of great interest for possible autologous therapeutic use. ©AlphaMed Press.

A fresh look at the male-specific region of the human Y chromosome.

PubMed

Jangravi, Zohreh; Alikhani, Mehdi; Arefnezhad, Babak; Sharifi Tabar, Mehdi; Taleahmad, Sara; Karamzadeh, Razieh; Jadaliha, Mahdieh; Mousavi, Seyed Ahmad; Ahmadi Rastegar, Diba; Parsamatin, Pouria; Vakilian, Haghighat; Mirshahvaladi, Shahab; Sabbaghian, Marjan; Mohseni Meybodi, Anahita; Mirzaei, Mehdi; Shahhoseini, Maryam; Ebrahimi, Marzieh; Piryaei, Abbas; Moosavi-Movahedi, Ali Akbar; Haynes, Paul A; Goodchild, Ann K; Nasr-Esfahani, Mohammad Hossein; Jabbari, Esmaiel; Baharvand, Hossein; Sedighi Gilani, Mohammad Ali; Gourabi, Hamid; Salekdeh, Ghasem Hosseini

2013-01-04

The Chromosome-centric Human Proteome Project (C-HPP) aims to systematically map the entire human proteome with the intent to enhance our understanding of human biology at the cellular level. This project attempts simultaneously to establish a sound basis for the development of diagnostic, prognostic, therapeutic, and preventive medical applications. In Iran, current efforts focus on mapping the proteome of the human Y chromosome. The male-specific region of the Y chromosome (MSY) is unique in many aspects and comprises 95% of the chromosome's length. The MSY continually retains its haploid state and is full of repeated sequences. It is responsible for important biological roles such as sex determination and male fertility. Here, we present the most recent update of MSY protein-encoding genes and their association with various traits and diseases including sex determination and reversal, spermatogenesis and male infertility, cancers such as prostate cancers, sex-specific effects on the brain and behavior, and graft-versus-host disease. We also present information available from RNA sequencing, protein-protein interaction, post-translational modification of MSY protein-coding genes and their implications in biological systems. An overview of Human Y chromosome Proteome Project is presented and a systematic approach is suggested to ensure that at least one of each predicted protein-coding gene's major representative proteins will be characterized in the context of its major anatomical sites of expression, its abundance, and its functional relevance in a biological and/or medical context. There are many technical and biological issues that will need to be overcome in order to accomplish the full scale mapping.

Opposing brain differences in 16p11.2 deletion and duplication carriers.

PubMed

Qureshi, Abid Y; Mueller, Sophia; Snyder, Abraham Z; Mukherjee, Pratik; Berman, Jeffrey I; Roberts, Timothy P L; Nagarajan, Srikantan S; Spiro, John E; Chung, Wendy K; Sherr, Elliott H; Buckner, Randy L

2014-08-20

Deletions and duplications of the recurrent ~600 kb chromosomal BP4-BP5 region of 16p11.2 are associated with a broad variety of neurodevelopmental outcomes including autism spectrum disorder. A clue to the pathogenesis of the copy number variant (CNV)'s effect on the brain is that the deletion is associated with a head size increase, whereas the duplication is associated with a decrease. Here we analyzed brain structure in a clinically ascertained group of human deletion (N = 25) and duplication (N = 17) carriers from the Simons Variation in Individuals Project compared with age-matched controls (N = 29 and 33, respectively). Multiple brain measures showed increased size in deletion carriers and reduced size in duplication carriers. The effects spanned global measures of intracranial volume, brain size, compartmental measures of gray matter and white matter, subcortical structures, and the cerebellum. Quantitatively, the largest effect was on the thalamus, but the collective results suggest a pervasive rather than a selective effect on the brain. Detailed analysis of cortical gray matter revealed that cortical surface area displays a strong dose-dependent effect of CNV (deletion > control > duplication), whereas average cortical thickness is less affected. These results suggest that the CNV may exert its opposing influences through mechanisms that influence early stages of embryonic brain development. Copyright © 2014 the authors 0270-6474/14/3411199-13$15.00/0.

Metabolic costs and evolutionary implications of human brain development.

PubMed

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

2014-09-09

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

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

PubMed

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

2015-01-01

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

Cognitive measure on different profiles.

PubMed

Spindola, Marilda; Carra, Giovani; Balbinot, Alexandre; Zaro, Milton A

2010-01-01

Based on neurology and cognitive science many studies are developed to understand the human model mental, getting to know how human cognition works, especially about learning processes that involve complex contents and spatial-logical reasoning. Event Related Potential - ERP - is a basic and non-invasive method of electrophysiological investigation. It can be used to assess aspects of human cognitive processing by changing the rhythm of the frequency bands brain indicate that some type of processing or neuronal behavior. This paper focuses on ERP technique to help understand cognitive pathway in subjects from different areas of knowledge when they are exposed to an external visual stimulus. In the experiment we used 2D and 3D visual stimulus in the same picture. The signals were captured using 10 (ten) Electroencephalogram - EEG - channel system developed for this project and interfaced in a ADC (Analogical Digital System) board with LabVIEW system - National Instruments. That research was performed using project of experiments technique - DOE. The signal processing were done (math and statistical techniques) showing the relationship between cognitive pathway by groups and intergroups.

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

PubMed

Cunnane, Stephen C; Crawford, Michael A

2014-12-01

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

Organoid technology for brain and therapeutics research.

PubMed

Wang, Zhi; Wang, Shu-Na; Xu, Tian-Ying; Miao, Zhu-Wei; Su, Ding-Feng; Miao, Chao-Yu

2017-10-01

Brain is one of the most complex organs in human. The current brain research is mainly based on the animal models and traditional cell culture. However, the inherent species differences between humans and animals as well as the gap between organ level and cell level make it difficult to study human brain development and associated disorders through traditional technologies. Recently, the brain organoids derived from pluripotent stem cells have been reported to recapitulate many key features of human brain in vivo, for example recapitulating the zone of putative outer radial glia cells. Brain organoids offer a new platform for scientists to study brain development, neurological diseases, drug discovery and personalized medicine, regenerative medicine, and so on. Here, we discuss the progress, applications, advantages, limitations, and prospects of brain organoid technology in neurosciences and related therapeutics. © 2017 John Wiley & Sons Ltd.

Inference of ecological and social drivers of human brain-size evolution.

PubMed

González-Forero, Mauricio; Gardner, Andy

2018-05-01

The human brain is unusually large. It has tripled in size from Australopithecines to modern humans 1 and has become almost six times larger than expected for a placental mammal of human size 2 . Brains incur high metabolic costs 3 and accordingly a long-standing question is why the large human brain has evolved 4 . The leading hypotheses propose benefits of improved cognition for overcoming ecological 5-7 , social 8-10 or cultural 11-14 challenges. However, these hypotheses are typically assessed using correlative analyses, and establishing causes for brain-size evolution remains difficult 15,16 . Here we introduce a metabolic approach that enables causal assessment of social hypotheses for brain-size evolution. Our approach yields quantitative predictions for brain and body size from formalized social hypotheses given empirical estimates of the metabolic costs of the brain. Our model predicts the evolution of adult Homo sapiens-sized brains and bodies when individuals face a combination of 60% ecological, 30% cooperative and 10% between-group competitive challenges, and suggests that between-individual competition has been unimportant for driving human brain-size evolution. Moreover, our model indicates that brain expansion in Homo was driven by ecological rather than social challenges, and was perhaps strongly promoted by culture. Our metabolic approach thus enables causal assessments that refine, refute and unify hypotheses of brain-size evolution.

Decoding Saccadic Directions Using Epidural ECoG in Non-Human Primates

PubMed Central

2017-01-01

A brain-computer interface (BCI) can be used to restore some communication as an alternative interface for patients suffering from locked-in syndrome. However, most BCI systems are based on SSVEP, P300, or motor imagery, and a diversity of BCI protocols would be needed for various types of patients. In this paper, we trained the choice saccade (CS) task in 2 non-human primate monkeys and recorded the brain signal using an epidural electrocorticogram (eECoG) to predict eye movement direction. We successfully predicted the direction of the upcoming eye movement using a support vector machine (SVM) with the brain signals after the directional cue onset and before the saccade execution. The mean accuracies were 80% for 2 directions and 43% for 4 directions. We also quantified the spatial-spectro-temporal contribution ratio using SVM recursive feature elimination (RFE). The channels over the frontal eye field (FEF), supplementary eye field (SEF), and superior parietal lobule (SPL) area were dominantly used for classification. The α-band in the spectral domain and the time bins just after the directional cue onset and just before the saccadic execution were mainly useful for prediction. A saccade based BCI paradigm can be projected in the 2D space, and will hopefully provide an intuitive and convenient communication platform for users. PMID:28665058

Time distortions in Alzheimer’s disease: a systematic review and theoretical integration

PubMed Central

El Haj, Mohamad; Kapogiannis, Dimitrios

2016-01-01

Time perception is an essential function of the human brain, which is compromised in Alzheimer’s disease (AD). Here, we review empirical findings on time distortions in AD and provide a theoretical framework that integrates time and memory distortions in AD and explains their bidirectional modulation. The review was based on a literature survey performed on the PubMed and PsycInfo databases. According to our theoretical framework, time distortions may induce decline in the ability to mentally project oneself in time (i.e., mental time travel), and consequently may contribute to an episodic memory compromise in AD. Conversely, episodic memory compromise in AD may result in a loss of the ability to retrieve information about time and/or the ability to project oneself in subjective time. The relationship between time distortions and memory decline in AD can be jointly attributed to hippocampus involvement, as this brain area supports both time perception and memory and is preferentially targeted by the neuropathological processes of AD. Clinical implications of time distortions are discussed and directions for future research are suggested. PMID:28721270

Human sexual behavior related to pathology and activity of the brain.

PubMed

Komisaruk, Barry R; Rodriguez Del Cerro, Maria Cruz

2015-01-01

Reviewed in this chapter are: (1) correlations among human sexual behavior, brain pathology, and brain activity, including caveats regarding the interpretation of "cause and effect" among these factors, and the degree to which "hypersexuality" and reported changes in sexual orientation correlated with brain pathology are uniquely sexual or are attributable to a generalized disinhibition of brain function; (2) the effects, in some cases inhibitory, in others facilitatory, on sexual behavior and motivation, of stroke, epileptic seizures, traumatic brain injury, and brain surgery; and (3) insights into sexual motivation and behavior recently gained from functional brain imaging research and its interpretive limitations. We conclude from the reviewed research that the neural orchestra underlying the symphony of human sexuality comprises, rather than brain "centers," multiple integrated brain systems, and that there are more questions than answers in our understanding of the control of human sexual behavior by the brain - a level of understanding that is still in embryonic form. © 2015 Elsevier B.V. All rights reserved.

The Human Brainnetome Atlas: A New Brain Atlas Based on Connectional Architecture.

PubMed

Fan, Lingzhong; Li, Hai; Zhuo, Junjie; Zhang, Yu; Wang, Jiaojian; Chen, Liangfu; Yang, Zhengyi; Chu, Congying; Xie, Sangma; Laird, Angela R; Fox, Peter T; Eickhoff, Simon B; Yu, Chunshui; Jiang, Tianzi

2016-08-01

The human brain atlases that allow correlating brain anatomy with psychological and cognitive functions are in transition from ex vivo histology-based printed atlases to digital brain maps providing multimodal in vivo information. Many current human brain atlases cover only specific structures, lack fine-grained parcellations, and fail to provide functionally important connectivity information. Using noninvasive multimodal neuroimaging techniques, we designed a connectivity-based parcellation framework that identifies the subdivisions of the entire human brain, revealing the in vivo connectivity architecture. The resulting human Brainnetome Atlas, with 210 cortical and 36 subcortical subregions, provides a fine-grained, cross-validated atlas and contains information on both anatomical and functional connections. Additionally, we further mapped the delineated structures to mental processes by reference to the BrainMap database. It thus provides an objective and stable starting point from which to explore the complex relationships between structure, connectivity, and function, and eventually improves understanding of how the human brain works. The human Brainnetome Atlas will be made freely available for download at http://atlas.brainnetome.org, so that whole brain parcellations, connections, and functional data will be readily available for researchers to use in their investigations into healthy and pathological states. © The Author 2016. Published by Oxford University Press.

Brain Evolution and Human Neuropsychology: The Inferential Brain Hypothesis

PubMed Central

Koscik, Timothy R.; Tranel, Daniel

2013-01-01

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

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

PubMed

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

2017-09-01

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

How Many Brains Does It Take to Build a New Light: Knowledge Management Challenges of a Transdisciplinary Project

ERIC Educational Resources Information Center

della Chiesa, Bruno; Christoph, Vanessa; Hinton, Christina

2009-01-01

The Organization for Economic Cooperation and Development's (OECD) Center for Educational Research and Innovation (CERI) carried out the "Learning Sciences and Brain Research" project (1999-2007) to investigate how neuroscience research can inform education policy and practice. This transdisciplinary project brought many challenges. Within the…

Mechanical characterization of human brain tumors from patients and comparison to potential surgical phantoms.

PubMed

Stewart, Daniel C; Rubiano, Andrés; Dyson, Kyle; Simmons, Chelsey S

2017-01-01

While mechanical properties of the brain have been investigated thoroughly, the mechanical properties of human brain tumors rarely have been directly quantified due to the complexities of acquiring human tissue. Quantifying the mechanical properties of brain tumors is a necessary prerequisite, though, to identify appropriate materials for surgical tool testing and to define target parameters for cell biology and tissue engineering applications. Since characterization methods vary widely for soft biological and synthetic materials, here, we have developed a characterization method compatible with abnormally shaped human brain tumors, mouse tumors, animal tissue and common hydrogels, which enables direct comparison among samples. Samples were tested using a custom-built millimeter-scale indenter, and resulting force-displacement data is analyzed to quantify the steady-state modulus of each sample. We have directly quantified the quasi-static mechanical properties of human brain tumors with effective moduli ranging from 0.17-16.06 kPa for various pathologies. Of the readily available and inexpensive animal tissues tested, chicken liver (steady-state modulus 0.44 ± 0.13 kPa) has similar mechanical properties to normal human brain tissue while chicken crassus gizzard muscle (steady-state modulus 3.00 ± 0.65 kPa) has similar mechanical properties to human brain tumors. Other materials frequently used to mimic brain tissue in mechanical tests, like ballistic gel and chicken breast, were found to be significantly stiffer than both normal and diseased brain tissue. We have directly compared quasi-static properties of brain tissue, brain tumors, and common mechanical surrogates, though additional tests would be required to determine more complex constitutive models.

Gestures, vocalizations, and memory in language origins.

PubMed

Aboitiz, Francisco

2012-01-01

THIS ARTICLE DISCUSSES THE POSSIBLE HOMOLOGIES BETWEEN THE HUMAN LANGUAGE NETWORKS AND COMPARABLE AUDITORY PROJECTION SYSTEMS IN THE MACAQUE BRAIN, IN AN ATTEMPT TO RECONCILE TWO EXISTING VIEWS ON LANGUAGE EVOLUTION: one that emphasizes hand control and gestures, and the other that emphasizes auditory-vocal mechanisms. The capacity for language is based on relatively well defined neural substrates whose rudiments have been traced in the non-human primate brain. At its core, this circuit constitutes an auditory-vocal sensorimotor circuit with two main components, a "ventral pathway" connecting anterior auditory regions with anterior ventrolateral prefrontal areas, and a "dorsal pathway" connecting auditory areas with parietal areas and with posterior ventrolateral prefrontal areas via the arcuate fasciculus and the superior longitudinal fasciculus. In humans, the dorsal circuit is especially important for phonological processing and phonological working memory, capacities that are critical for language acquisition and for complex syntax processing. In the macaque, the homolog of the dorsal circuit overlaps with an inferior parietal-premotor network for hand and gesture selection that is under voluntary control, while vocalizations are largely fixed and involuntary. The recruitment of the dorsal component for vocalization behavior in the human lineage, together with a direct cortical control of the subcortical vocalizing system, are proposed to represent a fundamental innovation in human evolution, generating an inflection point that permitted the explosion of vocal language and human communication. In this context, vocal communication and gesturing have a common history in primate communication.

Toxoplasma Modulates Signature Pathways of Human Epilepsy, Neurodegeneration & Cancer.

PubMed

Ngô, Huân M; Zhou, Ying; Lorenzi, Hernan; Wang, Kai; Kim, Taek-Kyun; Zhou, Yong; El Bissati, Kamal; Mui, Ernest; Fraczek, Laura; Rajagopala, Seesandra V; Roberts, Craig W; Henriquez, Fiona L; Montpetit, Alexandre; Blackwell, Jenefer M; Jamieson, Sarra E; Wheeler, Kelsey; Begeman, Ian J; Naranjo-Galvis, Carlos; Alliey-Rodriguez, Ney; Davis, Roderick G; Soroceanu, Liliana; Cobbs, Charles; Steindler, Dennis A; Boyer, Kenneth; Noble, A Gwendolyn; Swisher, Charles N; Heydemann, Peter T; Rabiah, Peter; Withers, Shawn; Soteropoulos, Patricia; Hood, Leroy; McLeod, Rima

2017-09-13

One third of humans are infected lifelong with the brain-dwelling, protozoan parasite, Toxoplasma gondii. Approximately fifteen million of these have congenital toxoplasmosis. Although neurobehavioral disease is associated with seropositivity, causality is unproven. To better understand what this parasite does to human brains, we performed a comprehensive systems analysis of the infected brain: We identified susceptibility genes for congenital toxoplasmosis in our cohort of infected humans and found these genes are expressed in human brain. Transcriptomic and quantitative proteomic analyses of infected human, primary, neuronal stem and monocytic cells revealed effects on neurodevelopment and plasticity in neural, immune, and endocrine networks. These findings were supported by identification of protein and miRNA biomarkers in sera of ill children reflecting brain damage and T. gondii infection. These data were deconvoluted using three systems biology approaches: "Orbital-deconvolution" elucidated upstream, regulatory pathways interconnecting human susceptibility genes, biomarkers, proteomes, and transcriptomes. "Cluster-deconvolution" revealed visual protein-protein interaction clusters involved in processes affecting brain functions and circuitry, including lipid metabolism, leukocyte migration and olfaction. Finally, "disease-deconvolution" identified associations between the parasite-brain interactions and epilepsy, movement disorders, Alzheimer's disease, and cancer. This "reconstruction-deconvolution" logic provides templates of progenitor cells' potentiating effects, and components affecting human brain parasitism and diseases.

Educating the Human Brain. Human Brain Development Series

ERIC Educational Resources Information Center

Posner, Michael I.; Rothbart, Mary K.

2006-01-01

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

From Toxins Targeting Ligand Gated Ion Channels to Therapeutic Molecules

PubMed Central

Nasiripourdori, Adak; Taly, Valérie; Grutter, Thomas; Taly, Antoine

2011-01-01

Ligand-gated ion channels (LGIC) play a central role in inter-cellular communication. This key function has two consequences: (i) these receptor channels are major targets for drug discovery because of their potential involvement in numerous human brain diseases; (ii) they are often found to be the target of plant and animal toxins. Together this makes toxin/receptor interactions important to drug discovery projects. Therefore, toxins acting on LGIC are presented and their current/potential therapeutic uses highlighted. PMID:22069709

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

PubMed

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

2011-06-17

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

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

PubMed Central

2016-01-01

An all-chain-wireless brain-to-brain system (BTBS), which enabled motion control of a cyborg cockroach via human brain, was developed in this work. Steady-state visual evoked potential (SSVEP) based brain-computer interface (BCI) was used in this system for recognizing human motion intention and an optimization algorithm was proposed in SSVEP to improve online performance of the BCI. The cyborg cockroach was developed by surgically integrating a portable microstimulator that could generate invasive electrical nerve stimulation. Through Bluetooth communication, specific electrical pulse trains could be triggered from the microstimulator by BCI commands and were sent through the antenna nerve to stimulate the brain of cockroach. Serial experiments were designed and conducted to test overall performance of the BTBS with six human subjects and three cockroaches. The experimental results showed that the online classification accuracy of three-mode BCI increased from 72.86% to 78.56% by 5.70% using the optimization algorithm and the mean response accuracy of the cyborgs using this system reached 89.5%. Moreover, the results also showed that the cyborg could be navigated by the human brain to complete walking along an S-shape track with the success rate of about 20%, suggesting the proposed BTBS established a feasible functional information transfer pathway from the human brain to the cockroach brain. PMID:26982717

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

PubMed

Li, Guangye; Zhang, Dingguo

2016-01-01

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

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

PubMed

Aldridge, Kristina

2011-01-01

Although human evolution is characterized by a vast increase in brain size, it is not clear whether or not certain regions of the brain are enlarged disproportionately in humans, or how this enlargement relates to differences in overall neural morphology. The aim of this study is to determine whether or not there are specific suites of features that distinguish the morphology of the human brain from that of apes. The study sample consists of whole brain, in vivo magnetic resonance images (MRIs) of anatomically modern humans (Homo sapiens sapiens) and five ape species (gibbons, orangutans, gorillas, chimpanzees, bonobos). Twenty-nine 3D landmarks, including surface and internal features of the brain were located on 3D MRI reconstructions of each individual using MEASURE software. Landmark coordinate data were scaled for differences in size and analyzed using Euclidean Distance Matrix Analysis (EDMA) to statistically compare the brains of each non-human ape species to the human sample. Results of analyses show both a pattern of brain morphology that is consistently different between all apes and humans, as well as patterns that differ among species. Further, both the consistent and species-specific patterns include cortical and subcortical features. The pattern that remains consistent across species indicates a morphological reorganization of 1) relationships between cortical and subcortical frontal structures, 2) expansion of the temporal lobe and location of the amygdala, and 3) expansion of the anterior parietal region. Additionally, results demonstrate that, although there is a pattern of morphology that uniquely defines the human brain, there are also patterns that uniquely differentiate human morphology from the morphology of each non-human ape species, indicating that reorganization of neural morphology occurred at the evolutionary divergence of each of these groups. Copyright © 2010 Elsevier Ltd. All rights reserved.

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

PubMed Central

Aldridge, Kristina

2010-01-01

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

Endurance Exercise as an “Endogenous” Neuro-enhancement Strategy to Facilitate Motor Learning

PubMed Central

Taubert, Marco; Villringer, Arno; Lehmann, Nico

2015-01-01

Endurance exercise improves cardiovascular and musculoskeletal function and may also increase the information processing capacities of the brain. Animal and human research from the past decade demonstrated widespread exercise effects on brain structure and function at the systems-, cellular-, and molecular level of brain organization. These neurobiological mechanisms may explain the well-established positive influence of exercise on performance in various behavioral domains but also its contribution to improved skill learning and neuroplasticity. With respect to the latter, only few empirical and theoretical studies are available to date. The aim of this review is (i) to summarize the existing neurobiological and behavioral evidence arguing for endurance exercise-induced improvements in motor learning and (ii) to develop hypotheses about the mechanistic link between exercise and improved learning. We identify major knowledge gaps that need to be addressed by future research projects to advance our understanding of how exercise should be organized to optimize motor learning. PMID:26834602

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

Integrative Biological Analysis For Neuropsychopharmacology

PubMed Central

Emmett, Mark R; Kroes, Roger A; Moskal, Joseph R; Conrad, Charles A; Priebe, Waldemar; Laezza, Fernanda; Meyer-Baese, Anke; Nilsson, Carol L

2014-01-01

Although advances in psychotherapy have been made in recent years, drug discovery for brain diseases such as schizophrenia and mood disorders has stagnated. The need for new biomarkers and validated therapeutic targets in the field of neuropsychopharmacology is widely unmet. The brain is the most complex part of human anatomy from the standpoint of number and types of cells, their interconnections, and circuitry. To better meet patient needs, improved methods to approach brain studies by understanding functional networks that interact with the genome are being developed. The integrated biological approaches—proteomics, transcriptomics, metabolomics, and glycomics—have a strong record in several areas of biomedicine, including neurochemistry and neuro-oncology. Published applications of an integrated approach to projects of neurological, psychiatric, and pharmacological natures are still few but show promise to provide deep biological knowledge derived from cells, animal models, and clinical materials. Future studes that yield insights based on integrated analyses promise to deliver new therapeutic targets and biomarkers for personalized medicine. PMID:23800968

Brain Activity and Human Unilateral Chewing

PubMed Central

Quintero, A.; Ichesco, E.; Myers, C.; Schutt, R.; Gerstner, G.E.

2012-01-01

Brain mechanisms underlying mastication have been studied in non-human mammals but less so in humans. We used functional magnetic resonance imaging (fMRI) to evaluate brain activity in humans during gum chewing. Chewing was associated with activations in the cerebellum, motor cortex and caudate, cingulate, and brainstem. We also divided the 25-second chew-blocks into 5 segments of equal 5-second durations and evaluated activations within and between each of the 5 segments. This analysis revealed activation clusters unique to the initial segment, which may indicate brain regions involved with initiating chewing. Several clusters were uniquely activated during the last segment as well, which may represent brain regions involved with anticipatory or motor events associated with the end of the chew-block. In conclusion, this study provided evidence for specific brain areas associated with chewing in humans and demonstrated that brain activation patterns may dynamically change over the course of chewing sequences. PMID:23103631

Human Brain Modeling with Its Anatomical Structure and Realistic Material Properties for Brain Injury Prediction.

PubMed

Atsumi, Noritoshi; Nakahira, Yuko; Tanaka, Eiichi; Iwamoto, Masami

2018-05-01

Impairments of executive brain function after traumatic brain injury (TBI) due to head impacts in traffic accidents need to be obviated. Finite element (FE) analyses with a human brain model facilitate understanding of the TBI mechanisms. However, conventional brain FE models do not suitably describe the anatomical structure in the deep brain, which is a critical region for executive brain function, and the material properties of brain parenchyma. In this study, for better TBI prediction, a novel brain FE model with anatomical structure in the deep brain was developed. The developed model comprises a constitutive model of brain parenchyma considering anisotropy and strain rate dependency. Validation was performed against postmortem human subject test data associated with brain deformation during head impact. Brain injury analyses were performed using head acceleration curves obtained from reconstruction analysis of rear-end collision with a human whole-body FE model. The difference in structure was found to affect the regions of strain concentration, while the difference in material model contributed to the peak strain value. The injury prediction result by the proposed model was consistent with the characteristics in the neuroimaging data of TBI patients due to traffic accidents.

A simple rapid process for semi-automated brain extraction from magnetic resonance images of the whole mouse head.

PubMed

Delora, Adam; Gonzales, Aaron; Medina, Christopher S; Mitchell, Adam; Mohed, Abdul Faheem; Jacobs, Russell E; Bearer, Elaine L

2016-01-15

Magnetic resonance imaging (MRI) is a well-developed technique in neuroscience. Limitations in applying MRI to rodent models of neuropsychiatric disorders include the large number of animals required to achieve statistical significance, and the paucity of automation tools for the critical early step in processing, brain extraction, which prepares brain images for alignment and voxel-wise statistics. This novel timesaving automation of template-based brain extraction ("skull-stripping") is capable of quickly and reliably extracting the brain from large numbers of whole head images in a single step. The method is simple to install and requires minimal user interaction. This method is equally applicable to different types of MR images. Results were evaluated with Dice and Jacquard similarity indices and compared in 3D surface projections with other stripping approaches. Statistical comparisons demonstrate that individual variation of brain volumes are preserved. A downloadable software package not otherwise available for extraction of brains from whole head images is included here. This software tool increases speed, can be used with an atlas or a template from within the dataset, and produces masks that need little further refinement. Our new automation can be applied to any MR dataset, since the starting point is a template mask generated specifically for that dataset. The method reliably and rapidly extracts brain images from whole head images, rendering them useable for subsequent analytical processing. This software tool will accelerate the exploitation of mouse models for the investigation of human brain disorders by MRI. Copyright © 2015 Elsevier B.V. All rights reserved.

Distinct prediction errors in mesostriatal circuits of the human brain mediate learning about the values of both states and actions: evidence from high-resolution fMRI.

PubMed

Colas, Jaron T; Pauli, Wolfgang M; Larsen, Tobias; Tyszka, J Michael; O'Doherty, John P

2017-10-01

Prediction-error signals consistent with formal models of "reinforcement learning" (RL) have repeatedly been found within dopaminergic nuclei of the midbrain and dopaminoceptive areas of the striatum. However, the precise form of the RL algorithms implemented in the human brain is not yet well determined. Here, we created a novel paradigm optimized to dissociate the subtypes of reward-prediction errors that function as the key computational signatures of two distinct classes of RL models-namely, "actor/critic" models and action-value-learning models (e.g., the Q-learning model). The state-value-prediction error (SVPE), which is independent of actions, is a hallmark of the actor/critic architecture, whereas the action-value-prediction error (AVPE) is the distinguishing feature of action-value-learning algorithms. To test for the presence of these prediction-error signals in the brain, we scanned human participants with a high-resolution functional magnetic-resonance imaging (fMRI) protocol optimized to enable measurement of neural activity in the dopaminergic midbrain as well as the striatal areas to which it projects. In keeping with the actor/critic model, the SVPE signal was detected in the substantia nigra. The SVPE was also clearly present in both the ventral striatum and the dorsal striatum. However, alongside these purely state-value-based computations we also found evidence for AVPE signals throughout the striatum. These high-resolution fMRI findings suggest that model-free aspects of reward learning in humans can be explained algorithmically with RL in terms of an actor/critic mechanism operating in parallel with a system for more direct action-value learning.

Distinct prediction errors in mesostriatal circuits of the human brain mediate learning about the values of both states and actions: evidence from high-resolution fMRI

PubMed Central

Pauli, Wolfgang M.; Larsen, Tobias; Tyszka, J. Michael; O’Doherty, John P.

2017-01-01

Prediction-error signals consistent with formal models of “reinforcement learning” (RL) have repeatedly been found within dopaminergic nuclei of the midbrain and dopaminoceptive areas of the striatum. However, the precise form of the RL algorithms implemented in the human brain is not yet well determined. Here, we created a novel paradigm optimized to dissociate the subtypes of reward-prediction errors that function as the key computational signatures of two distinct classes of RL models—namely, “actor/critic” models and action-value-learning models (e.g., the Q-learning model). The state-value-prediction error (SVPE), which is independent of actions, is a hallmark of the actor/critic architecture, whereas the action-value-prediction error (AVPE) is the distinguishing feature of action-value-learning algorithms. To test for the presence of these prediction-error signals in the brain, we scanned human participants with a high-resolution functional magnetic-resonance imaging (fMRI) protocol optimized to enable measurement of neural activity in the dopaminergic midbrain as well as the striatal areas to which it projects. In keeping with the actor/critic model, the SVPE signal was detected in the substantia nigra. The SVPE was also clearly present in both the ventral striatum and the dorsal striatum. However, alongside these purely state-value-based computations we also found evidence for AVPE signals throughout the striatum. These high-resolution fMRI findings suggest that model-free aspects of reward learning in humans can be explained algorithmically with RL in terms of an actor/critic mechanism operating in parallel with a system for more direct action-value learning. PMID:29049406

A dedicated neonatal brain imaging system

PubMed Central

Winchman, Tobias; Padormo, Francesco; Teixeira, Rui; Wurie, Julia; Sharma, Maryanne; Fox, Matthew; Hutter, Jana; Cordero‐Grande, Lucilio; Price, Anthony N.; Allsop, Joanna; Bueno‐Conde, Jose; Tusor, Nora; Arichi, Tomoki; Edwards, A. D.; Rutherford, Mary A.; Counsell, Serena J.; Hajnal, Joseph V.

2016-01-01

Purpose The goal of the Developing Human Connectome Project is to acquire MRI in 1000 neonates to create a dynamic map of human brain connectivity during early development. High‐quality imaging in this cohort without sedation presents a number of technical and practical challenges. Methods We designed a neonatal brain imaging system (NBIS) consisting of a dedicated 32‐channel receive array coil and a positioning device that allows placement of the infant's head deep into the coil for maximum signal‐to‐noise ratio (SNR). Disturbance to the infant was minimized by using an MRI‐compatible trolley to prepare and transport the infant and by employing a slow ramp‐up and continuation of gradient noise during scanning. Scan repeats were minimized by using a restart capability for diffusion MRI and retrospective motion correction. We measured the 1) SNR gain, 2) number of infants with a completed scan protocol, and 3) number of anatomical images with no motion artifact using NBIS compared with using an adult 32‐channel head coil. Results The NBIS has 2.4 times the SNR of the adult coil and 90% protocol completion rate. Conclusion The NBIS allows advanced neonatal brain imaging techniques to be employed in neonatal brain imaging with high protocol completion rates. Magn Reson Med 78:794–804, 2017. © 2016 The Authors Magnetic Resonance in Medicine published by Wiley Periodicals, Inc. on behalf of International Society for Magnetic Resonance in Medicine. This is an open access article under the terms of the Creative Commons Attribution‐NonCommercial‐NoDerivs License, which permits use and distribution in any medium, provided the original work is properly cited, the use is non‐commercial and no modifications or adaptations are made. PMID:27643791

PANDA: a pipeline toolbox for analyzing brain diffusion images.

PubMed

Cui, Zaixu; Zhong, Suyu; Xu, Pengfei; He, Yong; Gong, Gaolang

2013-01-01

Diffusion magnetic resonance imaging (dMRI) is widely used in both scientific research and clinical practice in in-vivo studies of the human brain. While a number of post-processing packages have been developed, fully automated processing of dMRI datasets remains challenging. Here, we developed a MATLAB toolbox named "Pipeline for Analyzing braiN Diffusion imAges" (PANDA) for fully automated processing of brain diffusion images. The processing modules of a few established packages, including FMRIB Software Library (FSL), Pipeline System for Octave and Matlab (PSOM), Diffusion Toolkit and MRIcron, were employed in PANDA. Using any number of raw dMRI datasets from different subjects, in either DICOM or NIfTI format, PANDA can automatically perform a series of steps to process DICOM/NIfTI to diffusion metrics [e.g., fractional anisotropy (FA) and mean diffusivity (MD)] that are ready for statistical analysis at the voxel-level, the atlas-level and the Tract-Based Spatial Statistics (TBSS)-level and can finish the construction of anatomical brain networks for all subjects. In particular, PANDA can process different subjects in parallel, using multiple cores either in a single computer or in a distributed computing environment, thus greatly reducing the time cost when dealing with a large number of datasets. In addition, PANDA has a friendly graphical user interface (GUI), allowing the user to be interactive and to adjust the input/output settings, as well as the processing parameters. As an open-source package, PANDA is freely available at http://www.nitrc.org/projects/panda/. This novel toolbox is expected to substantially simplify the image processing of dMRI datasets and facilitate human structural connectome studies.

PANDA: a pipeline toolbox for analyzing brain diffusion images

PubMed Central

Cui, Zaixu; Zhong, Suyu; Xu, Pengfei; He, Yong; Gong, Gaolang

2013-01-01

Diffusion magnetic resonance imaging (dMRI) is widely used in both scientific research and clinical practice in in-vivo studies of the human brain. While a number of post-processing packages have been developed, fully automated processing of dMRI datasets remains challenging. Here, we developed a MATLAB toolbox named “Pipeline for Analyzing braiN Diffusion imAges” (PANDA) for fully automated processing of brain diffusion images. The processing modules of a few established packages, including FMRIB Software Library (FSL), Pipeline System for Octave and Matlab (PSOM), Diffusion Toolkit and MRIcron, were employed in PANDA. Using any number of raw dMRI datasets from different subjects, in either DICOM or NIfTI format, PANDA can automatically perform a series of steps to process DICOM/NIfTI to diffusion metrics [e.g., fractional anisotropy (FA) and mean diffusivity (MD)] that are ready for statistical analysis at the voxel-level, the atlas-level and the Tract-Based Spatial Statistics (TBSS)-level and can finish the construction of anatomical brain networks for all subjects. In particular, PANDA can process different subjects in parallel, using multiple cores either in a single computer or in a distributed computing environment, thus greatly reducing the time cost when dealing with a large number of datasets. In addition, PANDA has a friendly graphical user interface (GUI), allowing the user to be interactive and to adjust the input/output settings, as well as the processing parameters. As an open-source package, PANDA is freely available at http://www.nitrc.org/projects/panda/. This novel toolbox is expected to substantially simplify the image processing of dMRI datasets and facilitate human structural connectome studies. PMID:23439846

High-throughput dual-colour precision imaging for brain-wide connectome with cytoarchitectonic landmarks at the cellular level

PubMed Central

Gong, Hui; Xu, Dongli; Yuan, Jing; Li, Xiangning; Guo, Congdi; Peng, Jie; Li, Yuxin; Schwarz, Lindsay A.; Li, Anan; Hu, Bihe; Xiong, Benyi; Sun, Qingtao; Zhang, Yalun; Liu, Jiepeng; Zhong, Qiuyuan; Xu, Tonghui; Zeng, Shaoqun; Luo, Qingming

2016-01-01

The precise annotation and accurate identification of neural structures are prerequisites for studying mammalian brain function. The orientation of neurons and neural circuits is usually determined by mapping brain images to coarse axial-sampling planar reference atlases. However, individual differences at the cellular level likely lead to position errors and an inability to orient neural projections at single-cell resolution. Here, we present a high-throughput precision imaging method that can acquire a co-localized brain-wide data set of both fluorescent-labelled neurons and counterstained cell bodies at a voxel size of 0.32 × 0.32 × 2.0 μm in 3 days for a single mouse brain. We acquire mouse whole-brain imaging data sets of multiple types of neurons and projections with anatomical annotation at single-neuron resolution. The results show that the simultaneous acquisition of labelled neural structures and cytoarchitecture reference in the same brain greatly facilitates precise tracing of long-range projections and accurate locating of nuclei. PMID:27374071

Metabolic costs and evolutionary implications of human brain development

PubMed Central

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

2014-01-01

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

Neuron-Enriched Gene Expression Patterns are Regionally Anti-Correlated with Oligodendrocyte-Enriched Patterns in the Adult Mouse and Human Brain

PubMed Central

Tan, Powell Patrick Cheng; French, Leon; Pavlidis, Paul

2013-01-01

An important goal in neuroscience is to understand gene expression patterns in the brain. The recent availability of comprehensive and detailed expression atlases for mouse and human creates opportunities to discover global patterns and perform cross-species comparisons. Recently we reported that the major source of variation in gene transcript expression in the adult normal mouse brain can be parsimoniously explained as reflecting regional variation in glia to neuron ratios, and is correlated with degree of connectivity and location in the brain along the anterior-posterior axis. Here we extend this investigation to two gene expression assays of adult normal human brains that consisted of over 300 brain region samples, and perform comparative analyses of brain-wide expression patterns to the mouse. We performed principal components analysis (PCA) on the regional gene expression of the adult human brain to identify the expression pattern that has the largest variance. As in the mouse, we observed that the first principal component is composed of two anti-correlated patterns enriched in oligodendrocyte and neuron markers respectively. However, we also observed interesting discordant patterns between the two species. For example, a few mouse neuron markers show expression patterns that are more correlated with the human oligodendrocyte-enriched pattern and vice-versa. In conclusion, our work provides insights into human brain function and evolution by probing global relationships between regional cell type marker expression patterns in the human and mouse brain. PMID:23440889

Neuron-Enriched Gene Expression Patterns are Regionally Anti-Correlated with Oligodendrocyte-Enriched Patterns in the Adult Mouse and Human Brain.

PubMed

Tan, Powell Patrick Cheng; French, Leon; Pavlidis, Paul

2013-01-01

An important goal in neuroscience is to understand gene expression patterns in the brain. The recent availability of comprehensive and detailed expression atlases for mouse and human creates opportunities to discover global patterns and perform cross-species comparisons. Recently we reported that the major source of variation in gene transcript expression in the adult normal mouse brain can be parsimoniously explained as reflecting regional variation in glia to neuron ratios, and is correlated with degree of connectivity and location in the brain along the anterior-posterior axis. Here we extend this investigation to two gene expression assays of adult normal human brains that consisted of over 300 brain region samples, and perform comparative analyses of brain-wide expression patterns to the mouse. We performed principal components analysis (PCA) on the regional gene expression of the adult human brain to identify the expression pattern that has the largest variance. As in the mouse, we observed that the first principal component is composed of two anti-correlated patterns enriched in oligodendrocyte and neuron markers respectively. However, we also observed interesting discordant patterns between the two species. For example, a few mouse neuron markers show expression patterns that are more correlated with the human oligodendrocyte-enriched pattern and vice-versa. In conclusion, our work provides insights into human brain function and evolution by probing global relationships between regional cell type marker expression patterns in the human and mouse brain.

The Molecular Basis of Human Brain Evolution.

PubMed

Enard, Wolfgang

2016-10-24

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

Systems Neuroscience of Psychosis: Mapping Schizophrenia Symptoms onto Brain Systems.

PubMed

Strik, Werner; Stegmayer, Katharina; Walther, Sebastian; Dierks, Thomas

2017-01-01

Schizophrenia research has been in a deadlock for many decades. Despite important advances in clinical treatment, there are still major concerns regarding long-term psychosocial reintegration and disease management, biological heterogeneity, unsatisfactory predictors of individual course and treatment strategies, and a confusing variety of controversial theories about its etiology and pathophysiological mechanisms. In the present perspective on schizophrenia research, we first discuss a methodological pitfall in contemporary schizophrenia research inherent in the attempt to link mental phenomena with the brain: we claim that the time-honored phenomenological method of defining mental symptoms should not be contaminated with the naturalistic approach of modern neuroscience. We then describe our Systems Neuroscience of Psychosis (SyNoPsis) project, which aims to overcome this intrinsic problem of psychiatric research. Considering schizophrenia primarily as a disorder of interindividual communication, we developed a neurobiologically informed semiotics of psychotic disorders, as well as an operational clinical rating scale. The novel psychopathology allows disentangling the clinical manifestations of schizophrenia into behavioral domains matching the functions of three well-described higher-order corticobasal brain systems involved in interindividual human communication, namely, the limbic, associative, and motor loops, including their corticocortical sensorimotor connections. The results of several empirical studies support the hypothesis that the proposed three-dimensional symptom structure, segregated into the affective, the language, and the motor domain, can be specifically mapped onto structural and functional abnormalities of the respective brain systems. New pathophysiological hypotheses derived from this brain system-oriented approach have helped to develop and improve novel treatment strategies with noninvasive brain stimulation and practicable clinical parameters. In clinical practice, the novel psychopathology allows confining the communication deficits of the individual patient, shifting attention from the symptoms to the intact resources. We have studied this approach and observed important advantages for therapeutic alliances, personalized treatment, and de-escalation strategies. Future studies will further conjoin clinical definitions of psychotic symptoms with brain structures and functions, and disentangle structural and functional deficit patterns within these systems to identify neurobiologically distinct subsyndromes. Neurobiologically homogeneous patient groups may provide new momentum for treatment research. Finally, lessons learned from schizophrenia research may contribute to developing a comprehensive perspective on human experience and behavior that integrates methodologically distinct, but internally consistent, insights from humanities and neuroscience. © 2017 S. Karger AG, Basel.

Mechanical characterization of human brain tumors from patients and comparison to potential surgical phantoms

PubMed Central

Rubiano, Andrés; Dyson, Kyle; Simmons, Chelsey S.

2017-01-01

While mechanical properties of the brain have been investigated thoroughly, the mechanical properties of human brain tumors rarely have been directly quantified due to the complexities of acquiring human tissue. Quantifying the mechanical properties of brain tumors is a necessary prerequisite, though, to identify appropriate materials for surgical tool testing and to define target parameters for cell biology and tissue engineering applications. Since characterization methods vary widely for soft biological and synthetic materials, here, we have developed a characterization method compatible with abnormally shaped human brain tumors, mouse tumors, animal tissue and common hydrogels, which enables direct comparison among samples. Samples were tested using a custom-built millimeter-scale indenter, and resulting force-displacement data is analyzed to quantify the steady-state modulus of each sample. We have directly quantified the quasi-static mechanical properties of human brain tumors with effective moduli ranging from 0.17–16.06 kPa for various pathologies. Of the readily available and inexpensive animal tissues tested, chicken liver (steady-state modulus 0.44 ± 0.13 kPa) has similar mechanical properties to normal human brain tissue while chicken crassus gizzard muscle (steady-state modulus 3.00 ± 0.65 kPa) has similar mechanical properties to human brain tumors. Other materials frequently used to mimic brain tissue in mechanical tests, like ballistic gel and chicken breast, were found to be significantly stiffer than both normal and diseased brain tissue. We have directly compared quasi-static properties of brain tissue, brain tumors, and common mechanical surrogates, though additional tests would be required to determine more complex constitutive models. PMID:28582392

Transcriptional Landscape of the Prenatal Human Brain

PubMed Central

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

2014-01-01

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

Navigating conjugated polymer actuated neural probes in a brain phantom

NASA Astrophysics Data System (ADS)

Daneshvar, Eugene D.; Kipke, Daryl; Smela, Elisabeth

2012-04-01

Neural probe insertion methods have a direct impact on the longevity of the device in the brain. Initial tissue and vascular damage caused by the probe entering the brain triggers a chronic tissue response that is known to attenuate neural recordings and ultimately encapsulate the probes. Smaller devices have been found to evoke reduced inflammatory response. One way to record from undamaged neural networks may be to position the electrode sites away from the probe. To investigate this approach, we are developing probes with controllably movable electrode projections, which would move outside of the zone that is damaged by the insertion of the larger probe. The objective of this study was to test the capability of conjugated polymer bilayer actuators to actuate neural electrode projections from a probe shank into a transparent brain phantom. Parylene neural probe devices, having five electrode projections with actuating segments and with varying widths (50 - 250 μm) and lengths (200 - 1000 μm) were fabricated. The electroactive polymer polypyrrole (PPy) was used to bend or flatten the projections. The devices were inserted into the brain phantom using an electronic microdrive while simultaneously activating the actuators. Deflections were quantified based on video images. The electrode projections were successfully controlled to either remain flat or to actuate out-of-plane and into the brain phantom during insertion. The projection width had a significant effect on their ability to deflect within the phantom, with thinner probes deflecting but not the wider ones. Thus, small integrated conjugated polymer actuators may enable multiple neuro-experiments and applications not possible before.

Dynamics of convulsive seizure termination and postictal generalized EEG suppression

PubMed Central

Bauer, Prisca R.; Thijs, Roland D.; Lamberts, Robert J.; Velis, Demetrios N.; Visser, Gerhard H.; Tolner, Else A.; Sander, Josemir W.; Lopes da Silva, Fernando H.; Kalitzin, Stiliyan N.

2017-01-01

Abstract It is not fully understood how seizures terminate and why some seizures are followed by a period of complete brain activity suppression, postictal generalized EEG suppression. This is clinically relevant as there is a potential association between postictal generalized EEG suppression, cardiorespiratory arrest and sudden death following a seizure. We combined human encephalographic seizure data with data of a computational model of seizures to elucidate the neuronal network dynamics underlying seizure termination and the postictal generalized EEG suppression state. A multi-unit computational neural mass model of epileptic seizure termination and postictal recovery was developed. The model provided three predictions that were validated in EEG recordings of 48 convulsive seizures from 48 subjects with refractory focal epilepsy (20 females, age range 15–61 years). The duration of ictal and postictal generalized EEG suppression periods in human EEG followed a gamma probability distribution indicative of a deterministic process (shape parameter 2.6 and 1.5, respectively) as predicted by the model. In the model and in humans, the time between two clonic bursts increased exponentially from the start of the clonic phase of the seizure. The terminal interclonic interval, calculated using the projected terminal value of the log-linear fit of the clonic frequency decrease was correlated with the presence and duration of postictal suppression. The projected terminal interclonic interval explained 41% of the variation in postictal generalized EEG suppression duration (P < 0.02). Conversely, postictal generalized EEG suppression duration explained 34% of the variation in the last interclonic interval duration. Our findings suggest that postictal generalized EEG suppression is a separate brain state and that seizure termination is a plastic and autonomous process, reflected in increased duration of interclonic intervals that determine the duration of postictal generalized EEG suppression. PMID:28073789

Patterns of craniofacial integration in extant Homo, Pan, and Gorilla.

PubMed

Polanski, Joshua M; Franciscus, Robert G

2006-09-01

Brain size increased greatly during Pleistocene human evolution, while overall facial and dentognathic size decreased markedly. This mosaic pattern is due to either selective forces that acted uniquely on each functional unit in a modularized, developmentally uncoupled craniofacial complex, or alternatively, selection that acted primarily on one unit, with the other responding passively as part of a coevolved set of ontogenetically and evolutionarily integrated structures. Using conditional independence modeling on homologous linear measurements of the height, breadth, and depth of the cranium in Pan (n = 95), Gorilla (n = 102), and recent Homo (n = 120), we reject the null hypothesis of equal levels of overall cranial integration. While all three groups share the pattern of greater neurocranial integration with distinct separation between the face and neurocranium (modularization), family differences do exist. The apes are more integrated in their entire crania, but display a particularly strong pattern of integration within the facial complex related to prognathism. Modern humans display virtually no facial integration, a pattern which is likely related to their markedly decreased facial projection. Modern humans also differ from their great ape counterparts in being more integrated within the breadth dimension of the cranial vault, likely tied to the increase in brain size and eventual globularity seen in human evolution. That the modern human integration pattern differs from the ancestral African great ape pattern along the inverse neurocranial-facial trend seen in human evolution indicates that this shift in the pattern of integration is evolutionarily significant, and may help to clarify aspects of the current debate over defining modern humans. 2006 Wiley-Liss, Inc.

Descending brain neurons in larval lamprey: Spinal projection patterns and initiation of locomotion

PubMed Central

Shaw, Albert C.; Jackson, Adam W.; Holmes, Tamra; Thurman, Suzie; Davis, G.R.; McClellan, Andrew D.

2010-01-01

In larval lamprey, partial lesions were made in the rostral spinal cord to determine which spinal tracts are important for descending activation of locomotion and to identify descending brain neurons that project in these tracts. In whole animals and in vitro brain/spinal cord preparations, brain-initiated spinal locomotor activity was present when the lateral or intermediate spinal tracts were spared but usually was abolished when the medial tracts were spared. We previously showed that descending brain neurons are located in eleven cell groups, including reticulospinal (RS) neurons in the mesenecephalic reticular nucleus (MRN) as well as the anterior (ARRN), middle (MRRN), and posterior (PRRN) rhombencephalic reticular nuclei. Other descending brain neurons are located in the diencephalic (Di) as well as the anterolateral (ALV), dorsolateral (DLV), and posterolateral (PLV) vagal groups. In the present study, the Mauthner and auxillary Mauthner cells, most neurons in the Di, ALV, DLV, and PLV cell groups, and some neurons in the ARRN and PRRN had crossed descending axons. The majority of neurons projecting in medial spinal tracts included large identified Müller cells and neurons in the Di, MRN, ALV, and DLV. Axons of individual descending brain neurons usually did not switch spinal tracts, have branches in multiple tracts, or cross the midline within the rostral cord. Most neurons that projected in the lateral/intermediate spinal tracts were in the ARRN, MRRN, and PRRN. Thus, output neurons of the locomotor command system are distributed in several reticular nuclei, whose neurons project in relatively wide areas of the cord. PMID:20510243

Conversion of Clinical Data from the NABISH 1 and 2 into FITBIR

DTIC Science & Technology

2015-10-01

Research (FITBIR) Informatics System. Data sets from the National Acute Brain Injury Study: Hypothermia (NABISH) projects will be reviewed, analyzed, and...Keywords and Acronyms: Common Data Elements (CDEs) FITBIR – the Federal Interagency Traumatic Brain Injury Research Informatics System Form...NOTES 14. ABSTRACT This project will prepare a related group of legacy data sets for addition to the Federal Interagency Traumatic Brain Injury

Discovery of common sequences absent in the human reference genome using pooled samples from next generation sequencing.

PubMed

Liu, Yu; Koyutürk, Mehmet; Maxwell, Sean; Xiang, Min; Veigl, Martina; Cooper, Richard S; Tayo, Bamidele O; Li, Li; LaFramboise, Thomas; Wang, Zhenghe; Zhu, Xiaofeng; Chance, Mark R

2014-08-16

Sequences up to several megabases in length have been found to be present in individual genomes but absent in the human reference genome. These sequences may be common in populations, and their absence in the reference genome may indicate rare variants in the genomes of individuals who served as donors for the human genome project. As the reference genome is used in probe design for microarray technology and mapping short reads in next generation sequencing (NGS), this missing sequence could be a source of bias in functional genomic studies and variant analysis. One End Anchor (OEA) and/or orphan reads from paired-end sequencing have been used to identify novel sequences that are absent in reference genome. However, there is no study to investigate the distribution, evolution and functionality of those sequences in human populations. To systematically identify and study the missing common sequences (micSeqs), we extended the previous method by pooling OEA reads from large number of individuals and applying strict filtering methods to remove false sequences. The pipeline was applied to data from phase 1 of the 1000 Genomes Project. We identified 309 micSeqs that are present in at least 1% of the human population, but absent in the reference genome. We confirmed 76% of these 309 micSeqs by comparison to other primate genomes, individual human genomes, and gene expression data. Furthermore, we randomly selected fifteen micSeqs and confirmed their presence using PCR validation in 38 additional individuals. Functional analysis using published RNA-seq and ChIP-seq data showed that eleven micSeqs are highly expressed in human brain and three micSeqs contain transcription factor (TF) binding regions, suggesting they are functional elements. In addition, the identified micSeqs are absent in non-primates and show dynamic acquisition during primate evolution culminating with most micSeqs being present in Africans, suggesting some micSeqs may be important sources of human diversity. 76% of micSeqs were confirmed by a comparative genomics approach. Fourteen micSeqs are expressed in human brain or contain TF binding regions. Some micSeqs are primate-specific, conserved and may play a role in the evolution of primates.

Communication and the primate brain: insights from neuroimaging studies in humans, chimpanzees and macaques.

PubMed

Wilson, Benjamin; Petkov, Christopher I

2011-04-01

Considerable knowledge is available on the neural substrates for speech and language from brain-imaging studies in humans, but until recently there was a lack of data for comparison from other animal species on the evolutionarily conserved brain regions that process species-specific communication signals. To obtain new insights into the relationship of the substrates for communication in primates, we compared the results from several neuroimaging studies in humans with those that have recently been obtained from macaque monkeys and chimpanzees. The recent work in humans challenges the longstanding notion of highly localized speech areas. As a result, the brain regions that have been identified in humans for speech and nonlinguistic voice processing show a striking general correspondence to how the brains of other primates analyze species-specific vocalizations or information in the voice, such as voice identity. The comparative neuroimaging work has begun to clarify evolutionary relationships in brain function, supporting the notion that the brain regions that process communication signals in the human brain arose from a precursor network of regions that is present in nonhuman primates and is used for processing species-specific vocalizations. We conclude by considering how the stage now seems to be set for comparative neurobiology to characterize the ancestral state of the network that evolved in humans to support language.

Art, energy, and the brain.

PubMed

Pepperell, Robert

2018-01-01

Recent years have seen a growing interest among neuroscientists and vision scientists in art and aesthetics, exemplifying a more general trend toward interdisciplinary integration in the arts, humanities, and sciences. However, true art-science integration remains a distant prospect due to fundamental differences in outlook and approach between disciplines. I consider two great challenges for any project designed to explain the role of the brain in art appreciation. First, scientists and artists need to identify common ground, common questions, and a shared motivation for inquiry. Second, the neuroscience of art must transcend its current goal of correlating brain functions to behavior and begin to explain the connection between activity in the brain and the phenomenology of art appreciation. I propose that both challenges can be tackled using an energy-based approach. The concept of "energy" is clearly of central importance to the physical sciences, and to neuroscience in particular. Meanwhile, energy is a concept that artists and art historians have consistently referred to when trying to articulate how artworks are made and appreciated. I survey the role of energy in art, philosophical and psychological aesthetics, and neuroscience, and suggest how this approach could help to further integrate art and neuroscience, and explain how brain activity contributes to aesthetic experience. © 2018 Elsevier B.V. All rights reserved.

Transferrin-tailored solid lipid nanoparticles as vectors for site-specific delivery of temozolomide to brain

NASA Astrophysics Data System (ADS)

Jain, Aviral; Singhai, Priyanka; Gurnany, Ekta; Updhayay, Satish; Mody, Nishi

2013-03-01

Blood-brain barrier restricts the uptake of many important hydrophilic drugs and limits their efficacy in the treatment of brain diseases because of the presence of tight junctions, high metabolic capacity, low pinocytic vesicular traffic, and efficient efflux mechanisms. In the present project, transferrin (Tf)-conjugated solid lipid nanoparticles (Tf-SLNs) were investigated for their ability to deliver temozolomide (TMZ) to the brain. SLNs were prepared by an ethanol injection method using hydrogenated soya phosphatidylcholine, triolein, cholesterol and distearoylphosphatidylethanolamine. Conjugation of SLNs with Tf was achieved by incubation of Tf with TMZ-loaded SLNs in the presence of 1-ethyl-3-(3-dimethylaminopropyl) carbodiimide hydrochloride in phosphate buffered saline (pH 7.4) as a cross linker. SLNs preparation were characterized for particle size, polydispersity index, zeta potential, surface morphology, percent drug entrapment efficiency, in vitro drug release, and hemolytic toxicity studies. In vitro cytotoxicity studies were performed on human cancer cell lines. The average size was found to be 221 ± 3.22 nm with entrapment efficiency of 69.83 ± 2.52 and 249 ± 2.61 nm with entrapment efficiency decreased to 64.21 ± 2.27 % for unconjugated SLNs and Tf-SLNs, respectively. Fluorescence studies revealed the enhanced uptake of Tf-SLNs in brain tissue compared with unconjugated SLNs.

Supervised dictionary learning for inferring concurrent brain networks.

PubMed

Zhao, Shijie; Han, Junwei; Lv, Jinglei; Jiang, Xi; Hu, Xintao; Zhao, Yu; Ge, Bao; Guo, Lei; Liu, Tianming

2015-10-01

Task-based fMRI (tfMRI) has been widely used to explore functional brain networks via predefined stimulus paradigm in the fMRI scan. Traditionally, the general linear model (GLM) has been a dominant approach to detect task-evoked networks. However, GLM focuses on task-evoked or event-evoked brain responses and possibly ignores the intrinsic brain functions. In comparison, dictionary learning and sparse coding methods have attracted much attention recently, and these methods have shown the promise of automatically and systematically decomposing fMRI signals into meaningful task-evoked and intrinsic concurrent networks. Nevertheless, two notable limitations of current data-driven dictionary learning method are that the prior knowledge of task paradigm is not sufficiently utilized and that the establishment of correspondences among dictionary atoms in different brains have been challenging. In this paper, we propose a novel supervised dictionary learning and sparse coding method for inferring functional networks from tfMRI data, which takes both of the advantages of model-driven method and data-driven method. The basic idea is to fix the task stimulus curves as predefined model-driven dictionary atoms and only optimize the other portion of data-driven dictionary atoms. Application of this novel methodology on the publicly available human connectome project (HCP) tfMRI datasets has achieved promising results.

Structural and functional correlates of visual field asymmetry in the human brain by diffusion kurtosis MRI and functional MRI.

PubMed

O'Connell, Caitlin; Ho, Leon C; Murphy, Matthew C; Conner, Ian P; Wollstein, Gadi; Cham, Rakie; Chan, Kevin C

2016-11-09

Human visual performance has been observed to show superiority in localized regions of the visual field across many classes of stimuli. However, the underlying neural mechanisms remain unclear. This study aims to determine whether the visual information processing in the human brain is dependent on the location of stimuli in the visual field and the corresponding neuroarchitecture using blood-oxygenation-level-dependent functional MRI (fMRI) and diffusion kurtosis MRI, respectively, in 15 healthy individuals at 3 T. In fMRI, visual stimulation to the lower hemifield showed stronger brain responses and larger brain activation volumes than the upper hemifield, indicative of the differential sensitivity of the human brain across the visual field. In diffusion kurtosis MRI, the brain regions mapping to the lower visual field showed higher mean kurtosis, but not fractional anisotropy or mean diffusivity compared with the upper visual field. These results suggested the different distributions of microstructural organization across visual field brain representations. There was also a strong positive relationship between diffusion kurtosis and fMRI responses in the lower field brain representations. In summary, this study suggested the structural and functional brain involvements in the asymmetry of visual field responses in humans, and is important to the neurophysiological and psychological understanding of human visual information processing.

Black-box Brain Experiments, Causal Mathematical Logic, and the Thermodynamics of Intelligence

NASA Astrophysics Data System (ADS)

Pissanetzky, Sergio; Lanzalaco, Felix

2013-12-01

Awareness of the possible existence of a yet-unknown principle of Physics that explains cognition and intelligence does exist in several projects of emulation, simulation, and replication of the human brain currently under way. Brain simulation projects define their success partly in terms of the emergence of non-explicitly programmed biophysical signals such as self-oscillation and spreading cortical waves. We propose that a recently discovered theory of Physics known as Causal Mathematical Logic (CML) that links intelligence with causality and entropy and explains intelligent behavior from first principles, is the missing link. We further propose the theory as a roadway to understanding more complex biophysical signals, and to explain the set of intelligence principles. The new theory applies to information considered as an entity by itself. The theory proposes that any device that processes information and exhibits intelligence must satisfy certain theoretical conditions irrespective of the substrate where it is being processed. The substrate can be the human brain, a part of it, a worm's brain, a motor protein that self-locomotes in response to its environment, a computer. Here, we propose to extend the causal theory to systems in Neuroscience, because of its ability to model complex systems without heuristic approximations, and to predict emerging signals of intelligence directly from the models. The theory predicts the existence of a large number of observables (or "signals"), all of which emerge and can be directly and mathematically calculated from non-explicitly programmed detailed causal models. This approach is aiming for a universal and predictive language for Neuroscience and AGI based on causality and entropy, detailed enough to describe the finest structures and signals of the brain, yet general enough to accommodate the versatility and wholeness of intelligence. Experiments are focused on a black-box as one of the devices described above of which both the input and the output are precisely known, but not the internal implementation. The same input is separately supplied to a causal virtual machine, and the calculated output is compared with the measured output. The virtual machine, described in a previous paper, is a computer implementation of CML, fixed for all experiments and unrelated to the device in the black box. If the two outputs are equivalent, then the experiment has quantitatively succeeded and conclusions can be drawn regarding details of the internal implementation of the device. Several small black-box experiments were successfully performed and demonstrated the emergence of non-explicitly programmed cognitive function in each case

Multimodal neural correlates of cognitive control in the Human Connectome Project.

PubMed

Lerman-Sinkoff, Dov B; Sui, Jing; Rachakonda, Srinivas; Kandala, Sridhar; Calhoun, Vince D; Barch, Deanna M

2017-12-01

Cognitive control is a construct that refers to the set of functions that enable decision-making and task performance through the representation of task states, goals, and rules. The neural correlates of cognitive control have been studied in humans using a wide variety of neuroimaging modalities, including structural MRI, resting-state fMRI, and task-based fMRI. The results from each of these modalities independently have implicated the involvement of a number of brain regions in cognitive control, including dorsal prefrontal cortex, and frontal parietal and cingulo-opercular brain networks. However, it is not clear how the results from a single modality relate to results in other modalities. Recent developments in multimodal image analysis methods provide an avenue for answering such questions and could yield more integrated models of the neural correlates of cognitive control. In this study, we used multiset canonical correlation analysis with joint independent component analysis (mCCA + jICA) to identify multimodal patterns of variation related to cognitive control. We used two independent cohorts of participants from the Human Connectome Project, each of which had data from four imaging modalities. We replicated the findings from the first cohort in the second cohort using both independent and predictive analyses. The independent analyses identified a component in each cohort that was highly similar to the other and significantly correlated with cognitive control performance. The replication by prediction analyses identified two independent components that were significantly correlated with cognitive control performance in the first cohort and significantly predictive of performance in the second cohort. These components identified positive relationships across the modalities in neural regions related to both dynamic and stable aspects of task control, including regions in both the frontal-parietal and cingulo-opercular networks, as well as regions hypothesized to be modulated by cognitive control signaling, such as visual cortex. Taken together, these results illustrate the potential utility of multi-modal analyses in identifying the neural correlates of cognitive control across different indicators of brain structure and function. Copyright © 2017 Elsevier Inc. All rights reserved.

The eye as metronome of the body.

PubMed

Lubkin, Virginia; Beizai, Pouneh; Sadun, Alfredo A

2002-01-01

Vision is much more than just resolving small objects. In fact, the eye sends visual information to the brain that is not consciously perceived. One such pathway entails visual information to the hypothalamus. The retinohypothalamic tract (RHT) mediates light entrainment of circadian rhythms. Retinofugal fibers project to several nuclei of the hypothalamus. These and further projections to the pineal via the sympathetic system provide the anatomical substrate for the neuro-endocrine control of diurnal and longer rhythms. Without the influence of light and dark, many rhythms desynchronize and exhibit free-running periods of approximately 24.2-24.9 hours in humans. This review will demonstrate the mechanism by which the RHT synchronizes circadian rhythms and the importance of preserving light perception in those persons with impending visual loss.

Modification of existing human motor memories is enabled by primary cortical processing during memory reactivation.

PubMed

Censor, Nitzan; Dimyan, Michael A; Cohen, Leonardo G

2010-09-14

One of the most challenging tasks of the brain is to constantly update the internal neural representations of existing memories. Animal studies have used invasive methods such as direct microfusion of protein inhibitors to designated brain areas, in order to study the neural mechanisms underlying modification of already existing memories after their reactivation during recall [1-4]. Because such interventions are not possible in humans, it is not known how these neural processes operate in the human brain. In a series of experiments we show here that when an existing human motor memory is reactivated during recall, modification of the memory is blocked by virtual lesion [5] of the related primary cortical human brain area. The virtual lesion was induced by noninvasive repetitive transcranial magnetic stimulation guided by a frameless stereotactic brain navigation system and each subject's brain image. The results demonstrate that primary cortical processing in the human brain interacting with pre-existing reactivated memory traces is critical for successful modification of the existing related memory. Modulation of reactivated memories by noninvasive cortical stimulation may have important implications for human memory research and have far-reaching clinical applications. Copyright © 2010 Elsevier Ltd. All rights reserved.

Human high intelligence is involved in spectral redshift of biophotonic activities in the brain

PubMed Central

Wang, Niting; Li, Zehua; Xiao, Fangyan; Dai, Jiapei

2016-01-01

Human beings hold higher intelligence than other animals on Earth; however, it is still unclear which brain properties might explain the underlying mechanisms. The brain is a major energy-consuming organ compared with other organs. Neural signal communications and information processing in neural circuits play an important role in the realization of various neural functions, whereas improvement in cognitive function is driven by the need for more effective communication that requires less energy. Combining the ultraweak biophoton imaging system (UBIS) with the biophoton spectral analysis device (BSAD), we found that glutamate-induced biophotonic activities and transmission in the brain, which has recently been demonstrated as a novel neural signal communication mechanism, present a spectral redshift from animals (in order of bullfrog, mouse, chicken, pig, and monkey) to humans, even up to a near-infrared wavelength (∼865 nm) in the human brain. This brain property may be a key biophysical basis for explaining high intelligence in humans because biophoton spectral redshift could be a more economical and effective measure of biophotonic signal communications and information processing in the human brain. PMID:27432962

Beyond sex differences: new approaches for thinking about variation in brain structure and function

PubMed Central

Joel, Daphna; Fausto-Sterling, Anne

2016-01-01

In the study of variation in brain structure and function that might relate to sex and gender, language matters because it frames our research questions and methods. In this article, we offer an approach to thinking about variation in brain structure and function that pulls us outside the sex differences formulation. We argue that the existence of differences between the brains of males and females does not unravel the relations between sex and the brain nor is it sufficient to characterize a population of brains. Such characterization is necessary for studying sex effects on the brain as well as for studying brain structure and function in general. Animal studies show that sex interacts with environmental, developmental and genetic factors to affect the brain. Studies of humans further suggest that human brains are better described as belonging to a single heterogeneous population rather than two distinct populations. We discuss the implications of these observations for studies of brain and behaviour in humans and in laboratory animals. We believe that studying sex effects in context and developing or adopting analytical methods that take into account the heterogeneity of the brain are crucial for the advancement of human health and well-being. PMID:26833844

Evidence of a Conserved Molecular Response to Selection for Increased Brain Size in Primates

PubMed Central

Harrison, Peter W.; Caravas, Jason A.; Raghanti, Mary Ann; Phillips, Kimberley A.; Mundy, Nicholas I.

2017-01-01

The adaptive significance of human brain evolution has been frequently studied through comparisons with other primates. However, the evolution of increased brain size is not restricted to the human lineage but is a general characteristic of primate evolution. Whether or not these independent episodes of increased brain size share a common genetic basis is unclear. We sequenced and de novo assembled the transcriptome from the neocortical tissue of the most highly encephalized nonhuman primate, the tufted capuchin monkey (Cebus apella). Using this novel data set, we conducted a genome-wide analysis of orthologous brain-expressed protein coding genes to identify evidence of conserved gene–phenotype associations and species-specific adaptations during three independent episodes of brain size increase. We identify a greater number of genes associated with either total brain mass or relative brain size across these six species than show species-specific accelerated rates of evolution in individual large-brained lineages. We test the robustness of these associations in an expanded data set of 13 species, through permutation tests and by analyzing how genome-wide patterns of substitution co-vary with brain size. Many of the genes targeted by selection during brain expansion have glutamatergic functions or roles in cell cycle dynamics. We also identify accelerated evolution in a number of individual capuchin genes whose human orthologs are associated with human neuropsychiatric disorders. These findings demonstrate the value of phenotypically informed genome analyses, and suggest at least some aspects of human brain evolution have occurred through conserved gene–phenotype associations. Understanding these commonalities is essential for distinguishing human-specific selection events from general trends in brain evolution. PMID:28391320

The Anterior Insular Cortex→Central Amygdala Glutamatergic Pathway Is Critical to Relapse after Contingency Management.

PubMed

Venniro, Marco; Caprioli, Daniele; Zhang, Michelle; Whitaker, Leslie R; Zhang, Shiliang; Warren, Brandon L; Cifani, Carlo; Marchant, Nathan J; Yizhar, Ofer; Bossert, Jennifer M; Chiamulera, Cristiano; Morales, Marisela; Shaham, Yavin

2017-10-11

Despite decades of research on neurobiological mechanisms of psychostimulant addiction, the only effective treatment for many addicts is contingency management, a behavioral treatment that uses alternative non-drug reward to maintain abstinence. However, when contingency management is discontinued, most addicts relapse to drug use. The brain mechanisms underlying relapse after cessation of contingency management are largely unknown, and, until recently, an animal model of this human condition did not exist. Here we used a novel rat model, in which the availability of a mutually exclusive palatable food maintains prolonged voluntary abstinence from intravenous methamphetamine self-administration, to demonstrate that the activation of monosynaptic glutamatergic projections from anterior insular cortex to central amygdala is critical to relapse after the cessation of contingency management. We identified the anterior insular cortex-to-central amygdala projection as a new addiction- and motivation-related projection and a potential target for relapse prevention. Published by Elsevier Inc.

Loss of Brain Aerobic Glycolysis in Normal Human Aging.

PubMed

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

2017-08-01

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

Human brain networks function in connectome-specific harmonic waves.

PubMed

Atasoy, Selen; Donnelly, Isaac; Pearson, Joel

2016-01-21

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

Red-backed vole brain promotes highly efficient in vitro amplification of abnormal prion protein from macaque and human brains infected with variant Creutzfeldt-Jakob disease agent.

USGS Publications Warehouse

Nemecek, Julie; Nag, Nabanita; Carlson, Christina M.; Schneider, Jay R.; Heisey, Dennis M.; Johnson, Christopher J.; Asher, David M.; Gregori, Luisa

2013-01-01

Rapid antemortem tests to detect individuals with transmissible spongiform encephalopathies (TSE) would contribute to public health. We investigated a technique known as protein misfolding cyclic amplification (PMCA) to amplify abnormal prion protein (PrPTSE) from highly diluted variant Creutzfeldt-Jakob disease (vCJD)-infected human and macaque brain homogenates, seeking to improve the rapid detection of PrPTSE in tissues and blood. Macaque vCJD PrPTSE did not amplify using normal macaque brain homogenate as substrate (intraspecies PMCA). Next, we tested interspecies PMCA with normal brain homogenate of the southern red-backed vole (RBV), a close relative of the bank vole, seeded with macaque vCJD PrPTSE. The RBV has a natural polymorphism at residue 170 of the PrP-encoding gene (N/N, S/S, and S/N). We investigated the effect of this polymorphism on amplification of human and macaque vCJD PrPTSE. Meadow vole brain (170N/N PrP genotype) was also included in the panel of substrates tested. Both humans and macaques have the same 170S/S PrP genotype. Macaque PrPTSE was best amplified with RBV 170S/S brain, although 170N/N and 170S/N were also competent substrates, while meadow vole brain was a poor substrate. In contrast, human PrPTSE demonstrated a striking narrow selectivity for PMCA substrate and was successfully amplified only with RBV 170S/S brain. These observations suggest that macaque PrPTSE was more permissive than human PrPTSE in selecting the competent RBV substrate. RBV 170S/S brain was used to assess the sensitivity of PMCA with PrPTSE from brains of humans and macaques with vCJD. PrPTSE signals were reproducibly detected by Western blot in dilutions through 10-12 of vCJD-infected 10% brain homogenates. This is the first report showing PrPTSE from vCJD-infected human and macaque brains efficiently amplified with RBV brain as the substrate. Based on our estimates, PMCA showed a sensitivity that might be sufficient to detect PrPTSE in vCJD-infected human and macaque blood.

A multi-pathway hypothesis for human visual fear signaling

PubMed Central

Silverstein, David N.; Ingvar, Martin

2015-01-01

A hypothesis is proposed for five visual fear signaling pathways in humans, based on an analysis of anatomical connectivity from primate studies and human functional connectvity and tractography from brain imaging studies. Earlier work has identified possible subcortical and cortical fear pathways known as the “low road” and “high road,” which arrive at the amygdala independently. In addition to a subcortical pathway, we propose four cortical signaling pathways in humans along the visual ventral stream. All four of these traverse through the LGN to the visual cortex (VC) and branching off at the inferior temporal area, with one projection directly to the amygdala; another traversing the orbitofrontal cortex; and two others passing through the parietal and then prefrontal cortex, one excitatory pathway via the ventral-medial area and one regulatory pathway via the ventral-lateral area. These pathways have progressively longer propagation latencies and may have progressively evolved with brain development to take advantage of higher-level processing. Using the anatomical path lengths and latency estimates for each of these five pathways, predictions are made for the relative processing times at selective ROIs and arrival at the amygdala, based on the presentation of a fear-relevant visual stimulus. Partial verification of the temporal dynamics of this hypothesis might be accomplished using experimental MEG analysis. Possible experimental protocols are suggested. PMID:26379513

Quantitative Imaging of Energy Expenditure in Human Brain

PubMed Central

Zhu, Xiao-Hong; Qiao, Hongyan; Du, Fei; Xiong, Qiang; Liu, Xiao; Zhang, Xiaoliang; Ugurbil, Kamil; Chen, Wei

2012-01-01

Despite the essential role of the brain energy generated from ATP hydrolysis in supporting cortical neuronal activity and brain function, it is challenging to noninvasively image and directly quantify the energy expenditure in the human brain. In this study, we applied an advanced in vivo 31P MRS imaging approach to obtain regional cerebral metabolic rates of high-energy phosphate reactions catalyzed by ATPase (CMRATPase) and creatine kinase (CMRCK), and to determine CMRATPase and CMRCK in pure grey mater (GM) and white mater (WM), respectively. It was found that both ATPase and CK rates are three times higher in GM than WM; and CMRCK is seven times higher than CMRATPase in GM and WM. Among the total brain ATP consumption in the human cortical GM and WM, 77% of them are used by GM in which approximately 96% is by neurons. A single cortical neuron utilizes approximately 4.7 billion ATPs per second in a resting human brain. This study demonstrates the unique utility of in vivo 31P MRS imaging modality for direct imaging of brain energy generated from ATP hydrolysis, and provides new insights into the human brain energetics and its role in supporting neuronal activity and brain function. PMID:22487547

Characteristics of allelic gene expression in human brain cells from single-cell RNA-seq data analysis.

PubMed

Zhao, Dejian; Lin, Mingyan; Pedrosa, Erika; Lachman, Herbert M; Zheng, Deyou

2017-11-10

Monoallelic expression of autosomal genes has been implicated in human psychiatric disorders. However, there is a paucity of allelic expression studies in human brain cells at the single cell and genome wide levels. In this report, we reanalyzed a previously published single-cell RNA-seq dataset from several postmortem human brains and observed pervasive monoallelic expression in individual cells, largely in a random manner. Examining single nucleotide variants with a predicted functional disruption, we found that the "damaged" alleles were overall expressed in fewer brain cells than their counterparts, and at a lower level in cells where their expression was detected. We also identified many brain cell type-specific monoallelically expressed genes. Interestingly, many of these cell type-specific monoallelically expressed genes were enriched for functions important for those brain cell types. In addition, function analysis showed that genes displaying monoallelic expression and correlated expression across neuronal cells from different individual brains were implicated in the regulation of synaptic function. Our findings suggest that monoallelic gene expression is prevalent in human brain cells, which may play a role in generating cellular identity and neuronal diversity and thus increasing the complexity and diversity of brain cell functions.

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

ERIC Educational Resources Information Center

Miller, Geoffrey F.; Penke, Lars

2007-01-01

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

Total brain death: a reply to Alan Shewmon.

PubMed

Lee, Patrick; GriseZ, Germain

2012-06-01

D. Alan Shewmon has advanced a well-documented challenge to the widely accepted total brain death criterion for death of the human being. We show that Shewmon’s argument against this criterion is unsound, though he does refute the standard argument for that criterion. We advance a distinct argument for the total brain death criterion and answer likely objections. Since human beings are rational animals--sentient organisms of a specific type--the loss of the radical capacity for sentience (the capacity to sense or to develop the capacity to sense) involves a substantial change, the passing away of the human organism. In human beings total brain death involves the complete loss of the radical capacity for sentience, and so in human beings total brain death is death.

Multidimensional brain activity dictated by winner-take-all mechanisms.

PubMed

Tozzi, Arturo; Peters, James F

2018-06-21

A novel demon-based architecture is introduced to elucidate brain functions such as pattern recognition during human perception and mental interpretation of visual scenes. Starting from the topological concepts of invariance and persistence, we introduce a Selfridge pandemonium variant of brain activity that takes into account a novel feature, namely, demons that recognize short straight-line segments, curved lines and scene shapes, such as shape interior, density and texture. Low-level representations of objects can be mapped to higher-level views (our mental interpretations): a series of transformations can be gradually applied to a pattern in a visual scene, without affecting its invariant properties. This makes it possible to construct a symbolic multi-dimensional representation of the environment. These representations can be projected continuously to an object that we have seen and continue to see, thanks to the mapping from shapes in our memory to shapes in Euclidean space. Although perceived shapes are 3-dimensional (plus time), the evaluation of shape features (volume, color, contour, closeness, texture, and so on) leads to n-dimensional brain landscapes. Here we discuss the advantages of our parallel, hierarchical model in pattern recognition, computer vision and biological nervous system's evolution. Copyright © 2018 Elsevier B.V. All rights reserved.

A Dictionary Learning Approach for Signal Sampling in Task-Based fMRI for Reduction of Big Data

PubMed Central

Ge, Bao; Li, Xiang; Jiang, Xi; Sun, Yifei; Liu, Tianming

2018-01-01

The exponential growth of fMRI big data offers researchers an unprecedented opportunity to explore functional brain networks. However, this opportunity has not been fully explored yet due to the lack of effective and efficient tools for handling such fMRI big data. One major challenge is that computing capabilities still lag behind the growth of large-scale fMRI databases, e.g., it takes many days to perform dictionary learning and sparse coding of whole-brain fMRI data for an fMRI database of average size. Therefore, how to reduce the data size but without losing important information becomes a more and more pressing issue. To address this problem, we propose a signal sampling approach for significant fMRI data reduction before performing structurally-guided dictionary learning and sparse coding of whole brain's fMRI data. We compared the proposed structurally guided sampling method with no sampling, random sampling and uniform sampling schemes, and experiments on the Human Connectome Project (HCP) task fMRI data demonstrated that the proposed method can achieve more than 15 times speed-up without sacrificing the accuracy in identifying task-evoked functional brain networks. PMID:29706880

A Dictionary Learning Approach for Signal Sampling in Task-Based fMRI for Reduction of Big Data.

PubMed

Ge, Bao; Li, Xiang; Jiang, Xi; Sun, Yifei; Liu, Tianming

2018-01-01

The exponential growth of fMRI big data offers researchers an unprecedented opportunity to explore functional brain networks. However, this opportunity has not been fully explored yet due to the lack of effective and efficient tools for handling such fMRI big data. One major challenge is that computing capabilities still lag behind the growth of large-scale fMRI databases, e.g., it takes many days to perform dictionary learning and sparse coding of whole-brain fMRI data for an fMRI database of average size. Therefore, how to reduce the data size but without losing important information becomes a more and more pressing issue. To address this problem, we propose a signal sampling approach for significant fMRI data reduction before performing structurally-guided dictionary learning and sparse coding of whole brain's fMRI data. We compared the proposed structurally guided sampling method with no sampling, random sampling and uniform sampling schemes, and experiments on the Human Connectome Project (HCP) task fMRI data demonstrated that the proposed method can achieve more than 15 times speed-up without sacrificing the accuracy in identifying task-evoked functional brain networks.

Function in the Human Connectome: Task-fMRI and Individual Differences in Behavior

PubMed Central

Barch, Deanna M.; Burgess, Gregory C.; Harms, Michael P.; Petersen, Steven E.; Schlaggar, Bradley L.; Corbetta, Maurizio; Glasser, Matthew F.; Curtiss, Sandra; Dixit, Sachin; Feldt, Cindy; Nolan, Dan; Bryant, Edward; Hartley, Tucker; Footer, Owen; Bjork, James M.; Poldrack, Russ; Smith, Steve; Johansen-Berg, Heidi; Snyder, Abraham Z.; Van Essen, David C.

2014-01-01

The primary goal of the Human Connectome Project (HCP) is to delineate the typical patterns of structural and functional connectivity in the healthy adult human brain. However, we know that there are important individual differences in such patterns of connectivity, with evidence that this variability is associated with alterations in important cognitive and behavioral variables that affect real world function. The HCP data will be a critical stepping-off point for future studies that will examine how variation in human structural and functional connectivity play a role in adult and pediatric neurological and psychiatric disorders that account for a huge amount of public health resources. Thus, the HCP is collecting behavioral measures of a range of motor, sensory, cognitive and emotional processes that will delineate a core set of functions relevant to understanding the relationship between brain connectivity and human behavior. In addition, the HCP is using task-fMRI (tfMRI) to help delineate the relationships between individual differences in the neurobiological substrates of mental processing and both functional and structural connectivity, as well as to help characterize and validate the connectivity analyses to be conducted on the structural and functional connectivity data. This paper describes the logic and rationale behind the development of the behavioral, individual difference, and tfMRI batteries and provides preliminary data on the patterns of activation associated with each of the fMRI tasks, at both a group and individual level. PMID:23684877

Disrupted white matter connectivity underlying developmental dyslexia: A machine learning approach.

PubMed

Cui, Zaixu; Xia, Zhichao; Su, Mengmeng; Shu, Hua; Gong, Gaolang

2016-04-01

Developmental dyslexia has been hypothesized to result from multiple causes and exhibit multiple manifestations, implying a distributed multidimensional effect on human brain. The disruption of specific white-matter (WM) tracts/regions has been observed in dyslexic children. However, it remains unknown if developmental dyslexia affects the human brain WM in a multidimensional manner. Being a natural tool for evaluating this hypothesis, the multivariate machine learning approach was applied in this study to compare 28 school-aged dyslexic children with 33 age-matched controls. Structural magnetic resonance imaging (MRI) and diffusion tensor imaging were acquired to extract five multitype WM features at a regional level: white matter volume, fractional anisotropy, mean diffusivity, axial diffusivity, and radial diffusivity. A linear support vector machine (LSVM) classifier achieved an accuracy of 83.61% using these MRI features to distinguish dyslexic children from controls. Notably, the most discriminative features that contributed to the classification were primarily associated with WM regions within the putative reading network/system (e.g., the superior longitudinal fasciculus, inferior fronto-occipital fasciculus, thalamocortical projections, and corpus callosum), the limbic system (e.g., the cingulum and fornix), and the motor system (e.g., the cerebellar peduncle, corona radiata, and corticospinal tract). These results were well replicated using a logistic regression classifier. These findings provided direct evidence supporting a multidimensional effect of developmental dyslexia on WM connectivity of human brain, and highlighted the involvement of WM tracts/regions beyond the well-recognized reading system in dyslexia. Finally, the discriminating results demonstrated a potential of WM neuroimaging features as imaging markers for identifying dyslexic individuals. © 2016 Wiley Periodicals, Inc.

A Direct Brain-to-Brain Interface in Humans

PubMed Central

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

2014-01-01

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

Cloning and sequence analysis of the human brain beta-adrenergic receptor. Evolutionary relationship to rodent and avian beta-receptors and porcine muscarinic receptors.

PubMed

Chung, F Z; Lentes, K U; Gocayne, J; Fitzgerald, M; Robinson, D; Kerlavage, A R; Fraser, C M; Venter, J C

1987-01-26

Two cDNA clones, lambda-CLFV-108 and lambda-CLFV-119, encoding for the beta-adrenergic receptor, have been isolated from a human brain stem cDNA library. One human genomic clone, LCV-517 (20 kb), was characterized by restriction mapping and partial sequencing. The human brain beta-receptor consists of 413 amino acids with a calculated Mr of 46480. The gene contains three potential glucocorticoid receptor-binding sites. The beta-receptor expressed in human brain was homology with rodent (88%) and avian (52%) beta-receptors and with porcine muscarinic cholinergic receptors (31%), supporting our proposal [(1984) Proc. Natl. Acad. Sci. USA 81, 272 276] that adrenergic and muscarinic cholinergic receptors are structurally related. This represents the first cloning of a neurotransmitter receptor gene from human brain.

An Integrated Self-Aware Cognitive Architecture

DTIC Science & Technology

2008-03-01

human-like cognitive growth. Our approach is inspired by studies of the human brain -mind: in particular, by theoretical models of representations of...agency in the higher associative human brain areas. This feature (a theory of mind including representations of one’s self) allows the system to...self-aware cognition that we believe is necessary for human-like cognitive growth. Our approach is inspired by studies of the human brain -mind: in

BECon: a tool for interpreting DNA methylation findings from blood in the context of brain.

PubMed

Edgar, R D; Jones, M J; Meaney, M J; Turecki, G; Kobor, M S

2017-08-01

Tissue differences are one of the largest contributors to variability in the human DNA methylome. Despite the tissue-specific nature of DNA methylation, the inaccessibility of human brain samples necessitates the frequent use of surrogate tissues such as blood, in studies of associations between DNA methylation and brain function and health. Results from studies of surrogate tissues in humans are difficult to interpret in this context, as the connection between blood-brain DNA methylation is tenuous and not well-documented. Here, we aimed to provide a resource to the community to aid interpretation of blood-based DNA methylation results in the context of brain tissue. We used paired samples from 16 individuals from three brain regions and whole blood, run on the Illumina 450 K Human Methylation Array to quantify the concordance of DNA methylation between tissues. From these data, we have made available metrics on: the variability of cytosine-phosphate-guanine dinucleotides (CpGs) in our blood and brain samples, the concordance of CpGs between blood and brain, and estimations of how strongly a CpG is affected by cell composition in both blood and brain through the web application BECon (Blood-Brain Epigenetic Concordance; https://redgar598.shinyapps.io/BECon/). We anticipate that BECon will enable biological interpretation of blood-based human DNA methylation results, in the context of brain.

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

PubMed Central

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

2013-01-01

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

Bovine brain ribonuclease is the functional homolog of human ribonuclease 1.

PubMed

Eller, Chelcie H; Lomax, Jo E; Raines, Ronald T

2014-09-19

Mounting evidence suggests that human pancreatic ribonuclease (RNase 1) plays important roles in vivo, ranging from regulating blood clotting and inflammation to directly counteracting tumorigenic cells. Understanding these putative roles has been pursued with continual comparisons of human RNase 1 to bovine RNase A, an enzyme that appears to function primarily in the ruminant gut. Our results imply a different physiology for human RNase 1. We demonstrate distinct functional differences between human RNase 1 and bovine RNase A. Moreover, we characterize another RNase 1 homolog, bovine brain ribonuclease, and find pronounced similarities between that enzyme and human RNase 1. We report that human RNase 1 and bovine brain ribonuclease share high catalytic activity against double-stranded RNA substrates, a rare quality among ribonucleases. Both human RNase 1 and bovine brain RNase are readily endocytosed by mammalian cells, aided by tight interactions with cell surface glycans. Finally, we show that both human RNase 1 and bovine brain RNase are secreted from endothelial cells in a regulated manner, implying a potential role in vascular homeostasis. Our results suggest that brain ribonuclease, not RNase A, is the true bovine homolog of human RNase 1, and provide fundamental insight into the ancestral roles and functional adaptations of RNase 1 in mammals. © 2014 by The American Society for Biochemistry and Molecular Biology, Inc.

A theory of marks and mind: the effect of notational systems on hominid brain evolution and child development with an emphasis on exchanges between mothers and children.

PubMed

Sheridan, Susan Rich

2005-01-01

A model of human language requires a theory of meaningful marks. Humans are the only species who use marks to think. A theory of marks identifies children's scribbles as significant behavior, while hypothesizing the importance of rotational systems to hominid brain evolution. By recognizing the importance of children's scribbles and drawings in developmental terms as well as in evolutionary terms, a marks-based rather than a predominantly speech-based theory of the human brain, language, and consciousness emerges. Combined research in anthropology, primatology, art history, neurology, child development (including research with deaf and blind children), gender studies and literacy suggests the importance of notational systems to human language, revealing the importance of mother/child interactions around marks and sounds to the development of an expressive, communicative, symbolic human brain. An understanding of human language is enriched by identifying marks carved on bone 1.9 million years ago as observational lunar calendar-keeping, pushing proto-literacy back dramatically. Neurologically, children recapitulate the meaningful marks of early hominins when they scribble and draw, reminding us that literacy belongs to humankind's earliest history. Even more than speech, such meaningful marks played - and continue to play - decisive roles in human brain evolution. The hominid brain required a model for integrative, transformative neural transfer. The research strongly suggests that humankind's multiple literacies (art, literature, scientific writing, mathematics and music) depended upon dyadic exchanges between hominid mothers and children, and that this exchange and sharing of visuo-spatial information drove the elaboration of human speech in terms of syntax, grammar and vocabulary. The human brain was spatial before it was linguistic. The child scribbles and draws before it speaks or writes. Children babble and scribble within the first two years of life. Hands and mouths are proximal on the sensory-motor cortex. Gestures accompany speech. Illiterate brains mis-pronounce nonsense sounds. Literate brains do not. Written language (work of the hands) enhances spoken language (work of the mouth). Until brain scans map the neurological links between human gesture, speech and marks in the context of mother/caregiver/child interactions, and research with literate and illiterate brains document even more precisely the long-term differences between these brains, the evolutionary pressure of marks on especially flexible maternal and infant brain tissue that occurred 1.9 million years, radically changing primate brain capabilities, requires an integrated theory of marks and mind.

Transcriptional landscape of the prenatal human brain.

PubMed

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

2014-04-10

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

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

PubMed Central

Barrett, Lisa Feldman; Satpute, Ajay

2013-01-01

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. PMID:23352202

An animal-to-human scaling law for blast-induced traumatic brain injury risk assessment.

PubMed

Jean, Aurélie; Nyein, Michelle K; Zheng, James Q; Moore, David F; Joannopoulos, John D; Radovitzky, Raúl

2014-10-28

Despite recent efforts to understand blast effects on the human brain, there are still no widely accepted injury criteria for humans. Recent animal studies have resulted in important advances in the understanding of brain injury due to intense dynamic loads. However, the applicability of animal brain injury results to humans remains uncertain. Here, we use advanced computational models to derive a scaling law relating blast wave intensity to the mechanical response of brain tissue across species. Detailed simulations of blast effects on the brain are conducted for different mammals using image-based biofidelic models. The intensity of the stress waves computed for different external blast conditions is compared across species. It is found that mass scaling, which successfully estimates blast tolerance of the thorax, fails to capture the brain mechanical response to blast across mammals. Instead, we show that an appropriate scaling variable must account for the mass of protective tissues relative to the brain, as well as their acoustic impedance. Peak stresses transmitted to the brain tissue by the blast are then shown to be a power function of the scaling parameter for a range of blast conditions relevant to TBI. In particular, it is found that human brain vulnerability to blast is higher than for any other mammalian species, which is in distinct contrast to previously proposed scaling laws based on body or brain mass. An application of the scaling law to recent experiments on rabbits furnishes the first physics-based injury estimate for blast-induced TBI in humans.

Structural and Functional Correlates of Visual Field Asymmetry in the Human Brain by Diffusion Kurtosis MRI and Functional MRI

PubMed Central

O’Connell, Caitlin; Ho, Leon C.; Murphy, Matthew C.; Conner, Ian P.; Wollstein, Gadi; Cham, Rakie; Chan, Kevin C.

2016-01-01

Human visual performance has been observed to exhibit superiority in localized regions of the visual field across many classes of stimuli. However, the underlying neural mechanisms remain unclear. This study aims to determine if the visual information processing in the human brain is dependent on the location of stimuli in the visual field and the corresponding neuroarchitecture using blood-oxygenation-level-dependent functional MRI (fMRI) and diffusion kurtosis MRI (DKI), respectively in 15 healthy individuals at 3 Tesla. In fMRI, visual stimulation to the lower hemifield showed stronger brain responses and larger brain activation volumes than the upper hemifield, indicative of the differential sensitivity of the human brain across the visual field. In DKI, the brain regions mapping to the lower visual field exhibited higher mean kurtosis but not fractional anisotropy or mean diffusivity when compared to the upper visual field. These results suggested the different distributions of microstructural organization across visual field brain representations. There was also a strong positive relationship between diffusion kurtosis and fMRI responses in the lower field brain representations. In summary, this study suggested the structural and functional brain involvements in the asymmetry of visual field responses in humans, and is important to the neurophysiological and psychological understanding of human visual information processing. PMID:27631541

Development of a Human Neurovascular Unit Organotypic Systems Model of Early Brain Development

EPA Science Inventory

The inability to model human brain and blood-brain barrier development in vitro poses a major challenge in studies of how chemicals impact early neurogenic periods. During human development, disruption of thyroid hormone (TH) signaling is related to adverse morphological effects ...

Comparative Methylome Analyses Identify Epigenetic Regulatory Loci of Human Brain Evolution

PubMed Central

Mendizabal, Isabel; Shi, Lei; Keller, Thomas E.; Konopka, Genevieve; Preuss, Todd M.; Hsieh, Tzung-Fu; Hu, Enzhi; Zhang, Zhe; Su, Bing; Yi, Soojin V.

2016-01-01

How do epigenetic modifications change across species and how do these modifications affect evolution? These are fundamental questions at the forefront of our evolutionary epigenomic understanding. Our previous work investigated human and chimpanzee brain methylomes, but it was limited by the lack of outgroup data which is critical for comparative (epi)genomic studies. Here, we compared whole genome DNA methylation maps from brains of humans, chimpanzees and also rhesus macaques (outgroup) to elucidate DNA methylation changes during human brain evolution. Moreover, we validated that our approach is highly robust by further examining 38 human-specific DMRs using targeted deep genomic and bisulfite sequencing in an independent panel of 37 individuals from five primate species. Our unbiased genome-scan identified human brain differentially methylated regions (DMRs), irrespective of their associations with annotated genes. Remarkably, over half of the newly identified DMRs locate in intergenic regions or gene bodies. Nevertheless, their regulatory potential is on par with those of promoter DMRs. An intriguing observation is that DMRs are enriched in active chromatin loops, suggesting human-specific evolutionary remodeling at a higher-order chromatin structure. These findings indicate that there is substantial reprogramming of epigenomic landscapes during human brain evolution involving noncoding regions. PMID:27563052

Linking brains and brawn: exercise and the evolution of human neurobiology.

PubMed

Raichlen, David A; Polk, John D

2013-01-07

The hunting and gathering lifestyle adopted by human ancestors around 2 Ma required a large increase in aerobic activity. High levels of physical activity altered the shape of the human body, enabling access to new food resources (e.g. animal protein) in a changing environment. Recent experimental work provides strong evidence that both acute bouts of exercise and long-term exercise training increase the size of brain components and improve cognitive performance in humans and other taxa. However, to date, researchers have not explored the possibility that the increases in aerobic capacity and physical activity that occurred during human evolution directly influenced the human brain. Here, we hypothesize that proximate mechanisms linking physical activity and neurobiology in living species may help to explain changes in brain size and cognitive function during human evolution. We review evidence that selection acting on endurance increased baseline neurotrophin and growth factor signalling (compounds responsible for both brain growth and for metabolic regulation during exercise) in some mammals, which in turn led to increased overall brain growth and development. This hypothesis suggests that a significant portion of human neurobiology evolved due to selection acting on features unrelated to cognitive performance.

Midsagittal Brain Variation among Non-Human Primates: Insights into Evolutionary Expansion of the Human Precuneus.

PubMed

Pereira-Pedro, Ana Sofia; Rilling, James K; Chen, Xu; Preuss, Todd M; Bruner, Emiliano

2017-01-01

The precuneus is a major element of the superior parietal lobule, positioned on the medial side of the hemisphere and reaching the dorsal surface of the brain. It is a crucial functional region for visuospatial integration, visual imagery, and body coordination. Previously, we argued that the precuneus expanded in recent human evolution, based on a combination of paleontological, comparative, and intraspecific evidence from fossil and modern human endocasts as well as from human and chimpanzee brains. The longitudinal proportions of this region are a major source of anatomical variation among adult humans and, being much larger in Homo sapiens, is the main characteristic differentiating human midsagittal brain morphology from that of our closest living primate relative, the chimpanzee. In the current shape analysis, we examine precuneus variation in non-human primates through landmark-based models, to evaluate the general pattern of variability in non-human primates, and to test whether precuneus proportions are influenced by allometric effects of brain size. Results show that precuneus proportions do not covary with brain size, and that the main difference between monkeys and apes involves a vertical expansion of the frontal and occipital regions in apes. Such differences might reflect differences in brain proportions or differences in cranial architecture. In this sample, precuneus variation is apparently not influenced by phylogenetic or allometric factors, but does vary consistently within species, at least in chimpanzees and macaques. This result further supports the hypothesis that precuneus expansion in modern humans is not merely a consequence of increasing brain size or of allometric scaling, but rather represents a species-specific morphological change in our lineage. © 2017 S. Karger AG, Basel.

On initial Brain Activity Mapping of episodic and semantic memory code in the hippocampus.

PubMed

Tsien, Joe Z; Li, Meng; Osan, Remus; Chen, Guifen; Lin, Longian; Wang, Phillip Lei; Frey, Sabine; Frey, Julietta; Zhu, Dajiang; Liu, Tianming; Zhao, Fang; Kuang, Hui

2013-10-01

It has been widely recognized that the understanding of the brain code would require large-scale recording and decoding of brain activity patterns. In 2007 with support from Georgia Research Alliance, we have launched the Brain Decoding Project Initiative with the basic idea which is now similarly advocated by BRAIN project or Brain Activity Map proposal. As the planning of the BRAIN project is currently underway, we share our insights and lessons from our efforts in mapping real-time episodic memory traces in the hippocampus of freely behaving mice. We show that appropriate large-scale statistical methods are essential to decipher and measure real-time memory traces and neural dynamics. We also provide an example of how the carefully designed, sometime thinking-outside-the-box, behavioral paradigms can be highly instrumental to the unraveling of memory-coding cell assembly organizing principle in the hippocampus. Our observations to date have led us to conclude that the specific-to-general categorical and combinatorial feature-coding cell assembly mechanism represents an emergent property for enabling the neural networks to generate and organize not only episodic memory, but also semantic knowledge and imagination. Copyright © 2013 The Authors. Published by Elsevier Inc. All rights reserved.

On Initial Brain Activity Mapping of Associative Memory Code in the Hippocampus

PubMed Central

Tsien, Joe Z.; Li, Meng; Osan, Remus; Chen, Guifen; Lin, Longian; Lei Wang, Phillip; Frey, Sabine; Frey, Julietta; Zhu, Dajiang; Liu, Tianming; Zhao, Fang; Kuang, Hui

2013-01-01

It has been widely recognized that the understanding of the brain code would require large-scale recording and decoding of brain activity patterns. In 2007 with support from Georgia Research Alliance, we have launched the Brain Decoding Project Initiative with the basic idea which is now similarly advocated by BRAIN project or Brain Activity Map proposal. As the planning of the BRAIN project is currently underway, we share our insights and lessons from our efforts in mapping real-time episodic memory traces in the hippocampus of freely behaving mice. We show that appropriate large-scale statistical methods are essential to decipher and measure real-time memory traces and neural dynamics. We also provide an example of how the carefully designed, sometime thinking-outside-the-box, behavioral paradigms can be highly instrumental to the unraveling of memory-coding cell assembly organizing principle in the hippocampus. Our observations to date have led us to conclude that the specific-to-general categorical and combinatorial feature-coding cell assembly mechanism represents an emergent property for enabling the neural networks to generate and organize not only episodic memory, but also semantic knowledge and imagination. PMID:23838072

Towards Tunable Consensus Clustering for Studying Functional Brain Connectivity During Affective Processing.

PubMed

Liu, Chao; Abu-Jamous, Basel; Brattico, Elvira; Nandi, Asoke K

2017-03-01

In the past decades, neuroimaging of humans has gained a position of status within neuroscience, and data-driven approaches and functional connectivity analyses of functional magnetic resonance imaging (fMRI) data are increasingly favored to depict the complex architecture of human brains. However, the reliability of these findings is jeopardized by too many analysis methods and sometimes too few samples used, which leads to discord among researchers. We propose a tunable consensus clustering paradigm that aims at overcoming the clustering methods selection problem as well as reliability issues in neuroimaging by means of first applying several analysis methods (three in this study) on multiple datasets and then integrating the clustering results. To validate the method, we applied it to a complex fMRI experiment involving affective processing of hundreds of music clips. We found that brain structures related to visual, reward, and auditory processing have intrinsic spatial patterns of coherent neuroactivity during affective processing. The comparisons between the results obtained from our method and those from each individual clustering algorithm demonstrate that our paradigm has notable advantages over traditional single clustering algorithms in being able to evidence robust connectivity patterns even with complex neuroimaging data involving a variety of stimuli and affective evaluations of them. The consensus clustering method is implemented in the R package "UNCLES" available on http://cran.r-project.org/web/packages/UNCLES/index.html .

Decoding Saccadic Directions Using Epidural ECoG in Non-Human Primates.

PubMed

Lee, Jeyeon; Choi, Hoseok; Lee, Seho; Cho, Baek Hwan; Ahn, Kyoung Ha; Kim, In Young; Lee, Kyoung Min; Jang, Dong Pyo

2017-08-01

A brain-computer interface (BCI) can be used to restore some communication as an alternative interface for patients suffering from locked-in syndrome. However, most BCI systems are based on SSVEP, P300, or motor imagery, and a diversity of BCI protocols would be needed for various types of patients. In this paper, we trained the choice saccade (CS) task in 2 non-human primate monkeys and recorded the brain signal using an epidural electrocorticogram (eECoG) to predict eye movement direction. We successfully predicted the direction of the upcoming eye movement using a support vector machine (SVM) with the brain signals after the directional cue onset and before the saccade execution. The mean accuracies were 80% for 2 directions and 43% for 4 directions. We also quantified the spatial-spectro-temporal contribution ratio using SVM recursive feature elimination (RFE). The channels over the frontal eye field (FEF), supplementary eye field (SEF), and superior parietal lobule (SPL) area were dominantly used for classification. The α-band in the spectral domain and the time bins just after the directional cue onset and just before the saccadic execution were mainly useful for prediction. A saccade based BCI paradigm can be projected in the 2D space, and will hopefully provide an intuitive and convenient communication platform for users. © 2017 The Korean Academy of Medical Sciences.

Identification of the Transcriptional Targets of FOXP2, a Gene Linked to Speech and Language, in Developing Human Brain

PubMed Central

Spiteri, Elizabeth ; Konopka, Genevieve ; Coppola, Giovanni ; Bomar, Jamee ; Oldham, Michael ; Ou, Jing ; Vernes, Sonja C. ; Fisher, Simon E. ; Ren, Bing ; Geschwind, Daniel H. 

2007-01-01

Mutations in FOXP2, a member of the forkhead family of transcription factor genes, are the only known cause of developmental speech and language disorders in humans. To date, there are no known targets of human FOXP2 in the nervous system. The identification of FOXP2 targets in the developing human brain, therefore, provides a unique tool with which to explore the development of human language and speech. Here, we define FOXP2 targets in human basal ganglia (BG) and inferior frontal cortex (IFC) by use of chromatin immunoprecipitation followed by microarray analysis (ChIP-chip) and validate the functional regulation of targets in vitro. ChIP-chip identified 285 FOXP2 targets in fetal human brain; statistically significant overlap of targets in BG and IFC indicates a core set of 34 transcriptional targets of FOXP2. We identified targets specific to IFC or BG that were not observed in lung, suggesting important regional and tissue differences in FOXP2 activity. Many target genes are known to play critical roles in specific aspects of central nervous system patterning or development, such as neurite outgrowth, as well as plasticity. Subsets of the FOXP2 transcriptional targets are either under positive selection in humans or differentially expressed between human and chimpanzee brain. This is the first ChIP-chip study to use human brain tissue, making the FOXP2-target genes identified in these studies important to understanding the pathways regulating speech and language in the developing human brain. These data provide the first insight into the functional network of genes directly regulated by FOXP2 in human brain and by evolutionary comparisons, highlighting genes likely to be involved in the development of human higher-order cognitive processes. PMID:17999357

Development of a High Angular Resolution Diffusion Imaging Human Brain Template

PubMed Central

Varentsova, Anna; Zhang, Shengwei; Arfanakis, Konstantinos

2014-01-01

Brain diffusion templates contain rich information about the microstructure of the brain, and are used as references in spatial normalization or in the development of brain atlases. The accuracy of diffusion templates constructed based on the diffusion tensor (DT) model is limited in regions with complex neuronal micro-architecture. High angular resolution diffusion imaging (HARDI) overcomes limitations of the DT model and is capable of resolving intravoxel heterogeneity. However, when HARDI is combined with multiple-shot sequences to minimize image artifacts, the scan time becomes inappropriate for human brain imaging. In this work, an artifact-free HARDI template of the human brain was developed from low angular resolution multiple-shot diffusion data. The resulting HARDI template was produced in ICBM-152 space based on Turboprop diffusion data, was shown to resolve complex neuronal micro-architecture in regions with intravoxel heterogeneity, and contained fiber orientation information consistent with known human brain anatomy. PMID:24440528

Prediction of human errors by maladaptive changes in event-related brain networks.

PubMed

Eichele, Tom; Debener, Stefan; Calhoun, Vince D; Specht, Karsten; Engel, Andreas K; Hugdahl, Kenneth; von Cramon, D Yves; Ullsperger, Markus

2008-04-22

Humans engaged in monotonous tasks are susceptible to occasional errors that may lead to serious consequences, but little is known about brain activity patterns preceding errors. Using functional MRI and applying independent component analysis followed by deconvolution of hemodynamic responses, we studied error preceding brain activity on a trial-by-trial basis. We found a set of brain regions in which the temporal evolution of activation predicted performance errors. These maladaptive brain activity changes started to evolve approximately 30 sec before the error. In particular, a coincident decrease of deactivation in default mode regions of the brain, together with a decline of activation in regions associated with maintaining task effort, raised the probability of future errors. Our findings provide insights into the brain network dynamics preceding human performance errors and suggest that monitoring of the identified precursor states may help in avoiding human errors in critical real-world situations.

Prediction of human errors by maladaptive changes in event-related brain networks

PubMed Central

Eichele, Tom; Debener, Stefan; Calhoun, Vince D.; Specht, Karsten; Engel, Andreas K.; Hugdahl, Kenneth; von Cramon, D. Yves; Ullsperger, Markus

2008-01-01

Humans engaged in monotonous tasks are susceptible to occasional errors that may lead to serious consequences, but little is known about brain activity patterns preceding errors. Using functional MRI and applying independent component analysis followed by deconvolution of hemodynamic responses, we studied error preceding brain activity on a trial-by-trial basis. We found a set of brain regions in which the temporal evolution of activation predicted performance errors. These maladaptive brain activity changes started to evolve ≈30 sec before the error. In particular, a coincident decrease of deactivation in default mode regions of the brain, together with a decline of activation in regions associated with maintaining task effort, raised the probability of future errors. Our findings provide insights into the brain network dynamics preceding human performance errors and suggest that monitoring of the identified precursor states may help in avoiding human errors in critical real-world situations. PMID:18427123

Listeriolysin O mediates cytotoxicity against human brain microvascular

USDA-ARS?s Scientific Manuscript database

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

A New Antigen Retrieval Technique for Human Brain Tissue

PubMed Central

Byne, William; Haroutunian, Vahram; García-Villanueva, Mercedes; Rábano, Alberto; García-Amado, María; Prensa, Lucía; Giménez-Amaya, José Manuel

2008-01-01

Immunohistochemical staining of tissues is a powerful tool used to delineate the presence or absence of an antigen. During the last 30 years, antigen visualization in human brain tissue has been significantly limited by the masking effect of fixatives. In the present study, we have used a new method for antigen retrieval in formalin-fixed human brain tissue and examined the effectiveness of this protocol to reveal masked antigens in tissues with both short and long formalin fixation times. This new method, which is based on the use of citraconic acid, has not been previously utilized in brain tissue although it has been employed in various other tissues such as tonsil, ovary, skin, lymph node, stomach, breast, colon, lung and thymus. Thus, we reported here a novel method to carry out immunohistochemical studies in free-floating human brain sections. Since fixation of brain tissue specimens in formaldehyde is a commonly method used in brain banks, this new antigen retrieval method could facilitate immunohistochemical studies of brains with prolonged formalin fixation times. PMID:18852880

Hollow Polypropylene Yarns as a Biomimetic Brain Phantom for the Validation of High-Definition Fiber Tractography Imaging.

PubMed

Guise, Catarina; Fernandes, Margarida M; Nóbrega, João M; Pathak, Sudhir; Schneider, Walter; Fangueiro, Raul

2016-11-09

Current brain imaging methods largely fail to provide detailed information about the location and severity of axonal injuries and do not anticipate recovery of the patients with traumatic brain injury. High-definition fiber tractography appears as a novel imaging modality based on water motion in the brain that allows for direct visualization and quantification of the degree of axons damage, thus predicting the functional deficits due to traumatic axonal injury and loss of cortical projections. This neuroimaging modality still faces major challenges because it lacks a "gold standard" for the technique validation and respective quality control. The present work aims to study the potential of hollow polypropylene yarns to mimic human white matter axons and construct a brain phantom for the calibration and validation of brain diffusion techniques based on magnetic resonance imaging, including high-definition fiber tractography imaging. Hollow multifilament polypropylene yarns were produced by melt-spinning process and characterized in terms of their physicochemical properties. Scanning electronic microscopy images of the filaments cross section has shown an inner diameter of approximately 12 μm, confirming their appropriateness to mimic the brain axons. The chemical purity of polypropylene yarns as well as the interaction between the water and the filament surface, important properties for predicting water behavior and diffusion inside the yarns, were also evaluated. Restricted and hindered water diffusion was confirmed by fluorescence microscopy. Finally, the yarns were magnetic resonance imaging scanned and analyzed using high-definition fiber tractography, revealing an excellent choice of these hollow polypropylene structures for simulation of the white matter brain axons and their suitability for constructing an accurate brain phantom.

Noninvasive quantification of human brain antioxidant concentrations after an intravenous bolus of vitamin C

USDA-ARS?s Scientific Manuscript database

Background: Until now, antioxidant based initiatives for preventing dementia have lacked a means to detect deficiency or measure pharmacologic effect in the human brain in situ. Objective: Our objective was to apply a novel method to measure key human brain antioxidant concentrations throughout the ...

Relationship between concentrations of lutein and StARD3 among pediatric and geriatric human brain tissue

USDA-ARS?s Scientific Manuscript database

Lutein, a dietary carotenoid, selectively accumulates in human retina and brain. While many epidemiological studies show evidence of a relationship between lutein status and cognitive health, lutein's selective uptake in human brain tissue and its potential function in early neural development and c...

Immunohistochemical Demonstration of Specific Antigens in the Human Brain Fixed in Zinc-ethanol-Formaldehyde

PubMed Central

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

2015-01-01

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

Convergent transcriptional specializations in the brains of humans and song-learning birds

PubMed Central

Pfenning, Andreas R.; Hara, Erina; Whitney, Osceola; Rivas, Miriam V.; Wang, Rui; Roulhac, Petra L.; Howard, Jason T.; Wirthlin, Morgan; Lovell, Peter V.; Ganapathy, Ganeshkumar; Mouncastle, Jacquelyn; Moseley, M. Arthur; Thompson, J. Will; Soderblom, Erik J.; Iriki, Atsushi; Kato, Masaki; Gilbert, M. Thomas P.; Zhang, Guojie; Bakken, Trygve; Bongaarts, Angie; Bernard, Amy; Lein, Ed; Mello, Claudio V.; Hartemink, Alexander J.; Jarvis, Erich D.

2015-01-01

Song-learning birds and humans share independently evolved similarities in brain pathways for vocal learning that are essential for song and speech and are not found in most other species. Comparisons of brain transcriptomes of song-learning birds and humans relative to vocal nonlearners identified convergent gene expression specializations in specific song and speech brain regions of avian vocal learners and humans. The strongest shared profiles relate bird motor and striatal song-learning nuclei, respectively, with human laryngeal motor cortex and parts of the striatum that control speech production and learning. Most of the associated genes function in motor control and brain connectivity. Thus, convergent behavior and neural connectivity for a complex trait are associated with convergent specialized expression of multiple genes. PMID:25504733

A simple physiologically based pharmacokinetic model evaluating the effect of anti-nicotine antibodies on nicotine disposition in the brains of rats and humans

PubMed Central

Saylor, Kyle; Zhang, Chenming

2017-01-01

Physiologically based pharmacokinetic (PBPK) modeling was applied to investigate the effects of anti-nicotine antibodies on nicotine disposition in the brains of rats and humans. Successful construction of both rat and human models was achieved by fitting model outputs to published nicotine concentration time course data in the blood and in the brain. Key parameters presumed to have the most effect on the ability of these antibodies to prevent nicotine from entering the brain were selected for investigation using the human model. These parameters, which included antibody affinity for nicotine, antibody cross-reactivity with cotinine, and antibody concentration, were broken down into different, clinically-derived in silico treatment levels and fed into the human PBPK model. Model predictions suggested that all three parameters, in addition to smoking status, have a sizable impact on anti-nicotine antibodies’ ability to prevent nicotine from entering the brain and that the antibodies elicited by current human vaccines do not have sufficient binding characteristics to reduce brain nicotine concentrations. If the antibody binding characteristics achieved in animal studies can similarly be achieved in human studies, however, nicotine vaccine efficacy in terms of brain nicotine concentration reduction is predicted to meet threshold values for alleviating nicotine dependence. PMID:27473014

Beyond sex differences: new approaches for thinking about variation in brain structure and function.

PubMed

Joel, Daphna; Fausto-Sterling, Anne

2016-02-19

In the study of variation in brain structure and function that might relate to sex and gender, language matters because it frames our research questions and methods. In this article, we offer an approach to thinking about variation in brain structure and function that pulls us outside the sex differences formulation. We argue that the existence of differences between the brains of males and females does not unravel the relations between sex and the brain nor is it sufficient to characterize a population of brains. Such characterization is necessary for studying sex effects on the brain as well as for studying brain structure and function in general. Animal studies show that sex interacts with environmental, developmental and genetic factors to affect the brain. Studies of humans further suggest that human brains are better described as belonging to a single heterogeneous population rather than two distinct populations. We discuss the implications of these observations for studies of brain and behaviour in humans and in laboratory animals. We believe that studying sex effects in context and developing or adopting analytical methods that take into account the heterogeneity of the brain are crucial for the advancement of human health and well-being. © 2016 The Author(s).

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. Copyright © 2015 Elsevier Ltd. All rights reserved.

Studying frequency processing of the brain to enhance long-term memory and develop a human brain protocol.

PubMed

Friedrich, Wernher; Du, Shengzhi; Balt, Karlien

2015-01-01

The temporal lobe in conjunction with the hippocampus is responsible for memory processing. The gamma wave is involved with this process. To develop a human brain protocol, a better understanding of the relationship between gamma and long-term memory is vital. A more comprehensive understanding of the human brain and specific analogue waves it uses will support the development of a human brain protocol. Fifty-eight participants aged between 6 and 60 years participated in long-term memory experiments. It is envisaged that the brain could be stimulated through binaural beats (sound frequency) at 40 Hz (gamma) to enhance long-term memory capacity. EEG recordings have been transformed to sound and then to an information standard, namely ASCII. Statistical analysis showed a proportional relationship between long-term memory and gamma activity. Results from EEG recordings indicate a pattern. The pattern was obtained through the de-codification of an EEG recording to sound and then to ASCII. Stimulation of gamma should enhance long term memory capacity. More research is required to unlock the human brains' protocol key. This key will enable the processing of information directly to and from human memory via gamma, the hippocampus and the temporal lobe.

The neural response properties and cortical organization of a rapidly adapting muscle sensory group response that overlaps with the frequencies that elicit the kinesthetic illusion.

PubMed

Marasco, Paul D; Bourbeau, Dennis J; Shell, Courtney E; Granja-Vazquez, Rafael; Ina, Jason G

2017-01-01

Kinesthesia is the sense of limb movement. It is fundamental to efficient motor control, yet its neurophysiological components remain poorly understood. The contributions of primary muscle spindles and cutaneous afferents to the kinesthetic sense have been well studied; however, potential contributions from muscle sensory group responses that are different than the muscle spindles have not been ruled out. Electrophysiological recordings in peripheral nerves and brains of male Sprague Dawley rats with a degloved forelimb preparation provide evidence of a rapidly adapting muscle sensory group response that overlaps with vibratory inputs known to generate illusionary perceptions of limb movement in humans (kinesthetic illusion). This group was characteristically distinct from type Ia muscle spindle fibers, the receptor historically attributed to limb movement sensation, suggesting that type Ia muscle spindle fibers may not be the sole carrier of kinesthetic information. The sensory-neural structure of muscles is complex and there are a number of possible sources for this response group; with Golgi tendon organs being the most likely candidate. The rapidly adapting muscle sensory group response projected to proprioceptive brain regions, the rodent homolog of cortical area 3a and the second somatosensory area (S2), with similar adaption and frequency response profiles between the brain and peripheral nerves. Their representational organization was muscle-specific (myocentric) and magnified for proximal and multi-articulate limb joints. Projection to proprioceptive brain areas, myocentric representational magnification of muscles prone to movement error, overlap with illusionary vibrational input, and resonant frequencies of volitional motor unit contraction suggest that this group response may be involved with limb movement processing.

The neural response properties and cortical organization of a rapidly adapting muscle sensory group response that overlaps with the frequencies that elicit the kinesthetic illusion

PubMed Central

Marasco, Paul D.; Bourbeau, Dennis J.; Shell, Courtney E.; Granja-Vazquez, Rafael; Ina, Jason G.

2017-01-01

Kinesthesia is the sense of limb movement. It is fundamental to efficient motor control, yet its neurophysiological components remain poorly understood. The contributions of primary muscle spindles and cutaneous afferents to the kinesthetic sense have been well studied; however, potential contributions from muscle sensory group responses that are different than the muscle spindles have not been ruled out. Electrophysiological recordings in peripheral nerves and brains of male Sprague Dawley rats with a degloved forelimb preparation provide evidence of a rapidly adapting muscle sensory group response that overlaps with vibratory inputs known to generate illusionary perceptions of limb movement in humans (kinesthetic illusion). This group was characteristically distinct from type Ia muscle spindle fibers, the receptor historically attributed to limb movement sensation, suggesting that type Ia muscle spindle fibers may not be the sole carrier of kinesthetic information. The sensory-neural structure of muscles is complex and there are a number of possible sources for this response group; with Golgi tendon organs being the most likely candidate. The rapidly adapting muscle sensory group response projected to proprioceptive brain regions, the rodent homolog of cortical area 3a and the second somatosensory area (S2), with similar adaption and frequency response profiles between the brain and peripheral nerves. Their representational organization was muscle-specific (myocentric) and magnified for proximal and multi-articulate limb joints. Projection to proprioceptive brain areas, myocentric representational magnification of muscles prone to movement error, overlap with illusionary vibrational input, and resonant frequencies of volitional motor unit contraction suggest that this group response may be involved with limb movement processing. PMID:29182648

Human-specific features of spatial gene expression and regulation in eight brain regions.

PubMed

Xu, Chuan; Li, Qian; Efimova, Olga; He, Liu; Tatsumoto, Shoji; Stepanova, Vita; Oishi, Takao; Udono, Toshifumi; Yamaguchi, Katsushi; Shigenobu, Shuji; Kakita, Akiyoshi; Nawa, Hiroyuki; Khaitovich, Philipp; Go, Yasuhiro

2018-06-13

Molecular maps of the human brain alone do not inform us of the features unique to humans. Yet, the identification of these features is important for understanding both the evolution and nature of human cognition. Here, we approached this question by analyzing gene expression and H3K27ac chromatin modification data collected in eight brain regions of humans, chimpanzees, gorillas, a gibbon and macaques. An analysis of spatial transcriptome trajectories across eight brain regions in four primate species revealed 1,851 genes showing human-specific transcriptome differences in one or multiple brain regions, in contrast to 240 chimpanzee-specific ones. More than half of these human-specific differences represented elevated expression of genes enriched in neuronal and astrocytic markers in the human hippocampus, while the rest were enriched in microglial markers and displayed human-specific expression in several frontal cortical regions and the cerebellum. An analysis of the predicted regulatory interactions driving these differences revealed the role of transcription factors in species-specific transcriptome changes, while epigenetic modifications were linked to spatial expression differences conserved across species. Published by Cold Spring Harbor Laboratory Press.

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

PubMed

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

2017-01-04

The serotonin (5-hydroxytryptamine, 5-HT) system modulates many important brain functions and is critically involved in many neuropsychiatric disorders. Here, we present a high-resolution, multidimensional, in vivo atlas of four of the human brain's 5-HT receptors (5-HT 1A , 5-HT 1B , 5-HT 2A , and 5-HT 4 ) and the 5-HT transporter (5-HTT). The atlas is created from molecular and structural high-resolution neuroimaging data consisting of positron emission tomography (PET) and magnetic resonance imaging (MRI) scans acquired in a total of 210 healthy individuals. Comparison of the regional PET binding measures with postmortem human brain autoradiography outcomes showed a high correlation for the five 5-HT targets and this enabled us to transform the atlas to represent protein densities (in picomoles per milliliter). We also assessed the regional association between protein concentration and mRNA expression in the human brain by comparing the 5-HT density across the atlas with data from the Allen Human Brain atlas and identified receptor- and transporter-specific associations that show the regional relation between the two measures. Together, these data provide unparalleled insight into the serotonin system of the human brain. We present a high-resolution positron emission tomography (PET)- and magnetic resonance imaging-based human brain atlas of important serotonin receptors and the transporter. The regional PET-derived binding measures correlate strongly with the corresponding autoradiography protein levels. The strong correlation enables the transformation of the PET-derived human brain atlas into a protein density map of the serotonin (5-hydroxytryptamine, 5-HT) system. Next, we compared the regional receptor/transporter protein densities with mRNA levels and uncovered unique associations between protein expression and density at high detail. This new in vivo neuroimaging atlas of the 5-HT system not only provides insight in the human brain's regional protein synthesis, transport, and density, but also represents a valuable source of information for the neuroscience community as a comparative instrument to assess brain disorders. Copyright © 2017 the authors 0270-6474/17/370120-09$15.00/0.

Photoacoustic Imaging of Animals with an Annular Transducer Array

NASA Astrophysics Data System (ADS)

Yang, Di-Wu; Zhou, Zhi-Bin; Zeng, Lv-Ming; Zhou, Xin; Chen, Xing-Hui

2014-07-01

A photoacoustic system with an annular transducer array is presented for rapid, high-resolution photoacoustic tomography of animals. An eight-channel data acquisition system is applied to capture the photoacoustic signals by using multiplexing and the total time of data acquisition and transferring is within 3 s. A limited-view filtered back projection algorithm is used to reconstruct the photoacoustic images. Experiments are performed on a mouse head and a rabbit head and clear photoacoustic images are obtained. The experimental results demonstrate that this imaging system holds the potential for imaging the human brain.

A role for human brain pericytes in neuroinflammation

PubMed Central

2014-01-01

Background Brain inflammation plays a key role in neurological disease. Although much research has been conducted investigating inflammatory events in animal models, potential differences in human brain versus rodent models makes it imperative that we also study these phenomena in human cells and tissue. Methods Primary human brain cell cultures were generated from biopsy tissue of patients undergoing surgery for drug-resistant epilepsy. Cells were treated with pro-inflammatory compounds IFNγ, TNFα, IL-1β, and LPS, and chemokines IP-10 and MCP-1 were measured by immunocytochemistry, western blot, and qRT-PCR. Microarray analysis was also performed on late passage cultures treated with vehicle or IFNγ and IL-1β. Results Early passage human brain cell cultures were a mixture of microglia, astrocytes, fibroblasts and pericytes. Later passage cultures contained proliferating fibroblasts and pericytes only. Under basal culture conditions all cell types showed cytoplasmic NFκB indicating that they were in a non-activated state. Expression of IP-10 and MCP-1 were significantly increased in response to pro-inflammatory stimuli. The two chemokines were expressed in mixed cultures as well as cultures of fibroblasts and pericytes only. The expression of IP-10 and MCP-1 were regulated at the mRNA and protein level, and both were secreted into cell culture media. NFκB nuclear translocation was also detected in response to pro-inflammatory cues (except IFNγ) in all cell types. Microarray analysis of brain pericytes also revealed widespread changes in gene expression in response to the combination of IFNγ and IL-1β treatment including interleukins, chemokines, cellular adhesion molecules and much more. Conclusions Adult human brain cells are sensitive to cytokine challenge. As expected ‘classical’ brain immune cells, such as microglia and astrocytes, responded to cytokine challenge but of even more interest, brain pericytes also responded to such challenge with a rich repertoire of gene expression. Immune activation of brain pericytes may play an important role in communicating inflammatory signals to and within the brain interior and may also be involved in blood brain barrier (BBB) disruption . Targeting brain pericytes, as well as microglia and astrocytes, may provide novel opportunities for reducing brain inflammation and maintaining BBB function and brain homeostasis in human brain disease. PMID:24920309

Viral-genetic tracing of the input-output organization of a central noradrenaline circuit.

PubMed

Schwarz, Lindsay A; Miyamichi, Kazunari; Gao, Xiaojing J; Beier, Kevin T; Weissbourd, Brandon; DeLoach, Katherine E; Ren, Jing; Ibanes, Sandy; Malenka, Robert C; Kremer, Eric J; Luo, Liqun

2015-08-06

Deciphering how neural circuits are anatomically organized with regard to input and output is instrumental in understanding how the brain processes information. For example, locus coeruleus noradrenaline (also known as norepinephrine) (LC-NE) neurons receive input from and send output to broad regions of the brain and spinal cord, and regulate diverse functions including arousal, attention, mood and sensory gating. However, it is unclear how LC-NE neurons divide up their brain-wide projection patterns and whether different LC-NE neurons receive differential input. Here we developed a set of viral-genetic tools to quantitatively analyse the input-output relationship of neural circuits, and applied these tools to dissect the LC-NE circuit in mice. Rabies-virus-based input mapping indicated that LC-NE neurons receive convergent synaptic input from many regions previously identified as sending axons to the locus coeruleus, as well as from newly identified presynaptic partners, including cerebellar Purkinje cells. The 'tracing the relationship between input and output' method (or TRIO method) enables trans-synaptic input tracing from specific subsets of neurons based on their projection and cell type. We found that LC-NE neurons projecting to diverse output regions receive mostly similar input. Projection-based viral labelling revealed that LC-NE neurons projecting to one output region also project to all brain regions we examined. Thus, the LC-NE circuit overall integrates information from, and broadcasts to, many brain regions, consistent with its primary role in regulating brain states. At the same time, we uncovered several levels of specificity in certain LC-NE sub-circuits. These tools for mapping output architecture and input-output relationship are applicable to other neuronal circuits and organisms. More broadly, our viral-genetic approaches provide an efficient intersectional means to target neuronal populations based on cell type and projection pattern.

A case for human systems neuroscience.

PubMed

Gardner, J L

2015-06-18

Can the human brain itself serve as a model for a systems neuroscience approach to understanding the human brain? After all, how the brain is able to create the richness and complexity of human behavior is still largely mysterious. What better choice to study that complexity than to study it in humans? However, measurements of brain activity typically need to be made non-invasively which puts severe constraints on what can be learned about the internal workings of the brain. Our approach has been to use a combination of psychophysics in which we can use human behavioral flexibility to make quantitative measurements of behavior and link those through computational models to measurements of cortical activity through magnetic resonance imaging. In particular, we have tested various computational hypotheses about what neural mechanisms could account for behavioral enhancement with spatial attention (Pestilli et al., 2011). Resting both on quantitative measurements and considerations of what is known through animal models, we concluded that weighting of sensory signals by the magnitude of their response is a neural mechanism for efficient selection of sensory signals and consequent improvements in behavioral performance with attention. While animal models have many technical advantages over studying the brain in humans, we believe that human systems neuroscience should endeavor to validate, replicate and extend basic knowledge learned from animal model systems and thus form a bridge to understanding how the brain creates the complex and rich cognitive capacities of humans. Copyright © 2014 IBRO. Published by Elsevier Ltd. All rights reserved.

Treatment and prognosis of breast cancer patients with brain metastases according to intrinsic subtype.

PubMed

Kuba, Sayaka; Ishida, Mayumi; Nakamura, Yoshiaki; Yamanouchi, Kosho; Minami, Shigeki; Taguchi, Kenichi; Eguchi, Susumu; Ohno, Shinji

2014-11-01

How breast cancer subtypes should affect treatment decisions for breast cancer patients with brain metastases is unclear. We analyzed local brain metastases treatments and their outcomes according to subtype in patients with breast cancer and brain metastases. We reviewed records and database information for women treated at the National Kyushu Cancer Center between 2001 and 2010. Patients were divided into three breast cancer subtype groups: Luminal (estrogen receptor positive and/or progesterone receptor positive, but human epidermal growth factor receptor 2 negative); human epidermal growth factor receptor 2 positive and triple negative (estrogen receptor negative, progesterone receptor negative and human epidermal growth factor receptor 2 negative). Of 524 advanced breast cancer patients, we reviewed 65 (12%) with brain metastases and records showing estrogen receptor, progesterone receptor and human epidermal growth factor receptor 2 status, as well as outcome data; there were 26 (40%) Luminal, 26 (40%) had human epidermal growth factor receptor 2 and 13 (20%) had triple negative subtypes. There was no statistical difference in the number of brain metastases among subtypes; however, rates of stereotactic radiosurgery or surgery for brain metastases differed significantly by subtype (human epidermal growth factor receptor 2: 81%, Luminal: 42% and triple negative: 47%; P = 0.03). Patients having the human epidermal growth factor receptor 2 subtype, a performance status of ≤1 and ≤4 brain metastases, who underwent systemic therapy after brain metastases and underwent stereotactic radiosurgery or surgery, were predicted to have longer overall survival after brain metastases. Multivariate analysis demonstrated that not having systemic therapy and not having the human epidermal growth factor receptor 2 subtype were independent factors associated with an increased risk of death (hazard ratio 2.4, 95% confidence interval 1.01-5.6; P = 0.05 and hazard ratio 2.9, 95% confidence interval 1.5-5.8; P = 0.003, respectively). Our study showed that local brain treatments and prognosis differed by subtype in breast cancer patients with brain metastases. © The Author 2014. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

Carbohydrates as a cerebral metabolic fuel.

PubMed

Evans, M; Amiel, S A

1998-03-01

The human brain is an extremely active metabolic organ with little endogenous stores of energy. It is thus dependent on circulating glucose to fuel metabolism and support cognitive functioning. However there is growing evidence that the human brain is able to utilise other non-glucose fuels during times of glucose lack. We review the evidence for the potential of the human brain to use the alternate fuels lactate and beta-hydroxybutyrate, and some recent studies examining the ability of regions of brain to use non-glucose lipid fuels. The human brain does not seem to have the ability to use the gluconeogenic precursor alanine to any significant degree. Regionality within the brain can be examined in vivo by the use of positron emission tomography, which offers the exciting prospect of studying human brain metabolism in vivo using a simple and non-interventional technique. Increased understanding of the brain's metabolism, the way in which hypoglycaemia is recognised and the manner in which this can be altered in the syndrome of hypoglycaemia unawareness and deficient counterregulation will help develop further strategies to prevent the clinical problems associated with hypoglycaemia in insulin-dependent diabetic adults and children.

ABC transporters and cytochromes P450 in the human central nervous system: influence on brain pharmacokinetics and contribution to neurodegenerative disorders.

PubMed

Dutheil, Fabien; Jacob, Aude; Dauchy, Sandrine; Beaune, Philippe; Scherrmann, Jean-Michel; Declèves, Xavier; Loriot, Marie-Anne

2010-10-01

The identification of xenobiotic metabolizing enzymes (i.e., CYP) and transporters (i.e., ABC transporters) (XMET) in the human brain, including the BBB, raises the question whether these transporters and enzymes have specific functions in brain physiology, neuropharmacology and toxicology. Relevant literature was identified using PubMed search articles published up to March 2010. Search terms included 'ABC transporters and P450 or CYP', 'drug metabolism, effect and toxicity' and 'neurodegenerative disease (Alzheimer and Parkinson diseases)' restricted to the field of 'brain or human brain'. This review aims to provide a better understanding of XMET functions in the human brain and show their pharmacological importance for improving drug delivery and efficacy and also for managing their side effects. Finally, the impact of brain XMET activity during neurodegenerative processes is discussed, giving an opportunity to identify new markers of human brain diseases. During the last 2 decades, much evidence concerning the specific distribution patterns of XMET, their induction by xenobiotics and endobiotics and their genetic variations have made cerebral ABC transporters and CYP enzymes key elements in the way individual patients respond to centrally acting drugs.

[Is abortion murder?].

PubMed

Werning, C

1995-09-01

Discussions about Paragraph 218 of the German federal abortion law have spawned antithetical opinions: on the one hand, the full right of the mother or parents to decide about the incipient human life; and on the other hand, under the dogma of abortion is murder, providing abortion is rejected even when the pregnancy is the result of rape and it is unwanted. Two questions are closely related to this issue: 1) what makes human beings human and 2) when does human life begin. From a medical point of view the function of the brain is fundamentally linked to being human. The brain controls almost all functions of the body and determines its psychological makeup, such as intellect and, in a theological sense, the soul. Without the brain such functioning is not possible, since brain death means the death of human life. Children born with anencephaly and microencephaly can never live a human life. At the end of life various diseases (stroke, Alzheimer disease) can severely damage the brain. In these cases normal living is also no longer possible. Yet ethically it is untenable to actively kill these human beings. But when one considers that life-threatening diseases can require life-support intervention, then often the pragmatic intervention is not far removed from active euthanasia. The other question related to the beginning of human life is even more difficult to answer. It is the fertilization of the egg cells; but a conglomeration of cells in the early phase of pregnancy can hardly be characterized as a human person. The human identity, personality, and worth is associated with the functioning of the brain, so only when the brain is fully developed can there be any talk about an unborn human being.

Evidence of native α-synuclein conformers in the human brain.

PubMed

Gould, Neal; Mor, Danielle E; Lightfoot, Richard; Malkus, Kristen; Giasson, Benoit; Ischiropoulos, Harry

2014-03-14

α-Synuclein aggregation is central to the pathogenesis of several brain disorders. However, the native conformations and functions of this protein in the human brain are not precisely known. The native state of α-synuclein was probed by gel filtration coupled with native gradient gel separation, an array of antibodies with non-overlapping epitopes, and mass spectrometry. The existence of metastable conformers and stable monomer was revealed in the human brain.

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

PubMed

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

2018-01-01

Magnetic resonance elastography holds promise as a non-invasive, easy-to-use, in vivo biomarker for neurodegenerative diseases. Throughout the past decade, pigs have gained increased popularity as large animal models for human neurodegeneration. However, the volume of a pig brain is an order of magnitude smaller than the human brain, its skull is 40% thicker, and its head is about twice as big. This raises the question to which extent established vibration devices, actuation frequencies, and analysis tools for humans translate to large animal studies in pigs. Here we explored the feasibility of using human brain magnetic resonance elastography to characterize the dynamic properties of the porcine brain. In contrast to humans, where vibration devices induce an anterior-posterior displacement recorded in transverse sections, the porcine anatomy requires a dorsal-ventral displacement recorded in coronal sections. Within these settings, we applied a wide range of actuation frequencies, from 40Hz to 90Hz, and recorded the storage and loss moduli for human and porcine brains. Strikingly, we found that optimal actuation frequencies for humans translate one-to-one to pigs and reliably generate shear waves for elastographic post-processing. In a direct comparison, human and porcine storage and loss moduli followed similar trends and increased with increasing frequency. When translating these frequency-dependent storage and loss moduli into the frequency-independent stiffnesses and viscosities of a standard linear solid model, we found human values of μ 1 =1.3kPa, μ 2 =2.1kPa, and η=0.025kPas and porcine values of μ 1 =2.0kPa, μ 2 =4.9kPa, and η=0.046kPas. These results suggest that living human brain is softer and less viscous than dead porcine brain. Our study compares, for the first time, magnetic resonance elastography in human and porcine brains, and paves the way towards systematic interspecies comparison studies and ex vivo validation of magnetic resonance elastography as a whole. Copyright © 2017 Elsevier Ltd. All rights reserved.

Responses of brain and non-brain endothelial cells to meningitis-causing Escherichia coli K1.

PubMed

Paul-Satyaseela, Maneesh; Xie, Yi; Di Cello, Francescopaolo; Kim, Kwang Sik

2006-03-31

Bacterial interaction with specific host tissue may contribute to its propensity to cause an infection in a particular site. In this study, we examined whether meningitis-causing Escherichia coli K1 interaction with human brain microvascular endothelial cells, which constitute the blood-brain barrier, differed from its interaction with non-brain endothelial cells derived from skin and umbilical cord. We showed that E. coli K1 association was significantly greater with human brain microvascular endothelial cells than with non-brain endothelial cells. In addition, human brain microvascular endothelial cells maintained their morphology and intercellular junctional resistance in response to E. coli K1. In contrast, non-brain endothelial cells exhibited decreased transendothelial electrical resistance and detachment from the matrix upon exposure to E. coli K1. These different responses of brain and non-brain endothelial cells to E. coli K1 may form the basis of E. coli K1's propensity to cause meningitis.

78 FR 27036 - Final Priority. National Institute on Disability and Rehabilitation Research-Traumatic Brain...

Federal Register 2010, 2011, 2012, 2013, 2014

2013-05-09

... individuals with disabilities in conducting TBIMS research. Types of Priorities When inviting applications for... Rehabilitation Research--Traumatic Brain Injury Model Systems Centers Collaborative Research Project AGENCY... Services announces a priority for the Disability and Rehabilitation Research Projects and Centers Program...

At least eighty percent of brain grey matter is modifiable by physical activity: A review study.

PubMed

Batouli, Seyed Amir Hossein; Saba, Valiallah

2017-08-14

The human brain is plastic, i.e. it can show structural changes in response to the altered environment. Physical activity (PA) is a lifestyle factor which has significant associations with the structural and functional aspects of the human brain, as well as with the mind and body health. Many studies have reported regional/global brain volume increments due to exercising; however, a map which shows the overall extent of the influences of PAs on brain structure is not available. In this study, we collected all the reports on brain structural alterations in association with PA in healthy humans, and next, a brain map of the extent of these effects is provided. The results of this study showed that a large network of brain areas, equal to 82% of the total grey matter volume, were associated with PA. This finding has important implications in utilizing PA as a mediator factor for educational purposes in children, rehabilitation applications in patients, improving the cognitive abilities of the human brain such as in learning or memory, and preventing age-related brain deteriorations. Copyright © 2017 Elsevier B.V. All rights reserved.

Human primary mixed brain cultures: preparation, differentiation, characterization and application to neuroscience research.

PubMed

Ray, Balmiki; Chopra, Nipun; Long, Justin M; Lahiri, Debomoy K

2014-09-16

Culturing primary cortical neurons is an essential neuroscience technique. However, most cultures are derived from rodent brains and standard protocols for human brain cultures are sparse. Herein, we describe preparation, maintenance and major characteristics of a primary human mixed brain culture, including neurons, obtained from legally aborted fetal brain tissue. This approach employs standard materials and techniques used in the preparation of rodent neuron cultures, with critical modifications. This culture has distinct differences from rodent cultures. Specifically, a significant numbers of cells in the human culture are derived from progenitor cells, and the yield and survival of the cells grossly depend on the presence of bFGF. In the presence of bFGF, this culture can be maintained for an extended period. Abundant productions of amyloid-β, tau and proteins make this a powerful model for Alzheimer's research. The culture also produces glia and different sub-types of neurons. We provide a well-characterized methodology for human mixed brain cultures useful to test therapeutic agents under various conditions, and to carry forward mechanistic and translational studies for several brain disorders.

A Hybrid CPU-GPU Accelerated Framework for Fast Mapping of High-Resolution Human Brain Connectome

PubMed Central

Ren, Ling; Xu, Mo; Xie, Teng; Gong, Gaolang; Xu, Ningyi; Yang, Huazhong; He, Yong

2013-01-01

Recently, a combination of non-invasive neuroimaging techniques and graph theoretical approaches has provided a unique opportunity for understanding the patterns of the structural and functional connectivity of the human brain (referred to as the human brain connectome). Currently, there is a very large amount of brain imaging data that have been collected, and there are very high requirements for the computational capabilities that are used in high-resolution connectome research. In this paper, we propose a hybrid CPU-GPU framework to accelerate the computation of the human brain connectome. We applied this framework to a publicly available resting-state functional MRI dataset from 197 participants. For each subject, we first computed Pearson’s Correlation coefficient between any pairs of the time series of gray-matter voxels, and then we constructed unweighted undirected brain networks with 58 k nodes and a sparsity range from 0.02% to 0.17%. Next, graphic properties of the functional brain networks were quantified, analyzed and compared with those of 15 corresponding random networks. With our proposed accelerating framework, the above process for each network cost 80∼150 minutes, depending on the network sparsity. Further analyses revealed that high-resolution functional brain networks have efficient small-world properties, significant modular structure, a power law degree distribution and highly connected nodes in the medial frontal and parietal cortical regions. These results are largely compatible with previous human brain network studies. Taken together, our proposed framework can substantially enhance the applicability and efficacy of high-resolution (voxel-based) brain network analysis, and have the potential to accelerate the mapping of the human brain connectome in normal and disease states. PMID:23675425

Hemispheric Specialization and the Growth of Human Understanding.

ERIC Educational Resources Information Center

Kinsbourne, Marcel

1982-01-01

Connectionistic notions of hemispheric specialization and use are incompatible with the network organization of the human brain. Although brain organization has correspondence with phenomena at more complex levels of analysis, the correspondence is not categorical in nature, as has been claimed by the left-brain/right-brain theorists. (Author/GC)

Sex beyond the genitalia: The human brain mosaic

PubMed Central

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

2015-01-01

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

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

PubMed

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

2014-01-01

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

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

PubMed Central

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

2014-01-01

Human sensory and motor systems provide the natural means for the exchange of information between individuals, and, hence, the basis for human civilization. The recent development of brain-computer interfaces (BCI) has provided an important element for the creation of brain-to-brain communication systems, and precise brain stimulation techniques are now available for the realization of non-invasive computer-brain interfaces (CBI). These technologies, BCI and CBI, can be combined to realize the vision of non-invasive, computer-mediated brain-to-brain (B2B) communication between subjects (hyperinteraction). Here we demonstrate the conscious transmission of information between human brains through the intact scalp and without intervention of motor or peripheral sensory systems. Pseudo-random binary streams encoding words were transmitted between the minds of emitter and receiver subjects separated by great distances, representing the realization of the first human brain-to-brain interface. In a series of experiments, we established internet-mediated B2B communication by combining a BCI based on voluntary motor imagery-controlled electroencephalographic (EEG) changes with a CBI inducing the conscious perception of phosphenes (light flashes) through neuronavigated, robotized transcranial magnetic stimulation (TMS), with special care taken to block sensory (tactile, visual or auditory) cues. Our results provide a critical proof-of-principle demonstration for the development of conscious B2B communication technologies. More fully developed, related implementations will open new research venues in cognitive, social and clinical neuroscience and the scientific study of consciousness. We envision that hyperinteraction technologies will eventually have a profound impact on the social structure of our civilization and raise important ethical issues. PMID:25137064

Human and animal cognition: Continuity and discontinuity

PubMed Central

Premack, David

2007-01-01

Microscopic study of the human brain has revealed neural structures, enhanced wiring, and forms of connectivity among nerve cells not found in any animal, challenging the view that the human brain is simply an enlarged chimpanzee brain. On the other hand, cognitive studies have found animals to have abilities once thought unique to the human. This suggests a disparity between brain and mind. The suggestion is misleading. Cognitive research has not kept pace with neural research. Neural findings are based on microscopic study of the brain and are primarily cellular. Because cognition cannot be studied microscopically, we need to refine the study of cognition by using a different approach. In examining claims of similarity between animals and humans, one must ask: What are the dissimilarities? This approach prevents confusing similarity with equivalence. We follow this approach in examining eight cognitive cases—teaching, short-term memory, causal reasoning, planning, deception, transitive inference, theory of mind, and language—and find, in all cases, that similarities between animal and human abilities are small, dissimilarities large. There is no disparity between brain and mind. PMID:17717081

Functional organization of the transcriptome in human brain

PubMed Central

Oldham, Michael C; Konopka, Genevieve; Iwamoto, Kazuya; Langfelder, Peter; Kato, Tadafumi; Horvath, Steve; Geschwind, Daniel H

2009-01-01

The enormous complexity of the human brain ultimately derives from a finite set of molecular instructions encoded in the human genome. These instructions can be directly studied by exploring the organization of the brain’s transcriptome through systematic analysis of gene coexpression relationships. We analyzed gene coexpression relationships in microarray data generated from specific human brain regions and identified modules of coexpressed genes that correspond to neurons, oligodendrocytes, astrocytes and microglia. These modules provide an initial description of the transcriptional programs that distinguish the major cell classes of the human brain and indicate that cell type–specific information can be obtained from whole brain tissue without isolating homogeneous populations of cells. Other modules corresponded to additional cell types, organelles, synaptic function, gender differences and the subventricular neurogenic niche. We found that subventricular zone astrocytes, which are thought to function as neural stem cells in adults, have a distinct gene expression pattern relative to protoplasmic astrocytes. Our findings provide a new foundation for neurogenetic inquiries by revealing a robust and previously unrecognized organization to the human brain transcriptome. PMID:18849986

Small-world human brain networks: Perspectives and challenges.

PubMed

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

2017-06-01

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

Dynamic Multi-Coil Shimming of the Human Brain at 7 Tesla

PubMed Central

Juchem, Christoph; Nixon, Terence W.; McIntyre, Scott; Boer, Vincent O.; Rothman, Douglas L.; de Graaf, Robin A.

2011-01-01

High quality magnetic field homogenization of the human brain (i.e. shimming) for MR imaging and spectroscopy is a demanding task. The susceptibility differences between air and tissue are a longstanding problem as they induce complex field distortions in the prefrontal cortex and the temporal lobes. To date, the theoretical gains of high field MR have only been realized partially in the human brain due to limited magnetic field homogeneity. A novel shimming technique for the human brain is presented that is based on the combination of non-orthogonal basis fields from 48 individual, circular coils. Custom-built amplifier electronics enabled the dynamic application of the multi-coil shim fields in a slice-specific fashion. Dynamic multi-coil (DMC) shimming is shown to eliminate most of the magnetic field inhomogeneity apparent in the human brain at 7 Tesla and provided improved performance compared to state-of-the-art dynamic shim updating with zero through third order spherical harmonic functions. The novel technique paves the way for high field MR applications of the human brain for which excellent magnetic field homogeneity is a prerequisite. PMID:21824794

Major involvement of Na(+) -dependent multivitamin transporter (SLC5A6/SMVT) in uptake of biotin and pantothenic acid by human brain capillary endothelial cells.

PubMed

Uchida, Yasuo; Ito, Katsuaki; Ohtsuki, Sumio; Kubo, Yoshiyuki; Suzuki, Takashi; Terasaki, Tetsuya

2015-07-01

The purpose of this study was to clarify the expression of Na(+) -dependent multivitamin transporter (SLC5A6/SMVT) and its contribution to the supply of biotin and pantothenic acid to the human brain via the blood-brain barrier. DNA microarray and immunohistochemical analyses confirmed that SLC5A6 is expressed in microvessels of human brain. The absolute expression levels of SLC5A6 protein in isolated human and monkey brain microvessels were 1.19 and 0.597 fmol/μg protein, respectively, as determined by a quantitative targeted absolute proteomics technique. Using an antibody-free method established by Kubo et al. (2015), we found that SLC5A6 was preferentially localized at the luminal membrane of brain capillary endothelium. Knock-down analysis using SLC5A6 siRNA showed that SLC5A6 accounts for 88.7% and 98.6% of total [(3) H]biotin and [(3) H]pantothenic acid uptakes, respectively, by human cerebral microvascular endothelial cell line hCMEC/D3. SLC5A6-mediated transport in hCMEC/D3 was markedly inhibited not only by biotin and pantothenic acid, but also by prostaglandin E2, lipoic acid, docosahexaenoic acid, indomethacin, ketoprofen, diclofenac, ibuprofen, phenylbutazone, and flurbiprofen. This study is the first to confirm expression of SLC5A6 in human brain microvessels and to provide evidence that SLC5A6 is a major contributor to luminal uptake of biotin and pantothenic acid at the human blood-brain barrier. In humans, it was unclear (not concluded) about what transport system at the blood-brain barrier (BBB) is responsible for the brain uptakes of two vitamins, biotin and pantothenic acid, which are necessary for brain proper function. This study clarified for the first time that the solute carrier 5A6/Na(+) -dependent multivitamin transporter SLC5A6/SMVT is responsible for the supplies of biotin and pantothenic acid into brain across the BBB in humans. DHA, docosahexaenoic acid; NSAID, non-steroidal anti-inflammatory drug; PGE2, prostaglandin E2. © 2015 International Society for Neurochemistry.

Relaxed genetic control of cortical organization in human brains compared with chimpanzees

PubMed Central

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

2015-01-01

The study of hominin brain evolution has focused largely on the neocortical expansion and reorganization undergone by humans as inferred from the endocranial fossil record. Comparisons of modern human brains with those of chimpanzees provide an additional line of evidence to define key neural traits that have emerged in human evolution and that underlie our unique behavioral specializations. In an attempt to identify fundamental developmental differences, we have estimated the genetic bases of brain size and cortical organization in chimpanzees and humans by studying phenotypic similarities between individuals with known kinship relationships. We show that, although heritability for brain size and cortical organization is high in chimpanzees, cerebral cortical anatomy is substantially less genetically heritable than brain size in humans, indicating greater plasticity and increased environmental influence on neurodevelopment in our species. This relaxed genetic control on cortical organization is especially marked in association areas and likely is related to underlying microstructural changes in neural circuitry. A major result of increased plasticity is that the development of neural circuits that underlie behavior is shaped by the environmental, social, and cultural context more intensively in humans than in other primate species, thus providing an anatomical basis for behavioral and cognitive evolution. PMID:26627234

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

PubMed

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

2017-06-08

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

Brain Imaging of Human Sexual Response: Recent Developments and Future Directions.

PubMed

Ruesink, Gerben B; Georgiadis, Janniko R

2017-01-01

The purpose of this study is to provide a comprehensive summary of the latest developments in the experimental brain study of human sexuality, focusing on brain connectivity during the sexual response. Stable patterns of brain activation have been established for different phases of the sexual response, especially with regard to the wanting phase, and changes in these patterns can be linked to sexual response variations, including sexual dysfunctions. From this solid basis, connectivity studies of the human sexual response have begun to add a deeper understanding of the brain network function and structure involved. The study of "sexual" brain connectivity is still very young. Yet, by approaching the brain as a connected organ, the essence of brain function is captured much more accurately, increasing the likelihood of finding useful biomarkers and targets for intervention in sexual dysfunction.

78 FR 13600 - Proposed Priority-National Institute on Disability and Rehabilitation Research-Traumatic Brain...

Federal Register 2010, 2011, 2012, 2013, 2014

2013-02-28

... designs. The research must focus on outcomes in one or more of the following domains identified in NIDRR's... Rehabilitation Research--Traumatic Brain Injury Model Systems Centers Collaborative Research Project [CFDA Number... Services proposes a priority under the Disability and Rehabilitation Research Projects and Centers Program...

Designing Schools Based on Brain Research.

ERIC Educational Resources Information Center

Chermayeff, Peter; Townsend, Ted

An audiotape explains an Iowa rainforest project that promotes experiential learning for children, and explores the effects of the physical environment on the brain. The project is a one-of-a-kind private/partnership that has created a fully integrated, seamless educational facility that combines a public school (prekindergarten through fifth…

T cells establish and maintain CNS viral infection in HIV-infected humanized mice.

PubMed

Honeycutt, Jenna B; Liao, Baolin; Nixon, Christopher C; Cleary, Rachel A; Thayer, William O; Birath, Shayla L; Swanson, Michael D; Sheridan, Patricia; Zakharova, Oksana; Prince, Francesca; Kuruc, JoAnn; Gay, Cynthia L; Evans, Chris; Eron, Joseph J; Wahl, Angela; Garcia, J Victor

2018-06-04

The human brain is an important site of HIV replication and persistence during antiretroviral therapy (ART). Direct evaluation of HIV infection in the brains of otherwise healthy individuals is not feasible; therefore, we performed a large-scale study of bone marrow/liver/thymus (BLT) humanized mice as an in vivo model to study HIV infection in the brain. Human immune cells, including CD4+ T cells and macrophages, were present throughout the BLT mouse brain. HIV DNA, HIV RNA, and/or p24+ cells were observed in the brains of HIV-infected animals, regardless of the HIV isolate used. HIV infection resulted in decreased numbers of CD4+ T cells, increased numbers of CD8+ T cells, and a decreased CD4+/CD8+ T cell ratio in the brain. Using humanized T cell-only mice (ToM), we demonstrated that T cells establish and maintain HIV infection of the brain in the complete absence of human myeloid cells. HIV infection of ToM resulted in CD4+ T cell depletion and a reduced CD4+/CD8+ T cell ratio. ART significantly reduced HIV levels in the BLT mouse brain, and the immune cell populations present were indistinguishable from those of uninfected controls, which demonstrated the effectiveness of ART in controlling HIV replication in the CNS and returning cellular homeostasis to a pre-HIV state.

Improved superficial brain hemorrhage visualization in susceptibility weighted images by constrained minimum intensity projection

NASA Astrophysics Data System (ADS)

Castro, Marcelo A.; Pham, Dzung L.; Butman, John

2016-03-01

Minimum intensity projection is a technique commonly used to display magnetic resonance susceptibility weighted images, allowing the observer to better visualize hemorrhages and vasculature. The technique displays the minimum intensity in a given projection within a thick slab, allowing different connectivity patterns to be easily revealed. Unfortunately, the low signal intensity of the skull within the thick slab can mask superficial tissues near the skull base and other regions. Because superficial microhemorrhages are a common feature of traumatic brain injury, this effect limits the ability to proper diagnose and follow up patients. In order to overcome this limitation, we developed a method to allow minimum intensity projection to properly display superficial tissues adjacent to the skull. Our approach is based on two brain masks, the largest of which includes extracerebral voxels. The analysis of the rind within both masks containing the actual brain boundary allows reclassification of those voxels initially missed in the smaller mask. Morphological operations are applied to guarantee accuracy and topological correctness, and the mean intensity within the mask is assigned to all outer voxels. This prevents bone from dominating superficial regions in the projection, enabling superior visualization of cortical hemorrhages and vessels.

Comparative Methylome Analyses Identify Epigenetic Regulatory Loci of Human Brain Evolution.

PubMed

Mendizabal, Isabel; Shi, Lei; Keller, Thomas E; Konopka, Genevieve; Preuss, Todd M; Hsieh, Tzung-Fu; Hu, Enzhi; Zhang, Zhe; Su, Bing; Yi, Soojin V

2016-11-01

How do epigenetic modifications change across species and how do these modifications affect evolution? These are fundamental questions at the forefront of our evolutionary epigenomic understanding. Our previous work investigated human and chimpanzee brain methylomes, but it was limited by the lack of outgroup data which is critical for comparative (epi)genomic studies. Here, we compared whole genome DNA methylation maps from brains of humans, chimpanzees and also rhesus macaques (outgroup) to elucidate DNA methylation changes during human brain evolution. Moreover, we validated that our approach is highly robust by further examining 38 human-specific DMRs using targeted deep genomic and bisulfite sequencing in an independent panel of 37 individuals from five primate species. Our unbiased genome-scan identified human brain differentially methylated regions (DMRs), irrespective of their associations with annotated genes. Remarkably, over half of the newly identified DMRs locate in intergenic regions or gene bodies. Nevertheless, their regulatory potential is on par with those of promoter DMRs. An intriguing observation is that DMRs are enriched in active chromatin loops, suggesting human-specific evolutionary remodeling at a higher-order chromatin structure. These findings indicate that there is substantial reprogramming of epigenomic landscapes during human brain evolution involving noncoding regions. © The Author 2016. Published by Oxford University Press on behalf of the Society for Molecular Biology and Evolution.

Dopaminergic Neurotransmission in the Human Brain: New Lessons from Perturbation and Imaging

PubMed Central

Ko, Ji Hyun; Strafella, Antonio P.

2012-01-01

Dopamine plays an important role in several brain functions and is involved in the pathogenesis of several psychiatric and neurological disorders. Neuroimaging techniques such as positron emission tomography allow us to quantify dopaminergic activity in the living human brain. Combining these with brain stimulation techniques offers us the unique opportunity to tackle questions regarding region-specific neurochemical activity. Such studies may aid clinicians and scientists to disentangle neural circuitries within the human brain and thereby help them to understand the underlying mechanisms of a given function in relation to brain diseases. Furthermore, it may also aid the development of alternative treatment approaches for various neurological and psychiatric conditions. PMID:21536838

Critical neuroscience—or critical science? A perspective on the perceived normative significance of neuroscience

PubMed Central

Schleim, Stephan

2014-01-01

Members of the Critical Neuroscience initiative raised the question whether the perceived normative significance of neuroscience is justified by the discipline’s actual possibilities. In this paper I show how brain research was assigned the ultimate political, social, and moral authority by some leading researchers who suggested that neuroscientists should change their research priorities, promising solutions to social challenges in order to increase research funds. Discussing the two examples of cognitive enhancement and the neuroscience of (im)moral behavior I argue that there is indeed a gap between promises and expectations on the one hand and knowledge and applications on the other. However it would be premature to generalize this to the neurosciences at large, whose knowledge-producing, innovative, and economic potentials have just recently been confirmed by political and scientific decision-makers with the financial support for the Human Brain Project and the BRAIN Initiative. Finally, I discuss two explanations for the analyzed communication patterns and argue why Critical Neuroscience is necessary, but not sufficient. A more general Critical Science movement is required to improve the scientific incentive system. PMID:24904376

Past and future corollaries of theories on causes of metabolic syndrome and obesity related co-morbidities part 2: a composite unifying theory review of human-specific co-adaptations to brain energy consumption.

PubMed

McGill, Anne-Thea

2014-01-01

Metabolic syndrome (MetS) predicts type II diabetes mellitus (TIIDM), cardiovascular disease (CVD) and cancer, and their rates have escalated over the last few decades. Obesity related co-morbidities also overlap the concept of the metabolic syndrome (MetS). However, understanding of the syndrome's underlying causes may have been misapprehended. The current paper follows on from a theory review by McGill, A-T in Archives of Public Health, 72: 30. This accompanying paper utilises research on human evolution and new biochemistry to theorise on why MetS and obesity arise and how they affect the population. The basis of this composite unifying theory is that the proportionately large, energy-demanding human brain may have driven co-adaptive mechanisms to provide, or conserve, energy for the brain. A 'dual system' is proposed. 1) The enlarged, complex cortico-limbic-striatal system increases dietary energy by developing strong neural self-reward/motivation pathways for the acquisition of energy dense food, and (2) the nuclear factor-erythroid 2-related factor 2 (NRF2) cellular protection system amplifies antioxidant, antitoxicant and repair activity by employing plant chemicals. In humans who consume a nutritious diet, the NRF2 system has become highly energy efficient. Other relevant human-specific co-adaptations are explored. In order to 'test' this composite unifying theory it is important to show that the hypothesis and sub-theories pertain throughout the whole of human evolution and history up till the current era. Corollaries of the composite unifying theory of MetS are examined with respect to past under-nutrition and malnutrition since agriculture began 10,000 years ago. The effects of man-made pollutants on degenerative change are examined. Projections are then made from current to future patterns on the state of 'insufficient micronutrient and/or unbalanced high energy malnutrition with central obesity and metabolic dysregulation' or 'malnubesity'. Forecasts on human health are made on positive, proactive strategies using the composite unifying theory, and are extended to the wider human ecology of food production. A comparison is made with the outlook for humans if current assumptions and the status quo on causes and treatments are maintained. Areas of further research are outlined. A table of suggestions for possible public health action is included.

Function-specific and Enhanced Brain Structural Connectivity Mapping via Joint Modeling of Diffusion and Functional MRI.

PubMed

Chu, Shu-Hsien; Parhi, Keshab K; Lenglet, Christophe

2018-03-16

A joint structural-functional brain network model is presented, which enables the discovery of function-specific brain circuits, and recovers structural connections that are under-estimated by diffusion MRI (dMRI). Incorporating information from functional MRI (fMRI) into diffusion MRI to estimate brain circuits is a challenging task. Usually, seed regions for tractography are selected from fMRI activation maps to extract the white matter pathways of interest. The proposed method jointly analyzes whole brain dMRI and fMRI data, allowing the estimation of complete function-specific structural networks instead of interactively investigating the connectivity of individual cortical/sub-cortical areas. Additionally, tractography techniques are prone to limitations, which can result in erroneous pathways. The proposed framework explicitly models the interactions between structural and functional connectivity measures thereby improving anatomical circuit estimation. Results on Human Connectome Project (HCP) data demonstrate the benefits of the approach by successfully identifying function-specific anatomical circuits, such as the language and resting-state networks. In contrast to correlation-based or independent component analysis (ICA) functional connectivity mapping, detailed anatomical connectivity patterns are revealed for each functional module. Results on a phantom (Fibercup) also indicate improvements in structural connectivity mapping by rejecting false-positive connections with insufficient support from fMRI, and enhancing under-estimated connectivity with strong functional correlation.

Lipid transport and human brain development.

PubMed

Betsholtz, Christer

2015-07-01

How the human brain rapidly builds up its lipid content during brain growth and maintains its lipids in adulthood has remained elusive. Two new studies show that inactivating mutations in MFSD2A, known to be expressed specifically at the blood-brain barrier, lead to microcephaly, thereby offering a simple and surprising solution to an old enigma.

Theoretical Implications of Contemporary Brain Science for Japanese EFL Learning

ERIC Educational Resources Information Center

Clayton, John Lloyd

2015-01-01

Recent advances in brain science show that adult native Japanese speakers utilize a different balance of language processing routes in the brain as compared to native English speakers. Biologically this represents the remarkable flexibility of the human brain to adapt universal human cognitive processes to fit the specific needs of linguistic and…

Aerobic glycolysis in the human brain is associated with development and neotenous gene expression

PubMed Central

Goyal, Manu S.; Hawrylycz, Michael; Miller, Jeremy A.; Snyder, Abraham Z.; Raichle, Marcus E.

2015-01-01

SUMMARY Aerobic glycolysis (AG), i.e., non-oxidative metabolism of glucose despite the presence of abundant oxygen, accounts for 10–12% of glucose used by the adult human brain. AG varies regionally in the resting state. Brain AG may support synaptic growth and remodeling; however, data supporting this hypothesis are sparse. Here, we report on investigations on the role of AG in the human brain. Meta-analysis of prior brain glucose and oxygen metabolism studies demonstrates that AG increases during childhood, precisely when synaptic growth rates are highest. In resting adult humans, AG correlates with persistence of gene expression typical of infancy (transcriptional neoteny). In brain regions with the highest AG, we find increased gene expression related to synapse formation and growth. In contrast, regions high in oxidative glucose metabolism express genes related to mitochondria and synaptic transmission. Our results suggest that brain AG supports developmental processes, particularly those required for synapse formation and growth. PMID:24411938

Cell lineage analysis in human brain using endogenous retroelements

PubMed Central

Evrony, Gilad D.; Lee, Eunjung; Mehta, Bhaven K.; Benjamini, Yuval; Johnson, Robert M.; Cai, Xuyu; Yang, Lixing; Haseley, Psalm; Lehmann, Hillel S.; Park, Peter J.; Walsh, Christopher A.

2015-01-01

Summary Somatic mutations occur during brain development and are increasingly implicated as a cause of neurogenetic disease. However, the patterns in which somatic mutations distribute in the human brain are unknown. We used high-coverage whole-genome sequencing of single neurons from a normal individual to identify spontaneous somatic mutations as clonal marks to track cell lineages in human brain. Somatic mutation analyses in >30 locations throughout the nervous system identified multiple lineages and sub-lineages of cells marked by different LINE-1 (L1) retrotransposition events and subsequent mutation of poly-A microsatellites within L1. One clone contained thousands of cells limited to the left middle frontal gyrus, whereas a second distinct clone contained millions of cells distributed over the entire left hemisphere. These patterns mirror known somatic mutation disorders of brain development, and suggest that focally distributed mutations are also prevalent in normal brains. Single-cell analysis of somatic mutation enables tracing of cell lineage clones in human brain. PMID:25569347

Development of a high angular resolution diffusion imaging human brain template.

PubMed

Varentsova, Anna; Zhang, Shengwei; Arfanakis, Konstantinos

2014-05-01

Brain diffusion templates contain rich information about the microstructure of the brain, and are used as references in spatial normalization or in the development of brain atlases. The accuracy of diffusion templates constructed based on the diffusion tensor (DT) model is limited in regions with complex neuronal micro-architecture. High angular resolution diffusion imaging (HARDI) overcomes limitations of the DT model and is capable of resolving intravoxel heterogeneity. However, when HARDI is combined with multiple-shot sequences to minimize image artifacts, the scan time becomes inappropriate for human brain imaging. In this work, an artifact-free HARDI template of the human brain was developed from low angular resolution multiple-shot diffusion data. The resulting HARDI template was produced in ICBM-152 space based on Turboprop diffusion data, was shown to resolve complex neuronal micro-architecture in regions with intravoxel heterogeneity, and contained fiber orientation information consistent with known human brain anatomy. Copyright © 2014 Elsevier Inc. All rights reserved.

A simple physiologically based pharmacokinetic model evaluating the effect of anti-nicotine antibodies on nicotine disposition in the brains of rats and humans

DOE Office of Scientific and Technical Information (OSTI.GOV)

Saylor, Kyle, E-mail: saylor@vt.edu; Zhang, Chenmi

Physiologically based pharmacokinetic (PBPK) modeling was applied to investigate the effects of anti-nicotine antibodies on nicotine disposition in the brains of rats and humans. Successful construction of both rat and human models was achieved by fitting model outputs to published nicotine concentration time course data in the blood and in the brain. Key parameters presumed to have the most effect on the ability of these antibodies to prevent nicotine from entering the brain were selected for investigation using the human model. These parameters, which included antibody affinity for nicotine, antibody cross-reactivity with cotinine, and antibody concentration, were broken down intomore » different, clinically-derived in silico treatment levels and fed into the human PBPK model. Model predictions suggested that all three parameters, in addition to smoking status, have a sizable impact on anti-nicotine antibodies' ability to prevent nicotine from entering the brain and that the antibodies elicited by current human vaccines do not have sufficient binding characteristics to reduce brain nicotine concentrations. If the antibody binding characteristics achieved in animal studies can similarly be achieved in human studies, however, nicotine vaccine efficacy in terms of brain nicotine concentration reduction is predicted to meet threshold values for alleviating nicotine dependence. - Highlights: • Modelling of nicotine disposition in the presence of anti-nicotine antibodies • Key vaccine efficacy factors are evaluated in silico in rats and in humans. • Model predicts insufficient antibody binding in past human nicotine vaccines. • Improving immunogenicity and antibody specificity may lead to vaccine success.« less

Connectivity profiles reveal the relationship between brain areas for social cognition in human and monkey temporoparietal cortex

PubMed Central

Mars, Rogier B.; Sallet, Jérôme; Neubert, Franz-Xaver; Rushworth, Matthew F. S.

2013-01-01

The human ability to infer the thoughts and beliefs of others, often referred to as “theory of mind,” as well as the predisposition to even consider others, are associated with activity in the temporoparietal junction (TPJ) area. Unlike the case of most human brain areas, we have little sense of whether or how TPJ is related to brain areas in other nonhuman primates. It is not possible to address this question by looking for similar task-related activations in nonhuman primates because there is no evidence that nonhuman primates engage in theory-of-mind tasks in the same manner as humans. Here, instead, we explore the relationship by searching for areas in the macaque brain that interact with other macaque brain regions in the same manner as human TPJ interacts with other human brain regions. In other words, we look for brain regions with similar positions within a distributed neural circuit in the two species. We exploited the fact that human TPJ has a unique functional connectivity profile with cortical areas with known homologs in the macaque. For each voxel in the macaque temporal and parietal cortex we evaluated the similarity of its functional connectivity profile to that of human TPJ. We found that areas in the middle part of the superior temporal cortex, often associated with the processing of faces and other social stimuli, have the most similar connectivity profile. These results suggest that macaque face processing areas and human mentalizing areas might have a similar precursor. PMID:23754406

Contribution of Neuroimaging Studies to Understanding Development of Human Cognitive Brain Functions

PubMed Central

Morita, Tomoyo; Asada, Minoru; Naito, Eiichi

2016-01-01

Humans experience significant physical and mental changes from birth to adulthood, and a variety of perceptual, cognitive and motor functions mature over the course of approximately 20 years following birth. To deeply understand such developmental processes, merely studying behavioral changes is not sufficient; simultaneous investigation of the development of the brain may lead us to a more comprehensive understanding. Recent advances in noninvasive neuroimaging technologies largely contribute to this understanding. Here, it is very important to consider the development of the brain from the perspectives of “structure” and “function” because both structure and function of the human brain mature slowly. In this review, we first discuss the process of structural brain development, i.e., how the structure of the brain, which is crucial when discussing functional brain development, changes with age. Second, we introduce some representative studies and the latest studies related to the functional development of the brain, particularly for visual, facial recognition, and social cognition functions, all of which are important for humans. Finally, we summarize how brain science can contribute to developmental study and discuss the challenges that neuroimaging should address in the future. PMID:27695409

Cell diversity and network dynamics in photosensitive human brain organoids

PubMed Central

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

2017-01-01

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

Cell diversity and network dynamics in photosensitive human brain organoids.

PubMed

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

2017-05-04

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

Developmental patterns of chimpanzee cerebral tissues provide important clues for understanding the remarkable enlargement of the human brain.

PubMed

Sakai, Tomoko; Matsui, Mie; Mikami, Akichika; Malkova, Ludise; Hamada, Yuzuru; Tomonaga, Masaki; Suzuki, Juri; Tanaka, Masayuki; Miyabe-Nishiwaki, Takako; Makishima, Haruyuki; Nakatsukasa, Masato; Matsuzawa, Tetsuro

2013-02-22

Developmental prolongation is thought to contribute to the remarkable brain enlargement observed in modern humans (Homo sapiens). However, the developmental trajectories of cerebral tissues have not been explored in chimpanzees (Pan troglodytes), even though they are our closest living relatives. To address this lack of information, the development of cerebral tissues was tracked in growing chimpanzees during infancy and the juvenile stage, using three-dimensional magnetic resonance imaging and compared with that of humans and rhesus macaques (Macaca mulatta). Overall, cerebral development in chimpanzees demonstrated less maturity and a more protracted course during prepuberty, as observed in humans but not in macaques. However, the rapid increase in cerebral total volume and proportional dynamic change in the cerebral tissue in humans during early infancy, when white matter volume increases dramatically, did not occur in chimpanzees. A dynamic reorganization of cerebral tissues of the brain during early infancy, driven mainly by enhancement of neuronal connectivity, is likely to have emerged in the human lineage after the split between humans and chimpanzees and to have promoted the increase in brain volume in humans. Our findings may lead to powerful insights into the ontogenetic mechanism underlying human brain enlargement.

Developmental patterns of chimpanzee cerebral tissues provide important clues for understanding the remarkable enlargement of the human brain

PubMed Central

Sakai, Tomoko; Matsui, Mie; Mikami, Akichika; Malkova, Ludise; Hamada, Yuzuru; Tomonaga, Masaki; Suzuki, Juri; Tanaka, Masayuki; Miyabe-Nishiwaki, Takako; Makishima, Haruyuki; Nakatsukasa, Masato; Matsuzawa, Tetsuro

2013-01-01

Developmental prolongation is thought to contribute to the remarkable brain enlargement observed in modern humans (Homo sapiens). However, the developmental trajectories of cerebral tissues have not been explored in chimpanzees (Pan troglodytes), even though they are our closest living relatives. To address this lack of information, the development of cerebral tissues was tracked in growing chimpanzees during infancy and the juvenile stage, using three-dimensional magnetic resonance imaging and compared with that of humans and rhesus macaques (Macaca mulatta). Overall, cerebral development in chimpanzees demonstrated less maturity and a more protracted course during prepuberty, as observed in humans but not in macaques. However, the rapid increase in cerebral total volume and proportional dynamic change in the cerebral tissue in humans during early infancy, when white matter volume increases dramatically, did not occur in chimpanzees. A dynamic reorganization of cerebral tissues of the brain during early infancy, driven mainly by enhancement of neuronal connectivity, is likely to have emerged in the human lineage after the split between humans and chimpanzees and to have promoted the increase in brain volume in humans. Our findings may lead to powerful insights into the ontogenetic mechanism underlying human brain enlargement. PMID:23256194

Metabolic acceleration and the evolution of human brain size and life history.

PubMed

Pontzer, Herman; Brown, Mary H; Raichlen, David A; Dunsworth, Holly; Hare, Brian; Walker, Kara; Luke, Amy; Dugas, Lara R; Durazo-Arvizu, Ramon; Schoeller, Dale; Plange-Rhule, Jacob; Bovet, Pascal; Forrester, Terrence E; Lambert, Estelle V; Thompson, Melissa Emery; Shumaker, Robert W; Ross, Stephen R

2016-05-19

Humans are distinguished from the other living apes in having larger brains and an unusual life history that combines high reproductive output with slow childhood growth and exceptional longevity. This suite of derived traits suggests major changes in energy expenditure and allocation in the human lineage, but direct measures of human and ape metabolism are needed to compare evolved energy strategies among hominoids. Here we used doubly labelled water measurements of total energy expenditure (TEE; kcal day(-1)) in humans, chimpanzees, bonobos, gorillas and orangutans to test the hypothesis that the human lineage has experienced an acceleration in metabolic rate, providing energy for larger brains and faster reproduction without sacrificing maintenance and longevity. In multivariate regressions including body size and physical activity, human TEE exceeded that of chimpanzees and bonobos, gorillas and orangutans by approximately 400, 635 and 820 kcal day(-1), respectively, readily accommodating the cost of humans' greater brain size and reproductive output. Much of the increase in TEE is attributable to humans' greater basal metabolic rate (kcal day(-1)), indicating increased organ metabolic activity. Humans also had the greatest body fat percentage. An increased metabolic rate, along with changes in energy allocation, was crucial in the evolution of human brain size and life history.

Sex differences in brain organization: implications for human communication.

PubMed

Hanske-Petitpierre, V; Chen, A C

1985-12-01

This article reviews current knowledge in two major research domains: sex differences in neuropsychophysiology, and in human communication. An attempt was made to integrate knowledge from several areas of brain research with human communication and to clarify how such a cooperative effort may be beneficial to both fields of study. By combining findings from the area of brain research, a communication paradigm was developed which contends that brain-related sex differences may reside largely in the area of communication of emotion.

Do glutathione levels decline in aging human brain?

PubMed

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

2016-04-01

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

Driving and driven architectures of directed small-world human brain functional networks.

PubMed

Yan, Chaogan; He, Yong

2011-01-01

Recently, increasing attention has been focused on the investigation of the human brain connectome that describes the patterns of structural and functional connectivity networks of the human brain. Many studies of the human connectome have demonstrated that the brain network follows a small-world topology with an intrinsically cohesive modular structure and includes several network hubs in the medial parietal regions. However, most of these studies have only focused on undirected connections between regions in which the directions of information flow are not taken into account. How the brain regions causally influence each other and how the directed network of human brain is topologically organized remain largely unknown. Here, we applied linear multivariate Granger causality analysis (GCA) and graph theoretical approaches to a resting-state functional MRI dataset with a large cohort of young healthy participants (n = 86) to explore connectivity patterns of the population-based whole-brain functional directed network. This directed brain network exhibited prominent small-world properties, which obviously improved previous results of functional MRI studies showing weak small-world properties in the directed brain networks in terms of a kernel-based GCA and individual analysis. This brain network also showed significant modular structures associated with 5 well known subsystems: fronto-parietal, visual, paralimbic/limbic, subcortical and primary systems. Importantly, we identified several driving hubs predominantly located in the components of the attentional network (e.g., the inferior frontal gyrus, supplementary motor area, insula and fusiform gyrus) and several driven hubs predominantly located in the components of the default mode network (e.g., the precuneus, posterior cingulate gyrus, medial prefrontal cortex and inferior parietal lobule). Further split-half analyses indicated that our results were highly reproducible between two independent subgroups. The current study demonstrated the directions of spontaneous information flow and causal influences in the directed brain networks, thus providing new insights into our understanding of human brain functional connectome.

A Thomistic defense of whole-brain death

PubMed Central

Eberl, Jason T.

2015-01-01

Michel Accad critiques the currently accepted whole-brain criterion for determining the death of a human being from a Thomistic metaphysical perspective and, in so doing, raises objections to a particular argument defending the whole-brain criterion by Patrick Lee and Germain Grisez. In this paper, I will respond to Accad's critique of the whole-brain criterion and defend its continued validity as a criterion for determining when a human being's death has occurred in accord with Thomistic metaphysical principles. I will, however, join Accad in criticizing Lee and Grisez's proposed defense of the whole-brain criterion as potentially leading to erroneous conclusions regarding the determination of human death. Lay summary: Catholic physicians and bioethicists currently debate the legally accepted clinical standard for determining when a human being has died—known as the “wholebrain criterion”—which has also been morally affirmed by the Magisterium. This paper responds to physician Michel Accad’s critique of the whole-brain criterion based upon St. Thomas Aquinas’s metaphysical account of human nature as a union of a rational soul and a material body. I defend the whole-brain criterion from the same Thomistic philosophical perspective, while agreeing with Accad’s objection to an alternative Thomistic defense of whole-brain death by philosophers Patrick Lee and Germain Grisez. PMID:26912933

A Thomistic defense of whole-brain death.

PubMed

Eberl, Jason T

2015-08-01

Michel Accad critiques the currently accepted whole-brain criterion for determining the death of a human being from a Thomistic metaphysical perspective and, in so doing, raises objections to a particular argument defending the whole-brain criterion by Patrick Lee and Germain Grisez. In this paper, I will respond to Accad's critique of the whole-brain criterion and defend its continued validity as a criterion for determining when a human being's death has occurred in accord with Thomistic metaphysical principles. I will, however, join Accad in criticizing Lee and Grisez's proposed defense of the whole-brain criterion as potentially leading to erroneous conclusions regarding the determination of human death. Lay summary: Catholic physicians and bioethicists currently debate the legally accepted clinical standard for determining when a human being has died-known as the "wholebrain criterion"-which has also been morally affirmed by the Magisterium. This paper responds to physician Michel Accad's critique of the whole-brain criterion based upon St. Thomas Aquinas's metaphysical account of human nature as a union of a rational soul and a material body. I defend the whole-brain criterion from the same Thomistic philosophical perspective, while agreeing with Accad's objection to an alternative Thomistic defense of whole-brain death by philosophers Patrick Lee and Germain Grisez.

Human immunodeficiency virus-infected macrophages produce soluble factors that cause histological and neurochemical alterations in cultured human brains.

PubMed Central

Pulliam, L; Herndier, B G; Tang, N M; McGrath, M S

1991-01-01

We wanted to establish an in vitro human model for AIDS-associated dementia and pursue the hypothesis that this disease process may be a result of soluble factors produced by HIV-infected macrophages. Human brain aggregates were prepared from nine different brain specimens, and were treated with supernatants from in vitro HIV-infected macrophages (SI), uninfected macrophages (SU), infected T cells, or macrophage-conditioned media from four AIDS patients. Seven of nine treated brains exposed to SI showed peripheral rarefaction after 1 wk of incubation that by ultrastructural analysis showed cytoplasmic vacuolation. Aggregates from two of three brain cultures treated with SI for 3 wk became smaller, an approximately 50% decrease in size. The degree of apparent toxicity in brains exposed to patient-derived macrophage supernatants paralleled the proportion of macrophages found to be expressing HIV p24. Ultrastructural abnormalities were not observed in brains treated with supernatants from HIV-infected T cells, uninfected macrophages, or LPS-activated macrophages. Levels of five neurotransmitter amino acids were decreased in comparison to the structural amino acid leucine. These findings suggest that HIV-infected macrophages, infected both in vitro as well as derived from AIDS patients' peripheral blood, produce factors that cause reproducible histochemical, ultrastructural, and functional abnormalities in human brain aggregates. Images PMID:1671392

The Search for True Numbers of Neurons and Glial Cells in the Human Brain: A Review of 150 Years of Cell Counting

PubMed Central

von Bartheld, Christopher S.; Bahney, Jami; Herculano-Houzel, Suzana

2016-01-01

For half a century, the human brain was believed to contain about 100 billion neurons and one trillion glial cells, with a glia:neuron ratio of 10:1. A new counting method, the isotropic fractionator, has challenged the notion that glia outnumber neurons and revived a question that was widely thought to have been resolved. The recently validated isotropic fractionator demonstrates a glia:neuron ratio of less than 1:1 and a total number of less than 100 billion glial cells in the human brain. A survey of original evidence shows that histological data always supported a 1:1 ratio of glia to neurons in the entire human brain, and a range of 40–130 billion glial cells. We review how the claim of one trillion glial cells originated, was perpetuated, and eventually refuted. We compile how numbers of neurons and glial cells in the adult human brain were reported and we examine the reasons for an erroneous consensus about the relative abundance of glial cells in human brains that persisted for half a century. Our review includes a brief history of cell counting in human brains, types of counting methods that were and are employed, ranges of previous estimates, and the current status of knowledge about the number of cells. We also discuss implications and consequences of the new insights into true numbers of glial cells in the human brain, and the promise and potential impact of the newly validated isotropic fractionator for reliable quantification of glia and neurons in neurological and psychiatric diseases. PMID:27187682

The search for true numbers of neurons and glial cells in the human brain: A review of 150 years of cell counting.

PubMed

von Bartheld, Christopher S; Bahney, Jami; Herculano-Houzel, Suzana

2016-12-15

For half a century, the human brain was believed to contain about 100 billion neurons and one trillion glial cells, with a glia:neuron ratio of 10:1. A new counting method, the isotropic fractionator, has challenged the notion that glia outnumber neurons and revived a question that was widely thought to have been resolved. The recently validated isotropic fractionator demonstrates a glia:neuron ratio of less than 1:1 and a total number of less than 100 billion glial cells in the human brain. A survey of original evidence shows that histological data always supported a 1:1 ratio of glia to neurons in the entire human brain, and a range of 40-130 billion glial cells. We review how the claim of one trillion glial cells originated, was perpetuated, and eventually refuted. We compile how numbers of neurons and glial cells in the adult human brain were reported and we examine the reasons for an erroneous consensus about the relative abundance of glial cells in human brains that persisted for half a century. Our review includes a brief history of cell counting in human brains, types of counting methods that were and are employed, ranges of previous estimates, and the current status of knowledge about the number of cells. We also discuss implications and consequences of the new insights into true numbers of glial cells in the human brain, and the promise and potential impact of the newly validated isotropic fractionator for reliable quantification of glia and neurons in neurological and psychiatric diseases. J. Comp. Neurol. 524:3865-3895, 2016. © 2016 Wiley Periodicals, Inc. © 2016 Wiley Periodicals, Inc.

Purification of a benzodiazepine from bovine brain and detection of benzodiazepine-like immunoreactivity in human brain.

PubMed Central

Sangameswaran, L; Fales, H M; Friedrich, P; De Blas, A L

1986-01-01

An endogenous brain substance that binds to the central-type benzodiazepine receptors with agonist properties is present in both rat and bovine brains. This substance has been purified to homogeneity from bovine brain by immunoaffinity chromatography on immobilized monoclonal anti-benzodiazepine antibody followed by gel filtration on Sephadex G-25 and two reversed-phase HPLC steps. The purified substance was characterized as the benzodiazepine N-desmethyldiazepam (nordiazepam). The techniques used for the identification were mass spectrometry, HPLC, spectrophotometry, benzodiazepine receptor binding, and immunological techniques. Benzodiazepine-like immunoreactivity was also found in all the human brains tested, including six brains that had been stored in paraffin since 1940, fifteen years before the first synthesis of benzodiazepines. These results show that benzodiazepine-like molecules of natural origin--and possibly benzodiazepines themselves--are present in human and other mammalian brains. Images PMID:3024172

Information flow between interacting human brains: Identification, validation, and relationship to social expertise.

PubMed

Bilek, Edda; Ruf, Matthias; Schäfer, Axel; Akdeniz, Ceren; Calhoun, Vince D; Schmahl, Christian; Demanuele, Charmaine; Tost, Heike; Kirsch, Peter; Meyer-Lindenberg, Andreas

2015-04-21

Social interactions are fundamental for human behavior, but the quantification of their neural underpinnings remains challenging. Here, we used hyperscanning functional MRI (fMRI) to study information flow between brains of human dyads during real-time social interaction in a joint attention paradigm. In a hardware setup enabling immersive audiovisual interaction of subjects in linked fMRI scanners, we characterize cross-brain connectivity components that are unique to interacting individuals, identifying information flow between the sender's and receiver's temporoparietal junction. We replicate these findings in an independent sample and validate our methods by demonstrating that cross-brain connectivity relates to a key real-world measure of social behavior. Together, our findings support a central role of human-specific cortical areas in the brain dynamics of dyadic interactions and provide an approach for the noninvasive examination of the neural basis of healthy and disturbed human social behavior with minimal a priori assumptions.

Translational Modeling in Schizophrenia: Predicting Human Dopamine D2 Receptor Occupancy.

PubMed

Johnson, Martin; Kozielska, Magdalena; Pilla Reddy, Venkatesh; Vermeulen, An; Barton, Hugh A; Grimwood, Sarah; de Greef, Rik; Groothuis, Geny M M; Danhof, Meindert; Proost, Johannes H

2016-04-01

To assess the ability of a previously developed hybrid physiology-based pharmacokinetic-pharmacodynamic (PBPKPD) model in rats to predict the dopamine D2 receptor occupancy (D2RO) in human striatum following administration of antipsychotic drugs. A hybrid PBPKPD model, previously developed using information on plasma concentrations, brain exposure and D2RO in rats, was used as the basis for the prediction of D2RO in human. The rat pharmacokinetic and brain physiology parameters were substituted with human population pharmacokinetic parameters and human physiological information. To predict the passive transport across the human blood-brain barrier, apparent permeability values were scaled based on rat and human brain endothelial surface area. Active efflux clearance in brain was scaled from rat to human using both human brain endothelial surface area and MDR1 expression. Binding constants at the D2 receptor were scaled based on the differences between in vitro and in vivo systems of the same species. The predictive power of this physiology-based approach was determined by comparing the D2RO predictions with the observed human D2RO of six antipsychotics at clinically relevant doses. Predicted human D2RO was in good agreement with clinically observed D2RO for five antipsychotics. Models using in vitro information predicted human D2RO well for most of the compounds evaluated in this analysis. However, human D2RO was under-predicted for haloperidol. The rat hybrid PBPKPD model structure, integrated with in vitro information and human pharmacokinetic and physiological information, constitutes a scientific basis to predict the time course of D2RO in man.

Network complexity as a measure of information processing across resting-state networks: evidence from the Human Connectome Project

PubMed Central

McDonough, Ian M.; Nashiro, Kaoru

2014-01-01

An emerging field of research focused on fluctuations in brain signals has provided evidence that the complexity of those signals, as measured by entropy, conveys important information about network dynamics (e.g., local and distributed processing). While much research has focused on how neural complexity differs in populations with different age groups or clinical disorders, substantially less research has focused on the basic understanding of neural complexity in populations with young and healthy brain states. The present study used resting-state fMRI data from the Human Connectome Project (Van Essen et al., 2013) to test the extent that neural complexity in the BOLD signal, as measured by multiscale entropy (1) would differ from random noise, (2) would differ between four major resting-state networks previously associated with higher-order cognition, and (3) would be associated with the strength and extent of functional connectivity—a complementary method of estimating information processing. We found that complexity in the BOLD signal exhibited different patterns of complexity from white, pink, and red noise and that neural complexity was differentially expressed between resting-state networks, including the default mode, cingulo-opercular, left and right frontoparietal networks. Lastly, neural complexity across all networks was negatively associated with functional connectivity at fine scales, but was positively associated with functional connectivity at coarse scales. The present study is the first to characterize neural complexity in BOLD signals at a high temporal resolution and across different networks and might help clarify the inconsistencies between neural complexity and functional connectivity, thus informing the mechanisms underlying neural complexity. PMID:24959130

Control of abdominal muscles by brain stem respiratory neurons in the cat

NASA Technical Reports Server (NTRS)

Miller, Alan D.; Ezure, Kazuhisa; Suzuki, Ichiro

1985-01-01

The nature of the control of abdominal muscles by the brain stem respiratory neurons was investigated in decerebrate unanesthetized cats. First, it was determined which of the brain stem respiratory neurons project to the lumbar cord (from which the abdominal muscles receive part of their innervation), by stimulating the neurons monopolarly. In a second part of the study, it was determined if lumbar-projecting respiratory neurons make monosynaptic connections with abdominal motoneurons; in these experiments, discriminate spontaneous spikes of antidromically acivated expiratory (E) neurons were used to trigger activity from both L1 and L2 nerves. A large projection was observed from E neurons in the caudal ventral respiratory group to the contralateral upper lumber cord. However, cross-correlation experiments found only two (out of 47 neuron pairs tested) strong monosynaptic connections between brain stem neurons and abdominal motoneurons.

Simultaneous fast measurement of circuit dynamics at multiple sites across the mammalian brain

PubMed Central

Kim, Christina K; Yang, Samuel J; Pichamoorthy, Nandini; Young, Noah P; Kauvar, Isaac; Jennings, Joshua H; Lerner, Talia N; Berndt, Andre; Lee, Soo Yeun; Ramakrishnan, Charu; Davidson, Thomas J; Inoue, Masatoshi; Bito, Haruhiko; Deisseroth, Karl

2017-01-01

Real-time activity measurements from multiple specific cell populations and projections are likely to be important for understanding the brain as a dynamical system. Here we developed frame-projected independent-fiber photometry (FIP), which we used to record fluorescence activity signals from many brain regions simultaneously in freely behaving mice. We explored the versatility of the FIP microscope by quantifying real-time activity relationships among many brain regions during social behavior, simultaneously recording activity along multiple axonal pathways during sensory experience, performing simultaneous two-color activity recording, and applying optical perturbation tuned to elicit dynamics that match naturally occurring patterns observed during behavior. PMID:26878381

MicroRNA-432 contributes to dopamine cocktail and retinoic acid induced differentiation of human neuroblastoma cells by targeting NESTIN and RCOR1 genes.

PubMed

Das, Eashita; Bhattacharyya, Nitai Pada

2014-05-02

MicroRNA (miRNA) regulates expression of protein coding genes and has been implicated in diverse cellular processes including neuronal differentiation, cell growth and death. To identify the role of miRNA in neuronal differentiation, SH-SY5Y and IMR-32 cells were treated with dopamine cocktail and retinoic acid to induce differentiation. Detection of miRNAs in differentiated cells revealed that expression of many miRNAs was altered significantly. Among the altered miRNAs, human brain expressed miR-432 induced neurite projections, arrested cells in G0-G1, reduced cell proliferation and could significantly repress NESTIN/NES, RCOR1/COREST and MECP2. Our results reveal that miR-432 regulate neuronal differentiation of human neuroblastoma cells. Copyright © 2014 Federation of European Biochemical Societies. Published by Elsevier B.V. All rights reserved.

DARPA-funded efforts in the development of novel brain-computer interface technologies.

PubMed

Miranda, Robbin A; Casebeer, William D; Hein, Amy M; Judy, Jack W; Krotkov, Eric P; Laabs, Tracy L; Manzo, Justin E; Pankratz, Kent G; Pratt, Gill A; Sanchez, Justin C; Weber, Douglas J; Wheeler, Tracey L; Ling, Geoffrey S F

2015-04-15

The Defense Advanced Research Projects Agency (DARPA) has funded innovative scientific research and technology developments in the field of brain-computer interfaces (BCI) since the 1970s. This review highlights some of DARPA's major advances in the field of BCI, particularly those made in recent years. Two broad categories of DARPA programs are presented with respect to the ultimate goals of supporting the nation's warfighters: (1) BCI efforts aimed at restoring neural and/or behavioral function, and (2) BCI efforts aimed at improving human training and performance. The programs discussed are synergistic and complementary to one another, and, moreover, promote interdisciplinary collaborations among researchers, engineers, and clinicians. Finally, this review includes a summary of some of the remaining challenges for the field of BCI, as well as the goals of new DARPA efforts in this domain. Copyright © 2014 The Authors. Published by Elsevier B.V. All rights reserved.

Brain anatomical networks in early human brain development.

PubMed

Fan, Yong; Shi, Feng; Smith, Jeffrey Keith; Lin, Weili; Gilmore, John H; Shen, Dinggang

2011-02-01

Recent neuroimaging studies have demonstrated that human brain networks have economic small-world topology and modular organization, enabling efficient information transfer among brain regions. However, it remains largely unknown how the small-world topology and modular organization of human brain networks emerge and develop. Using longitudinal MRI data of 28 healthy pediatric subjects, collected at their ages of 1 month, 1 year, and 2 years, we analyzed development patterns of brain anatomical networks derived from morphological correlations of brain regional volumes. The results show that the brain network of 1-month-olds has the characteristically economic small-world topology and nonrandom modular organization. The network's cost efficiency increases with the brain development to 1 year and 2 years, so does the modularity, providing supportive evidence for the hypothesis that the small-world topology and the modular organization of brain networks are established during early brain development to support rapid synchronization and information transfer with minimal rewiring cost, as well as to balance between local processing and global integration of information. Copyright © 2010. Published by Elsevier Inc.

Handedness- and brain size-related efficiency differences in small-world brain networks: a resting-state functional magnetic resonance imaging study.

PubMed

Li, Meiling; Wang, Junping; Liu, Feng; Chen, Heng; Lu, Fengmei; Wu, Guorong; Yu, Chunshui; Chen, Huafu

2015-05-01

The human brain has been described as a complex network, which integrates information with high efficiency. However, the relationships between the efficiency of human brain functional networks and handedness and brain size remain unclear. Twenty-one left-handed and 32 right-handed healthy subjects underwent a resting-state functional magnetic resonance imaging scan. The whole brain functional networks were constructed by thresholding Pearson correlation matrices of 90 cortical and subcortical regions. Graph theory-based methods were employed to further analyze their topological properties. As expected, all participants demonstrated small-world topology, suggesting a highly efficient topological structure. Furthermore, we found that smaller brains showed higher local efficiency, whereas larger brains showed higher global efficiency, reflecting a suitable efficiency balance between local specialization and global integration of brain functional activity. Compared with right-handers, significant alterations in nodal efficiency were revealed in left-handers, involving the anterior and median cingulate gyrus, middle temporal gyrus, angular gyrus, and amygdala. Our findings indicated that the functional network organization in the human brain was associated with handedness and brain size.

Functional atlas of the awake rat brain: A neuroimaging study of rat brain specialization and integration.

PubMed

Ma, Zhiwei; Perez, Pablo; Ma, Zilu; Liu, Yikang; Hamilton, Christina; Liang, Zhifeng; Zhang, Nanyin

2018-04-15

Connectivity-based parcellation approaches present an innovative method to segregate the brain into functionally specialized regions. These approaches have significantly advanced our understanding of the human brain organization. However, parallel progress in animal research is sparse. Using resting-state fMRI data and a novel, data-driven parcellation method, we have obtained robust functional parcellations of the rat brain. These functional parcellations reveal the regional specialization of the rat brain, which exhibited high within-parcel homogeneity and high reproducibility across animals. Graph analysis of the whole-brain network constructed based on these functional parcels indicates that the rat brain has a topological organization similar to humans, characterized by both segregation and integration. Our study also provides compelling evidence that the cingulate cortex is a functional hub region conserved from rodents to humans. Together, this study has characterized the rat brain specialization and integration, and has significantly advanced our understanding of the rat brain organization. In addition, it is valuable for studies of comparative functional neuroanatomy in mammalian brains. Copyright © 2016 Elsevier Inc. All rights reserved.

Serotonin transporter occupancy by escitalopram and citalopram in the non-human primate brain: a [(11)C]MADAM PET study.

PubMed

Finnema, Sjoerd J; Halldin, Christer; Bang-Andersen, Benny; Bundgaard, Christoffer; Farde, Lars

2015-11-01

A number of serotonin receptor positron emission tomography (PET) radioligands have been shown to be sensitive to changes in extracellular serotonin concentration, in a generalization of the well-known dopamine competition model. High doses of selective serotonin reuptake inhibitors (SSRIs) decrease serotonin receptor availability in monkey brain, consistent with increased serotonin concentrations. However, two recent studies on healthy human subjects, using a single, lower and clinically relevant SSRI dose, showed increased cortical serotonin receptor radioligand binding, suggesting potential decreases in serotonin concentration in projection regions when initiating treatment. The cross-species differential SSRI effect may be partly explained by serotonin transporter (SERT) occupancy in monkey brain being higher than is clinically relevant. We here determine SERT occupancy after single doses of escitalopram or citalopram by conducting PET measurements with [(11)C]MADAM in monkeys. Relationships between dose, plasma concentration and SERT occupancy were estimated by one-site binding analyses. Binding affinity was expressed as dose (ID50) or plasma concentration (K i) where 50 % SERT occupancy was achieved. Estimated ID50 and K i values were 0.020 mg/kg and 9.6 nmol/L for escitalopram and 0.059 mg/kg and 9.7 nmol/L for citalopram, respectively. Obtained K i values are comparable to values reported in humans. Escitalopram or citalopram doses nearly saturated SERT in previous monkey studies which examined serotonin sensitivity of receptor radioligands. PET-measured cross-species differential effects of SSRI on cortical serotonin concentration may thus be related to SSRI dose. Future monkey studies using SSRI doses inducing clinically relevant SERT occupancy may further illuminate the delayed onset of SSRI therapeutic effects.

Intranasal oxytocin, but not vasopressin, augments neural responses to toddlers in human fathers.

PubMed

Li, Ting; Chen, Xu; Mascaro, Jennifer; Haroon, Ebrahim; Rilling, James K

2017-07-01

This study investigates paternal brain function with the hope of better understanding the neural basis for variation in caregiving involvement among men. The neuropeptides oxytocin (OT) and vasopressin (AVP) are implicated in paternal caregiving in humans and other species. In a double-blind, placebo-controlled, within-subject pharmaco-functional MRI experiment, we randomized 30 fathers of 1-2year old children to receive either 24IU intranasal OT before one scan and placebo before the other scan (n=15) or 20IU intranasal AVP before one scan and placebo before the other scan (n=15). Brain function was measured with fMRI as the fathers viewed pictures of their children, unknown children and unknown adults, and as they listened to unknown infant cry stimuli. Intranasal OT, but not AVP, significantly increased the BOLD fMRI response to viewing pictures of own children within the caudate nucleus, a target of midbrain dopamine projections, as well as the dorsal anterior cingulate (dACC) and visual cortex, suggesting that intranasal oxytocin augments activation in brain regions involved in reward, empathy and attention in human fathers. OT effects also varied as a function of order of administration such that when OT was given before placebo, it increased activation within several reward-related structures (substantia nigra, ventral tegmental area, putamen) more than when it was given after placebo. Neither OT nor AVP had significant main effects on the neural response to cries. Our findings suggest that the hormonal changes associated with the transition to fatherhood are likely to facilitate increased approach motivation and empathy for children, and call for future research that evaluates the potential of OT to normalize deficits in paternal motivation, as might be found among men suffering from post-partum depression. Copyright © 2017 Elsevier Inc. All rights reserved.

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

NASA Astrophysics Data System (ADS)

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

2014-03-01

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

Preclinical Characterization of 18F-MK-6240, a Promising PET Tracer for In Vivo Quantification of Human Neurofibrillary Tangles.

PubMed

Hostetler, Eric D; Walji, Abbas M; Zeng, Zhizhen; Miller, Patricia; Bennacef, Idriss; Salinas, Cristian; Connolly, Brett; Gantert, Liza; Haley, Hyking; Holahan, Marie; Purcell, Mona; Riffel, Kerry; Lohith, Talakad G; Coleman, Paul; Soriano, Aileen; Ogawa, Aimie; Xu, Serena; Zhang, Xiaoping; Joshi, Elizabeth; Della Rocca, Joseph; Hesk, David; Schenk, David J; Evelhoch, Jeffrey L

2016-10-01

A PET tracer is desired to help guide the discovery and development of disease-modifying therapeutics for neurodegenerative diseases characterized by neurofibrillary tangles (NFTs), the predominant tau pathology in Alzheimer disease (AD). We describe the preclinical characterization of the NFT PET tracer 18 F-MK-6240. In vitro binding studies were conducted with 3 H-MK-6240 in tissue slices and homogenates from cognitively normal and AD human brain donors to evaluate tracer affinity and selectivity for NFTs. Immunohistochemistry for phosphorylated tau was performed on human brain slices for comparison with 3 H-MK-6240 binding patterns on adjacent brain slices. PET studies were performed with 18 F-MK-6240 in monkeys to evaluate tracer kinetics and distribution in the brain. 18 F-MK-6240 monkey PET studies were conducted after dosing with unlabeled MK-6240 to evaluate tracer binding selectivity in vivo. The 3 H-MK-6240 binding pattern was consistent with the distribution of phosphorylated tau in human AD brain slices. 3 H-MK-6240 bound with high affinity to human AD brain cortex homogenates containing abundant NFTs but bound poorly to amyloid plaque-rich, NFT-poor AD brain homogenates. 3 H-MK-6240 showed no displaceable binding in the subcortical regions of human AD brain slices and in the hippocampus/entorhinal cortex of non-AD human brain homogenates. In monkey PET studies, 18 F-MK-6240 displayed rapid and homogeneous distribution in the brain. The 18 F-MK-6240 volume of distribution stabilized rapidly, indicating favorable tracer kinetics. No displaceable binding was observed in self-block studies in rhesus monkeys, which do not natively express NFTs. Moderate defluorination was observed as skull uptake. 18 F-MK-6240 is a promising PET tracer for the in vivo quantification of NFTs in AD patients. © 2016 by the Society of Nuclear Medicine and Molecular Imaging, Inc.

A Celebration of Neurons: An Educator's Guide to the Human Brain.

ERIC Educational Resources Information Center

Sylwester, Robert

This book provides an introduction to the current scientific understanding of the human brain and its processes. Chapter 1, "At the Edge of a Major Transformation," is an introduction to the field. Chapter 2, "How Our Brain Organizes Itself on the Cellular and Systems Levels," covers what body/brain cellular systems do, how…

Neuroscience Club in SKKK3 and SMSTMFP: The Brain Apprentice Project.

PubMed

Mohd Ibrahim, Seri Dewi; Muda, Mazinah

2015-01-01

Sekolah Menengah Sains Tengku Muhammad Faris Petra (SMSTMFP) and Sekolah Kebangsaan Kubang Kerian (3) (SKKK3) were selected by the Department of Neurosciences, Universiti Sains Malaysia (USM), in 2011 to be a 'school-based Neuroscience Club' via the 'Knowledge Transfer Programme (KTP) - Community' project. This community project was known as "The Brain Apprentice Project". The objectives of this project were to promote science and the neurosciences beyond conventional classroom teachings whilst guiding creativity and innovation as well as to assist in the delivery of neuroscience knowledge through graduate interns as part of the cultivation of neuroscience as a fruitful future career option. All of the planned club activities moulded the students to be knowledgeable individuals with admirable leadership skills, which will help the schools produce more scientists, technocrats and professionals who can fulfil the requirements of our religion, race and nation in the future. Some of the activities carried out over the years include the "My Brain Invention Competition", "Mini Brain Bee Contest", "Recycled Melody" and "Brain Dissection". These activities educated the students well and improved their confidence levels in their communication and soft skills. The participation of the students in international-level competition, such as the "International Brain Bee", was one of the ways future professionals were created for the nation. The implementation of Neuroscience Club as one of the organisations in the school's cocurriculum was an appropriate step in transferring science and neuroscience knowledge and skills from a higher education institution, namely USM, to both of the schools, SMSTMFP and SKKK3. The club members showed great interest in all of the club's activities and their performance on the Ujian Pencapaian Sekolah Rendah (UPSR) or Primary School Achievement Test and Sijil Pelajaran Malaysia (SPM) or Malaysian Certificate of Education examinations improved tremendously.

Human brain activity with functional NIR optical imager

NASA Astrophysics Data System (ADS)

Luo, Qingming

2001-08-01

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

A multisample study of longitudinal changes in brain network architecture in 4-13-year-old children.

PubMed

Wierenga, Lara M; van den Heuvel, Martijn P; Oranje, Bob; Giedd, Jay N; Durston, Sarah; Peper, Jiska S; Brown, Timothy T; Crone, Eveline A

2018-01-01

Recent advances in human neuroimaging research have revealed that white-matter connectivity can be described in terms of an integrated network, which is the basis of the human connectome. However, the developmental changes of this connectome in childhood are not well understood. This study made use of two independent longitudinal diffusion-weighted imaging data sets to characterize developmental changes in the connectome by estimating age-related changes in fractional anisotropy (FA) for reconstructed fibers (edges) between 68 cortical regions. The first sample included 237 diffusion-weighted scans of 146 typically developing children (4-13 years old, 74 females) derived from the Pediatric Longitudinal Imaging, Neurocognition, and Genetics (PLING) study. The second sample included 141 scans of 97 individuals (8-13 years old, 62 females) derived from the BrainTime project. In both data sets, we compared edges that had the most substantial age-related change in FA to edges that showed little change in FA. This allowed us to investigate if developmental changes in white matter reorganize network topology. We observed substantial increases in edges connecting peripheral and a set of highly connected hub regions, referred to as the rich club. Together with the observed topological differences between regions connecting to edges showing the smallest and largest changes in FA, this indicates that changes in white matter affect network organization, such that highly connected regions become even more strongly imbedded in the network. These findings suggest that an important process in brain development involves organizing patterns of inter-regional interactions. Hum Brain Mapp 39:157-170, 2018. © 2017 Wiley Periodicals, Inc. © 2017 Wiley Periodicals, Inc.

I-123 - FP-CIT pharmacokinetics and dosimetry show great potential for the evaluation of dopamine transporter system in clinical routine

DOE Office of Scientific and Technical Information (OSTI.GOV)

Costa, D.C.; Walker, S.; Waddington, W.

1996-05-01

FP-CIT is a N-fluoropropyl analogue of the [2{beta}-carbomethoxy-3{beta}-(4-iodophenyl)tropane] which has been labelled with I-123 and developed as a new marker of the pre-synaptic dopamine transporter system. Its selective uptake in the striatum of non-human primates and human volunteers has been reported with advantageous faster brain kinetics than {beta}-CIT. In this pilot work we studied the whole body imaging kinetics of FP-CIT in one normal volunteer - NV (5, 60, 100, 360 minutes and 24 hours post-injection for 20 minutes each) and a drug-free patient with well established Parkinson`s disease - PD (100 minutes) after intravenous injection of 111 MBq. Bothmore » subjects had high resolution brain SPECT at 35 minutes and 3.5 hours post-injection. Percent of whole body uptake (geometric mean of anterior and posterior projections) in different organs, including total brain and basal ganglia shows rapid clearance from blood during the first hour with no significant change from 100 minutes to 24 hours. The basal ganglia uptake is approximately 0.4% of total body from 100 minutes onwards. Striatal uptake (ratio to frontal cortex) is different between subjects, mainly at 3.5 hours and more marked in the putamen: Calculated dosimetry (mSv/MBq) showed E.D.E.-0.034, and total doses to whole body - 0.01, total brain - 0.017, basal ganglia - 0.155, small intestine - 0.06, urinary bladder - 0.05 and liver - 0.03. These data confirm that FP-CIT has acceptable dosimetry with good pharmacokinetics enabling the study of pre-synaptic dopamine transport system in nigrostriatal degeneration with clinical SPECT at 3-4 hrs p.i.« less

Cognitive neuroscience 2.0: building a cumulative science of human brain function

PubMed Central

Yarkoni, Tal; Poldrack, Russell A.; Van Essen, David C.; Wager, Tor D.

2010-01-01

Cognitive neuroscientists increasingly recognize that continued progress in understanding human brain function will require not only the acquisition of new data, but also the synthesis and integration of data across studies and laboratories. Here we review ongoing efforts to develop a more cumulative science of human brain function. We discuss the rationale for an increased focus on formal synthesis of the cognitive neuroscience literature, provide an overview of recently developed tools and platforms designed to facilitate the sharing and integration of neuroimaging data, and conclude with a discussion of several emerging developments that hold even greater promise in advancing the study of human brain function. PMID:20884276

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

PubMed Central

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

2015-01-01

The advantages of high-resolution diffusion tensor imaging (DTI) have been demonstrated in a recent post-mortem human brain study (Miller et al., NeuroImage 2011;57(1):167–181), showing that white matter fiber tracts can be much more accurately detected in data at submillimeter isotropic resolution. To our knowledge, in vivo human brain DTI at submillimeter isotropic resolution has not been routinely achieved yet because of the difficulty in simultaneously achieving high resolution and high signal-to-noise ratio (SNR) in DTI scans. Here we report a 3D multi-slab interleaved EPI acquisition integrated with multiplexed sensitivity encoded (MUSE) reconstruction, to achieve high-quality, high-SNR and submillimeter isotropic resolution (0.85 × 0.85 × 0.85 mm3) in vivo human brain DTI on a 3 Tesla clinical MRI scanner. In agreement with the previously reported post-mortem human brain DTI study, our in vivo data show that the structural connectivity networks of human brains can be mapped more accurately and completely with high-resolution DTI as compared with conventional DTI (e.g., 2 × 2 × 2 mm3). PMID:26072250

Brain tumor segmentation based on local independent projection-based classification.

PubMed

Huang, Meiyan; Yang, Wei; Wu, Yao; Jiang, Jun; Chen, Wufan; Feng, Qianjin

2014-10-01

Brain tumor segmentation is an important procedure for early tumor diagnosis and radiotherapy planning. Although numerous brain tumor segmentation methods have been presented, enhancing tumor segmentation methods is still challenging because brain tumor MRI images exhibit complex characteristics, such as high diversity in tumor appearance and ambiguous tumor boundaries. To address this problem, we propose a novel automatic tumor segmentation method for MRI images. This method treats tumor segmentation as a classification problem. Additionally, the local independent projection-based classification (LIPC) method is used to classify each voxel into different classes. A novel classification framework is derived by introducing the local independent projection into the classical classification model. Locality is important in the calculation of local independent projections for LIPC. Locality is also considered in determining whether local anchor embedding is more applicable in solving linear projection weights compared with other coding methods. Moreover, LIPC considers the data distribution of different classes by learning a softmax regression model, which can further improve classification performance. In this study, 80 brain tumor MRI images with ground truth data are used as training data and 40 images without ground truth data are used as testing data. The segmentation results of testing data are evaluated by an online evaluation tool. The average dice similarities of the proposed method for segmenting complete tumor, tumor core, and contrast-enhancing tumor on real patient data are 0.84, 0.685, and 0.585, respectively. These results are comparable to other state-of-the-art methods.

On the nature and evolution of the neural bases of human language

NASA Technical Reports Server (NTRS)

Lieberman, Philip

2002-01-01

The traditional theory equating the brain bases of language with Broca's and Wernicke's neocortical areas is wrong. Neural circuits linking activity in anatomically segregated populations of neurons in subcortical structures and the neocortex throughout the human brain regulate complex behaviors such as walking, talking, and comprehending the meaning of sentences. When we hear or read a word, neural structures involved in the perception or real-world associations of the word are activated as well as posterior cortical regions adjacent to Wernicke's area. Many areas of the neocortex and subcortical structures support the cortical-striatal-cortical circuits that confer complex syntactic ability, speech production, and a large vocabulary. However, many of these structures also form part of the neural circuits regulating other aspects of behavior. For example, the basal ganglia, which regulate motor control, are also crucial elements in the circuits that confer human linguistic ability and abstract reasoning. The cerebellum, traditionally associated with motor control, is active in motor learning. The basal ganglia are also key elements in reward-based learning. Data from studies of Broca's aphasia, Parkinson's disease, hypoxia, focal brain damage, and a genetically transmitted brain anomaly (the putative "language gene," family KE), and from comparative studies of the brains and behavior of other species, demonstrate that the basal ganglia sequence the discrete elements that constitute a complete motor act, syntactic process, or thought process. Imaging studies of intact human subjects and electrophysiologic and tracer studies of the brains and behavior of other species confirm these findings. As Dobzansky put it, "Nothing in biology makes sense except in the light of evolution" (cited in Mayr, 1982). That applies with as much force to the human brain and the neural bases of language as it does to the human foot or jaw. The converse follows: the mark of evolution on the brains of human beings and other species provides insight into the evolution of the brain bases of human language. The neural substrate that regulated motor control in the common ancestor of apes and humans most likely was modified to enhance cognitive and linguistic ability. Speech communication played a central role in this process. However, the process that ultimately resulted in the human brain may have started when our earliest hominid ancestors began to walk.

Revealing topological organization of human brain functional networks with resting-state functional near infrared spectroscopy.

PubMed

Niu, Haijing; Wang, Jinhui; Zhao, Tengda; Shu, Ni; He, Yong

2012-01-01

The human brain is a highly complex system that can be represented as a structurally interconnected and functionally synchronized network, which assures both the segregation and integration of information processing. Recent studies have demonstrated that a variety of neuroimaging and neurophysiological techniques such as functional magnetic resonance imaging (MRI), diffusion MRI and electroencephalography/magnetoencephalography can be employed to explore the topological organization of human brain networks. However, little is known about whether functional near infrared spectroscopy (fNIRS), a relatively new optical imaging technology, can be used to map functional connectome of the human brain and reveal meaningful and reproducible topological characteristics. We utilized resting-state fNIRS (R-fNIRS) to investigate the topological organization of human brain functional networks in 15 healthy adults. Brain networks were constructed by thresholding the temporal correlation matrices of 46 channels and analyzed using graph-theory approaches. We found that the functional brain network derived from R-fNIRS data had efficient small-world properties, significant hierarchical modular structure and highly connected hubs. These results were highly reproducible both across participants and over time and were consistent with previous findings based on other functional imaging techniques. Our results confirmed the feasibility and validity of using graph-theory approaches in conjunction with optical imaging techniques to explore the topological organization of human brain networks. These results may expand a methodological framework for utilizing fNIRS to study functional network changes that occur in association with development, aging and neurological and psychiatric disorders.

Localization of migraine susceptibility genes in human brain by single-cell RNA sequencing.

PubMed

Renthal, William

2018-01-01

Background Migraine is a debilitating disorder characterized by severe headaches and associated neurological symptoms. A key challenge to understanding migraine has been the cellular complexity of the human brain and the multiple cell types implicated in its pathophysiology. The present study leverages recent advances in single-cell transcriptomics to localize the specific human brain cell types in which putative migraine susceptibility genes are expressed. Methods The cell-type specific expression of both familial and common migraine-associated genes was determined bioinformatically using data from 2,039 individual human brain cells across two published single-cell RNA sequencing datasets. Enrichment of migraine-associated genes was determined for each brain cell type. Results Analysis of single-brain cell RNA sequencing data from five major subtypes of cells in the human cortex (neurons, oligodendrocytes, astrocytes, microglia, and endothelial cells) indicates that over 40% of known migraine-associated genes are enriched in the expression profiles of a specific brain cell type. Further analysis of neuronal migraine-associated genes demonstrated that approximately 70% were significantly enriched in inhibitory neurons and 30% in excitatory neurons. Conclusions This study takes the next step in understanding the human brain cell types in which putative migraine susceptibility genes are expressed. Both familial and common migraine may arise from dysfunction of discrete cell types within the neurovascular unit, and localization of the affected cell type(s) in an individual patient may provide insight into to their susceptibility to migraine.

Deconstructing the Brain Disconnection–Brain Death Analogy and Clarifying the Rationale for the Neurological Criterion of Death

PubMed Central

Moschella, Melissa

2016-01-01

This article explains the problems with Alan Shewmon’s critique of brain death as a valid sign of human death, beginning with a critical examination of his analogy between brain death and severe spinal cord injury. The article then goes on to assess his broader argument against the necessity of the brain for adult human organismal integration, arguing that he fails to translate correctly from biological to metaphysical claims. Finally, on the basis of a deeper metaphysical analysis, I offer a revised rationale for the validity of the neurological criterion of human death. PMID:27095749

MRI with intrathecal MRI gadolinium contrast medium administration: a possible method to assess glymphatic function in human brain.

PubMed

Eide, Per Kristian; Ringstad, Geir

2015-11-01

Recently, the "glymphatic system" of the brain has been discovered in rodents, which is a paravascular, transparenchymal route for clearance of excess brain metabolites and distribution of compounds in the cerebrospinal fluid. It has already been demonstrated that intrathecally administered gadolinium (Gd) contrast medium distributes along this route in rats, but so far not in humans. A 27-year-old woman underwent magnetic resonance imaging (MRI) with intrathecal administration of gadobutrol, which distributed throughout her entire brain after 1 and 4.5 h. MRI with intrathecal Gd may become a tool to study glymphatic function in the human brain.

X-ray diffraction evidence for myelin disorder in brain from humans with Alzheimer's disease.

PubMed

Chia, L S; Thompson, J E; Moscarello, M A

1984-09-05

Wide-angle X-ray diffraction studies revealed that the lipid phase transition temperature of myelin from brain tissue of humans with Alzheimer's disease was about 12 degrees C lower than that of normal age-matched controls, indicating differences in the physical organization of the myelin lipid bilayer. Elevated levels of malondialdehyde and conjugated diene were found in brain tissue from humans with Alzheimer's disease, indicating an increased amount of lipid peroxidation over the controls. An increase in myelin disorder and in lipid peroxidation can both be correlated with aging in human brain, but the changes in myelin from humans with Alzheimer's disease are more pronounced than in normal aging. These changes might represent severe or accelerated aging.

Molecular networks and the evolution of human cognitive specializations.

PubMed

Fontenot, Miles; Konopka, Genevieve

2014-12-01

Inroads into elucidating the origins of human cognitive specializations have taken many forms, including genetic, genomic, anatomical, and behavioral assays that typically compare humans to non-human primates. While the integration of all of these approaches is essential for ultimately understanding human cognition, here, we review the usefulness of coexpression network analysis for specifically addressing this question. An increasing number of studies have incorporated coexpression networks into brain expression studies comparing species, disease versus control tissue, brain regions, or developmental time periods. A clearer picture has emerged of the key genes driving brain evolution, as well as the developmental and regional contributions of gene expression patterns important for normal brain development and those misregulated in cognitive diseases. Copyright © 2014 Elsevier Ltd. All rights reserved.

Human brain spots emotion in non humanoid robots

PubMed Central

Foucher, Aurélie; Jouvent, Roland; Nadel, Jacqueline

2011-01-01

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

Total Brain Death and the Integration of the Body Required of a Human Being

PubMed Central

Lee, Patrick

2016-01-01

I develop and refine an argument for the total brain death criterion of death previously advanced by Germain Grisez and me: A human being is essentially a rational animal, and so must have a radical capacity for rational operations. For rational animals, conscious sensation is a pre-requisite for rational operation. But total brain death results in the loss of the radical capacity for conscious sensation, and so also for rational operations. Hence, total brain death constitutes a substantial change—the ceasing to be of the human being. Objections are considered, including the objection that total brain death need not result in the loss of capacity for sensation, and that damage to the brain less than total brain death can result in loss of capacity for rational operations. PMID:27097647

Impact of Neurodegenerative Diseases on Drug Binding to Brain Tissues: From Animal Models to Human Samples.

PubMed

Ugarte, Ana; Corbacho, David; Aymerich, María S; García-Osta, Ana; Cuadrado-Tejedor, Mar; Oyarzabal, Julen

2018-04-19

Drug efficacy in the central nervous system (CNS) requires an additional step after crossing the blood-brain barrier. Therapeutic agents must reach their targets in the brain to modulate them; thus, the free drug concentration hypothesis is a key parameter for in vivo pharmacology. Here, we report the impact of neurodegeneration (Alzheimer's disease (AD) and Parkinson's disease (PD) compared with healthy controls) on the binding of 10 known drugs to postmortem brain tissues from animal models and humans. Unbound drug fractions, for some drugs, are significantly different between healthy and injured brain tissues (AD or PD). In addition, drugs binding to brain tissues from AD and PD animal models do not always recapitulate their binding to the corresponding human injured brain tissues. These results reveal potentially relevant implications for CNS drug discovery.

Use of high-radiant flux, high-resolution DMD light engines in industrial applications

NASA Astrophysics Data System (ADS)

Müller, Alexandra; Ram, Surinder

2014-03-01

The field of application of industrial projectors is growing day by day. New Digital Micromirror Device (DMD) - based applications like 3D printing, 3D scanning, Printed Circuit Board (PCB) board printing and others are getting more and more sophisticated. The technical demands for the projection system are rising as new and more stringent requirements appear. The specification for industrial projection systems differ substantially from the ones of business and home beamers. Beamers are designed to please the human eye. Bright colors and image enhancement are far more important than uniformity of the illumination or image distortion. The human eye, followed by the processing of the brain can live with quite high intensity variations on the screen and image distortion. On the other hand, a projector designed for use in a specialized field has to be tailored regarding its unique requirements in order to make no quality compromises. For instance, when the image is projected onto a light sensitive resin, a good uniformity of the illumination is crucial for good material hardening (curing) results. The demands on the hardware and software are often very challenging. In the following we will review some parameters that have to be considered carefully for the design of industrial projectors in order to get the optimum result without compromises.

CoCoMac 2.0 and the future of tract-tracing databases

PubMed Central

Bakker, Rembrandt; Wachtler, Thomas; Diesmann, Markus

2012-01-01

The CoCoMac database contains the results of several hundred published axonal tract-tracing studies in the macaque monkey brain. The combined results are used for constructing the macaque macro-connectome. Here we discuss the redevelopment of CoCoMac and compare it to six connectome-related projects: two online resources that provide full access to raw tracing data in rodents, a connectome viewer for advanced 3D graphics, a partial but highly detailed rat connectome, a brain data management system that generates custom connectivity matrices, and a software package that covers the complete pipeline from connectivity data to large-scale brain simulations. The second edition of CoCoMac features many enhancements over the original. For example, a search wizard is provided for full access to all tables and their nested dependencies. Connectivity matrices can be computed on demand in a user-selected nomenclature. A new data entry system is available as a preview, and is to become a generic solution for community-driven data entry in manually collated databases. We conclude with the question whether neuronal tracing will remain the gold standard to uncover the wiring of brains, thereby highlighting developments in human connectome construction, tracer substances, polarized light imaging, and serial block-face scanning electron microscopy. PMID:23293600

CoCoMac 2.0 and the future of tract-tracing databases.

PubMed

Bakker, Rembrandt; Wachtler, Thomas; Diesmann, Markus

2012-01-01

The CoCoMac database contains the results of several hundred published axonal tract-tracing studies in the macaque monkey brain. The combined results are used for constructing the macaque macro-connectome. Here we discuss the redevelopment of CoCoMac and compare it to six connectome-related projects: two online resources that provide full access to raw tracing data in rodents, a connectome viewer for advanced 3D graphics, a partial but highly detailed rat connectome, a brain data management system that generates custom connectivity matrices, and a software package that covers the complete pipeline from connectivity data to large-scale brain simulations. The second edition of CoCoMac features many enhancements over the original. For example, a search wizard is provided for full access to all tables and their nested dependencies. Connectivity matrices can be computed on demand in a user-selected nomenclature. A new data entry system is available as a preview, and is to become a generic solution for community-driven data entry in manually collated databases. We conclude with the question whether neuronal tracing will remain the gold standard to uncover the wiring of brains, thereby highlighting developments in human connectome construction, tracer substances, polarized light imaging, and serial block-face scanning electron microscopy.

Safe, efficient, and reproducible gene therapy of the brain in the dog models of Sanfilippo and Hurler syndromes.

PubMed

Ellinwood, N Matthew; Ausseil, Jérôme; Desmaris, Nathalie; Bigou, Stéphanie; Liu, Song; Jens, Jackie K; Snella, Elizabeth M; Mohammed, Eman E A; Thomson, Christopher B; Raoul, Sylvie; Joussemet, Béatrice; Roux, Françoise; Chérel, Yan; Lajat, Yaouen; Piraud, Monique; Benchaouir, Rachid; Hermening, Stephan; Petry, Harald; Froissart, Roseline; Tardieu, Marc; Ciron, Carine; Moullier, Philippe; Parkes, Jennifer; Kline, Karen L; Maire, Irène; Vanier, Marie-Thérèse; Heard, Jean-Michel; Colle, Marie-Anne

2011-02-01

Recent trials in patients with neurodegenerative diseases documented the safety of gene therapy based on adeno-associated virus (AAV) vectors deposited into the brain. Inborn errors of the metabolism are the most frequent causes of neurodegeneration in pre-adulthood. In Sanfilippo syndrome, a lysosomal storage disease in which heparan sulfate oligosaccharides accumulate, the onset of clinical manifestation is before 5 years. Studies in the mouse model showed that gene therapy providing the missing enzyme α-N-acetyl-glucosaminidase to brain cells prevents neurodegeneration and improves behavior. We now document safety and efficacy in affected dogs. Animals received eight deposits of a serotype 5 AAV vector, including vector prepared in insect Sf9 cells. As shown previously in dogs with the closely related Hurler syndrome, immunosuppression was necessary to prevent neuroinflammation and elimination of transduced cells. In immunosuppressed dogs, vector was efficiently delivered throughout the brain, induced α-N-acetyl-glucosaminidase production, cleared stored compounds and storage lesions. The suitability of the procedure for clinical application was further assessed in Hurler dogs, providing information on reproducibility, tolerance, appropriate vector type and dosage, and optimal age for treatment in a total number of 25 treated dogs. Results strongly support projects of human trials aimed at assessing this treatment in Sanfilippo syndrome.

Visualization of migration of human cortical neurons generated from induced pluripotent stem cells.

PubMed

Bamba, Yohei; Kanemura, Yonehiro; Okano, Hideyuki; Yamasaki, Mami

2017-09-01

Neuronal migration is considered a key process in human brain development. However, direct observation of migrating human cortical neurons in the fetal brain is accompanied by ethical concerns and is a major obstacle in investigating human cortical neuronal migration. We established a novel system that enables direct visualization of migrating cortical neurons generated from human induced pluripotent stem cells (hiPSCs). We observed the migration of cortical neurons generated from hiPSCs derived from a control and from a patient with lissencephaly. Our system needs no viable brain tissue, which is usually used in slice culture. Migratory behavior of human cortical neuron can be observed more easily and more vividly by its fluorescence and glial scaffold than that by earlier methods. Our in vitro experimental system provides a new platform for investigating development of the human central nervous system and brain malformation. Copyright © 2017 Elsevier B.V. All rights reserved.

A Study on Analysis of EEG Caused by Grating Stimulation Imaging

NASA Astrophysics Data System (ADS)

Urakawa, Hiroshi; Nishimura, Toshihiro; Tsubai, Masayoshi; Itoh, Kenji

Recently, many researchers have studied a visual perception. Focus is attended to studies of the visual perception phenomenon by using the grating stimulation images. The previous researches have suggested that a subset of retinal ganglion cells responds to motion in the receptive field center, but only if the wider surround moves with a different trajectory. We discuss the function of human retina, and measure and analysis EEG(electroencephalography) of a normal subject who looks on grating stimulation images. We confirmed the visual perception of human by EEG signal analysis. We also have obtained that a sinusoidal grating stimulation was given, asymmetry was observed the α wave element in EEG of the symmetric part in a left hemisphere and a right hemisphere of the brain. Therefore, it is presumed that projected image is even when the still picture is seen and the image projected onto retinas of right and left eyes is not even for the dynamic scene. It evaluated it by taking the envelope curve for the detected α wave, and using the average and standard deviation.

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

PubMed

Mavridis, Ioannis N; Pyrgelis, Efstratios-Stylianos

2016-03-01

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

75 FR 64986 - Marine Mammals; File No. 14525

Federal Register 2010, 2011, 2012, 2013, 2014

2010-10-21

... captivity, sampled while in captivity, and euthanized at the termination of study to obtain their brains. Whole brains and brain tissues will be imported to the U.S. for anatomical and immunohistochemical studies. The first aim of the project is to correlate the release of major neurotransmitters in the brain...

Time-resolved fluorescence spectroscopy of human brain tumors

NASA Astrophysics Data System (ADS)

Marcu, Laura; Thompson, Reid C.; Garde, Smita; Sedrak, Mark; Black, Keith L.; Yong, William H.

2002-05-01

Fluorescence spectroscopy of the endogenous emission of brain tumors has been researched as a potentially important method for the intraoperative localization of brain tumor margins. In this study, we investigate the use of time-resolved laser-induced fluorescence spectroscopy (TR-LIFS) for demarcation of primary brain tumors by studying the time-resolved spectra of gliomas of different histologic grades. Time-resolved fluorescence (3 ns, 337 nm excitation) from excised human brain tumor show differences between the time-resolved emission of malignant glioma and normal brain tissue (gray and white matter). Our findings suggest that brain tumors can be differentiated from normal brain tissue based upon unique time-resolved fluorescence signature.

Multilayer modeling and analysis of human brain networks

PubMed Central

2017-01-01

Abstract Understanding how the human brain is structured, and how its architecture is related to function, is of paramount importance for a variety of applications, including but not limited to new ways to prevent, deal with, and cure brain diseases, such as Alzheimer’s or Parkinson’s, and psychiatric disorders, such as schizophrenia. The recent advances in structural and functional neuroimaging, together with the increasing attitude toward interdisciplinary approaches involving computer science, mathematics, and physics, are fostering interesting results from computational neuroscience that are quite often based on the analysis of complex network representation of the human brain. In recent years, this representation experienced a theoretical and computational revolution that is breaching neuroscience, allowing us to cope with the increasing complexity of the human brain across multiple scales and in multiple dimensions and to model structural and functional connectivity from new perspectives, often combined with each other. In this work, we will review the main achievements obtained from interdisciplinary research based on magnetic resonance imaging and establish de facto, the birth of multilayer network analysis and modeling of the human brain. PMID:28327916

Expansion of Multipotent Stem Cells from the Adult Human Brain

PubMed Central

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

2013-01-01

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

A Novel Closed-Head Model of Mild Traumatic Brain Injury Caused by Primary Overpressure Blast to the Cranium Produces Sustained Emotional Deficits in Mice

PubMed Central

Heldt, Scott A.; Elberger, Andrea J.; Deng, Yunping; Guley, Natalie H.; Del Mar, Nobel; Rogers, Joshua; Choi, Gy Won; Ferrell, Jessica; Rex, Tonia S.; Honig, Marcia G.; Reiner, Anton

2014-01-01

Emotional disorders are a common outcome from mild traumatic brain injury (TBI) in humans, but their pathophysiological basis is poorly understood. We have developed a mouse model of closed-head blast injury using an air pressure wave delivered to a small area on one side of the cranium, to create mild TBI. We found that 20-psi blasts in 3-month-old C57BL/6 male mice yielded no obvious behavioral or histological evidence of brain injury, while 25–40 psi blasts produced transient anxiety in an open field arena but little histological evidence of brain damage. By contrast, 50–60 psi blasts resulted in anxiety-like behavior in an open field arena that became more evident with time after blast. In additional behavioral tests conducted 2–8 weeks after blast, 50–60 psi mice also demonstrated increased acoustic startle, perseverance of learned fear, and enhanced contextual fear, as well as depression-like behavior and diminished prepulse inhibition. We found no evident cerebral pathology, but did observe scattered axonal degeneration in brain sections from 50 to 60 psi mice 3–8 weeks after blast. Thus, the TBI caused by single 50–60 psi blasts in mice exhibits the minimal neuronal loss coupled to “diffuse” axonal injury characteristic of human mild TBI. A reduction in the abundance of a subpopulation of excitatory projection neurons in basolateral amygdala enriched in Thy1 was, however, observed. The reported link of this neuronal population to fear suppression suggests their damage by mild TBI may contribute to the heightened anxiety and fearfulness observed after blast in our mice. Our overpressure air blast model of concussion in mice will enable further studies of the mechanisms underlying the diverse emotional deficits seen after mild TBI. PMID:24478749

Tissue and organ donation for research in forensic pathology: the MRC Sudden Death Brain and Tissue Bank.

PubMed

Millar, T; Walker, R; Arango, J-C; Ironside, J W; Harrison, D J; MacIntyre, D J; Blackwood, D; Smith, C; Bell, J E

2007-12-01

Novel methodological approaches to the investigation of brain and non-central nervous system disorders have led to increased demand for well-characterized, high quality human tissue samples, particularly from control cases. In the setting of the new Human Tissue legislation, we sought to determine whether relatives who have been suddenly bereaved are willing to grant authorization for research use of post mortem tissue samples and organs in sufficient numbers to support the establishment of a brain and tissue bank based in the forensic service. Research authorization was sought from families on the day prior to forensic post mortem examination followed up by written confirmation. We have to date selected individuals who have died suddenly (age range 1-89 years) and who were likely to have normal brains or who had displayed symptoms of a CNS disorder of interest to researchers, including psychiatric disorders. One hundred and eleven families have been approached during the first 2 years of this project. Research use of tissue samples was authorized by 96% of families and 17% agreed to whole brain donation. Audit of families' experience does not suggest that they are further distressed by being approached. Respondents expressed a clear view that the opportunity for research donation should be open to all bereaved families. Despite the sometimes long post mortem intervals, the quality of tissue samples is good, as assessed by a range of markers including Agilent BioAnalyzer quantification of RNA integrity (mean value 6.4). We conclude that the vast majority of families are willing to support research use of post mortem tissues even in the context of sudden bereavement and despite previous adverse publicity. The potential for acquisition of normal CNS and non-CNS tissues and of various hard-to-get CNS disorders suggests that efforts to access the forensic post mortem service for research material are eminently worthwhile. (c) 2007 Pathological Society of Great Britain and Ireland

Issues of exploration: human health and wellbeing during a mission to Mars.

PubMed

White, R J; Bassingthwaighte, J B; Charles, J B; Kushmerick, M J; Newman, D J

2003-01-01

Today, the tools are in our hands to enable us to travel away from our home planet and become citizens of the solar system. Even now, we are seriously beginning to develop the robust infrastructure that will make the 21st century the Century of Space Travel. But this bold step must be taken with due concern for the health, safety and wellbeing of future space explorers. Our long experience with space biomedical research convinces us that, if we are to deal effectively with the medical and biomedical issues of exploration, then dramatic and bold steps are also necessary in this field. We can no longer treat the human body as if it were composed of muscles, bones, heart and brain acting independently. Instead, we must lead the effort to develop a fully integrated view of the body, with all parts connected and fully interacting in a realistic way. This paper will present the status of current (2000) plans by the National Space Biomedical Research Institute to initiate research in this area of integrative physiology and medicine. Specifically, three example projects are discussed as potential stepping stones towards the ultimate goal of producing a digital human. These projects relate to developing a functional model of the human musculoskeletal system and the heart. c2002 COSPAR. Published by Elsevier Science Ltd. All rights reserved.

Issues of exploration: human health and wellbeing during a mission to Mars

NASA Technical Reports Server (NTRS)

White, R. J.; Bassingthwaighte, J. B.; Charles, J. B.; Kushmerick, M. J.; Newman, D. J.

2003-01-01

Today, the tools are in our hands to enable us to travel away from our home planet and become citizens of the solar system. Even now, we are seriously beginning to develop the robust infrastructure that will make the 21st century the Century of Space Travel. But this bold step must be taken with due concern for the health, safety and wellbeing of future space explorers. Our long experience with space biomedical research convinces us that, if we are to deal effectively with the medical and biomedical issues of exploration, then dramatic and bold steps are also necessary in this field. We can no longer treat the human body as if it were composed of muscles, bones, heart and brain acting independently. Instead, we must lead the effort to develop a fully integrated view of the body, with all parts connected and fully interacting in a realistic way. This paper will present the status of current (2000) plans by the National Space Biomedical Research Institute to initiate research in this area of integrative physiology and medicine. Specifically, three example projects are discussed as potential stepping stones towards the ultimate goal of producing a digital human. These projects relate to developing a functional model of the human musculoskeletal system and the heart. c2002 COSPAR. Published by Elsevier Science Ltd. All rights reserved.

Developing a clinical translational neuroscience taxonomy for anxiety and mood disorder: protocol for the baseline-follow up Research domain criteria Anxiety and Depression ("RAD") project.

PubMed

Williams, Leanne M; Goldstein-Piekarski, Andrea N; Chowdhry, Nowreen; Grisanzio, Katherine A; Haug, Nancy A; Samara, Zoe; Etkin, Amit; O'Hara, Ruth; Schatzberg, Alan F; Suppes, Trisha; Yesavage, Jerome

2016-03-15

Understanding how brain circuit dysfunctions relate to specific symptoms offers promise for developing a brain-based taxonomy for classifying psychopathology, identifying targets for mechanistic studies and ultimately for guiding treatment choice. The goal of the Research Domain Criteria (RDoC) initiative of the National Institute of Mental Health is to accelerate the development of such neurobiological models of mental disorder independent of traditional diagnostic criteria. In our RDoC Anxiety and Depression ("RAD") project we focus trans-diagnostically on the spectrum of depression and anxiety psychopathology. Our aims are a) to use brain imaging to define cohesive dimensions defined by dysfunction of circuits involved in reactivity to and regulation of negatively valenced emotional stimulation and in cognitive control, b) to assess the relationships between these dimension and specific symptoms, behavioral performance and the real world capacity to function socially and at work and c) to assess the stability of brain-symptom-behavior-function relationships over time. Here we present the protocol for the "RAD" project, one of the first RDoC studies to use brain circuit functioning to define new dimensions of psychopathology. The RAD project follows baseline-follow up design. In line with RDoC principles we use a strategy for recruiting all clients who "walk through the door" of a large community mental health clinic as well as the surrounding community. The clinic attends to a broad spectrum of anxiety and mood-related symptoms. Participants are unmedicated and studied at baseline using a standardized battery of functional brain imaging, structural brain imaging and behavioral probes that assay constructs of threat reactivity, threat regulation and cognitive control. The battery also includes self-report measures of anxiety and mood symptoms, and social and occupational functioning. After baseline assessments, therapists in the clinic apply treatment planning as usual. Follow-up assessments are undertaken at 3 months, to establish the reliability of brain-based subgroups over time and to assess whether these subgroups predict real-world functional capacity over time. First enrollment was August 2013, and is ongoing. This project is designed to advance knowledge toward a neural circuit taxonomy for mental disorder. Data will be shared via the RDoC database for dissemination to the scientific community. The clinical translational neuroscience goals of the project are to develop brain-behavior profile reports for each individual participant and to refine these reports with therapist feedback. Reporting of results is expected from December 2016 onward. ClinicalTrials.gov Identifier: NCT02220309 . Registered: August 13, 2014.

On Expression Patterns and Developmental Origin of Human Brain Regions.

PubMed

Kirsch, Lior; Chechik, Gal

2016-08-01

Anatomical substructures of the human brain have characteristic cell-types, connectivity and local circuitry, which are reflected in area-specific transcriptome signatures, but the principles governing area-specific transcription and their relation to brain development are still being studied. In adult rodents, areal transcriptome patterns agree with the embryonic origin of brain regions, but the processes and genes that preserve an embryonic signature in regional expression profiles were not quantified. Furthermore, it is not clear how embryonic-origin signatures of adult-brain expression interplay with changes in expression patterns during development. Here we first quantify which genes have regional expression-patterns related to the developmental origin of brain regions, using genome-wide mRNA expression from post-mortem adult human brains. We find that almost all human genes (92%) exhibit an expression pattern that agrees with developmental brain-region ontology, but that this agreement changes at multiple phases during development. Agreement is particularly strong in neuron-specific genes, but also in genes that are not spatially correlated with neuron-specific or glia-specific markers. Surprisingly, agreement is also stronger in early-evolved genes. We further find that pairs of similar genes having high agreement to developmental region ontology tend to be more strongly correlated or anti-correlated, and that the strength of spatial correlation changes more strongly in gene pairs with stronger embryonic signatures. These results suggest that transcription regulation of most genes in the adult human brain is spatially tuned in a way that changes through life, but in agreement with development-determined brain regions.

The human parental brain: In vivo neuroimaging

PubMed Central

Swain, James E.

2015-01-01

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

On Expression Patterns and Developmental Origin of Human Brain Regions

PubMed Central

Kirsch, Lior; Chechik, Gal

2016-01-01

Anatomical substructures of the human brain have characteristic cell-types, connectivity and local circuitry, which are reflected in area-specific transcriptome signatures, but the principles governing area-specific transcription and their relation to brain development are still being studied. In adult rodents, areal transcriptome patterns agree with the embryonic origin of brain regions, but the processes and genes that preserve an embryonic signature in regional expression profiles were not quantified. Furthermore, it is not clear how embryonic-origin signatures of adult-brain expression interplay with changes in expression patterns during development. Here we first quantify which genes have regional expression-patterns related to the developmental origin of brain regions, using genome-wide mRNA expression from post-mortem adult human brains. We find that almost all human genes (92%) exhibit an expression pattern that agrees with developmental brain-region ontology, but that this agreement changes at multiple phases during development. Agreement is particularly strong in neuron-specific genes, but also in genes that are not spatially correlated with neuron-specific or glia-specific markers. Surprisingly, agreement is also stronger in early-evolved genes. We further find that pairs of similar genes having high agreement to developmental region ontology tend to be more strongly correlated or anti-correlated, and that the strength of spatial correlation changes more strongly in gene pairs with stronger embryonic signatures. These results suggest that transcription regulation of most genes in the adult human brain is spatially tuned in a way that changes through life, but in agreement with development-determined brain regions. PMID:27564987

Long-Term Stability of Motor Cortical Activity: Implications for Brain Machine Interfaces and Optimal Feedback Control.

PubMed

Flint, Robert D; Scheid, Michael R; Wright, Zachary A; Solla, Sara A; Slutzky, Marc W

2016-03-23

The human motor system is capable of remarkably precise control of movements--consider the skill of professional baseball pitchers or surgeons. This precise control relies upon stable representations of movements in the brain. Here, we investigated the stability of cortical activity at multiple spatial and temporal scales by recording local field potentials (LFPs) and action potentials (multiunit spikes, MSPs) while two monkeys controlled a cursor either with their hand or directly from the brain using a brain-machine interface. LFPs and some MSPs were remarkably stable over time periods ranging from 3 d to over 3 years; overall, LFPs were significantly more stable than spikes. We then assessed whether the stability of all neural activity, or just a subset of activity, was necessary to achieve stable behavior. We showed that projections of neural activity into the subspace relevant to the task (the "task-relevant space") were significantly more stable than were projections into the task-irrelevant (or "task-null") space. This provides cortical evidence in support of the minimum intervention principle, which proposes that optimal feedback control (OFC) allows the brain to tightly control only activity in the task-relevant space while allowing activity in the task-irrelevant space to vary substantially from trial to trial. We found that the brain appears capable of maintaining stable movement representations for extremely long periods of time, particularly so for neural activity in the task-relevant space, which agrees with OFC predictions. It is unknown whether cortical signals are stable for more than a few weeks. Here, we demonstrate that motor cortical signals can exhibit high stability over several years. This result is particularly important to brain-machine interfaces because it could enable stable performance with infrequent recalibration. Although we can maintain movement accuracy over time, movement components that are unrelated to the goals of a task (such as elbow position during reaching) often vary from trial to trial. This is consistent with the minimum intervention principle of optimal feedback control. We provide evidence that the motor cortex acts according to this principle: cortical activity is more stable in the task-relevant space and more variable in the task-irrelevant space. Copyright © 2016 the authors 0270-6474/16/363623-10$15.00/0.

Anatomical connectivity influences both intra- and inter-brain synchronizations.

PubMed

Dumas, Guillaume; Chavez, Mario; Nadel, Jacqueline; Martinerie, Jacques

2012-01-01

Recent development in diffusion spectrum brain imaging combined to functional simulation has the potential to further our understanding of how structure and dynamics are intertwined in the human brain. At the intra-individual scale, neurocomputational models have already started to uncover how the human connectome constrains the coordination of brain activity across distributed brain regions. In parallel, at the inter-individual scale, nascent social neuroscience provides a new dynamical vista of the coupling between two embodied cognitive agents. Using EEG hyperscanning to record simultaneously the brain activities of subjects during their ongoing interaction, we have previously demonstrated that behavioral synchrony correlates with the emergence of inter-brain synchronization. However, the functional meaning of such synchronization remains to be specified. Here, we use a biophysical model to quantify to what extent inter-brain synchronizations are related to the anatomical and functional similarity of the two brains in interaction. Pairs of interacting brains were numerically simulated and compared to real data. Results show a potential dynamical property of the human connectome to facilitate inter-individual synchronizations and thus may partly account for our propensity to generate dynamical couplings with others.

Emotional arousal and multiple memory systems in the mammalian brain

PubMed Central

Packard, Mark G.; Goodman, Jarid

2012-01-01

Emotional arousal induced by stress and/or anxiety can exert complex effects on learning and memory processes in mammals. Recent studies have begun to link study of the influence of emotional arousal on memory with earlier research indicating that memory is organized in multiple systems in the brain that differ in terms of the “type” of memory they mediate. Specifically, these studies have examined whether emotional arousal may have a differential effect on the “cognitive” and stimulus-response “habit” memory processes sub-served by the hippocampus and dorsal striatum, respectively. Evidence indicates that stress or the peripheral injection of anxiogenic drugs can bias animals and humans toward the use of striatal-dependent habit memory in dual-solution tasks in which both hippocampal and striatal-based strategies can provide an adequate solution. A bias toward the use of habit memory can also be produced by intra-basolateral amygdala (BLA) administration of anxiogenic drugs, consistent with the well documented role of efferent projections of this brain region in mediating the modulatory influence of emotional arousal on memory. In some learning situations, the bias toward the use of habit memory produced by emotional arousal appears to result from an impairing effect on hippocampus-dependent cognitive memory. Further research examining the neural mechanisms linking emotion and the relative use of multiple memory systems should prove useful in view of the potential role for maladaptive habitual behaviors in various human psychopathologies. PMID:22470324

Nonequilibrium landscape theory of neural networks.

PubMed

Yan, Han; Zhao, Lei; Hu, Liang; Wang, Xidi; Wang, Erkang; Wang, Jin

2013-11-05

The brain map project aims to map out the neuron connections of the human brain. Even with all of the wirings mapped out, the global and physical understandings of the function and behavior are still challenging. Hopfield quantified the learning and memory process of symmetrically connected neural networks globally through equilibrium energy. The energy basins of attractions represent memories, and the memory retrieval dynamics is determined by the energy gradient. However, the realistic neural networks are asymmetrically connected, and oscillations cannot emerge from symmetric neural networks. Here, we developed a nonequilibrium landscape-flux theory for realistic asymmetrically connected neural networks. We uncovered the underlying potential landscape and the associated Lyapunov function for quantifying the global stability and function. We found the dynamics and oscillations in human brains responsible for cognitive processes and physiological rhythm regulations are determined not only by the landscape gradient but also by the flux. We found that the flux is closely related to the degrees of the asymmetric connections in neural networks and is the origin of the neural oscillations. The neural oscillation landscape shows a closed-ring attractor topology. The landscape gradient attracts the network down to the ring. The flux is responsible for coherent oscillations on the ring. We suggest the flux may provide the driving force for associations among memories. We applied our theory to rapid-eye movement sleep cycle. We identified the key regulation factors for function through global sensitivity analysis of landscape topography against wirings, which are in good agreements with experiments.

Nonequilibrium landscape theory of neural networks

PubMed Central

Yan, Han; Zhao, Lei; Hu, Liang; Wang, Xidi; Wang, Erkang; Wang, Jin

2013-01-01

The brain map project aims to map out the neuron connections of the human brain. Even with all of the wirings mapped out, the global and physical understandings of the function and behavior are still challenging. Hopfield quantified the learning and memory process of symmetrically connected neural networks globally through equilibrium energy. The energy basins of attractions represent memories, and the memory retrieval dynamics is determined by the energy gradient. However, the realistic neural networks are asymmetrically connected, and oscillations cannot emerge from symmetric neural networks. Here, we developed a nonequilibrium landscape–flux theory for realistic asymmetrically connected neural networks. We uncovered the underlying potential landscape and the associated Lyapunov function for quantifying the global stability and function. We found the dynamics and oscillations in human brains responsible for cognitive processes and physiological rhythm regulations are determined not only by the landscape gradient but also by the flux. We found that the flux is closely related to the degrees of the asymmetric connections in neural networks and is the origin of the neural oscillations. The neural oscillation landscape shows a closed-ring attractor topology. The landscape gradient attracts the network down to the ring. The flux is responsible for coherent oscillations on the ring. We suggest the flux may provide the driving force for associations among memories. We applied our theory to rapid-eye movement sleep cycle. We identified the key regulation factors for function through global sensitivity analysis of landscape topography against wirings, which are in good agreements with experiments. PMID:24145451

An Exploratory Study of the Possible Impact of Cerebral Hemisphericity on the Performance of Select Linear, Non-Linear, and Spatial Computer Tasks.

ERIC Educational Resources Information Center

McCluskey, James J.

1997-01-01

A study of 160 undergraduate journalism students trained to design projects (stacks) using HyperCard on Macintosh computers determined that right-brain dominant subjects outperformed left-brain and mixed-brain dominant subjects, whereas left-brain dominant subjects out performed mixed-brain dominant subjects in several areas. Recommends future…

BNCI systems as a potential assistive technology: ethical issues and participatory research in the BrainAble project.

PubMed

Carmichael, Clare; Carmichael, Patrick

2014-01-01

This paper highlights aspects related to current research and thinking about ethical issues in relation to Brain Computer Interface (BCI) and Brain-Neuronal Computer Interfaces (BNCI) research through the experience of one particular project, BrainAble, which is exploring and developing the potential of these technologies to enable people with complex disabilities to control computers. It describes how ethical practice has been developed both within the multidisciplinary research team and with participants. The paper presents findings in which participants shared their views of the project prototypes, of the potential of BCI/BNCI systems as an assistive technology, and of their other possible applications. This draws attention to the importance of ethical practice in projects where high expectations of technologies, and representations of "ideal types" of disabled users may reinforce stereotypes or drown out participant "voices". Ethical frameworks for research and development in emergent areas such as BCI/BNCI systems should be based on broad notions of a "duty of care" while being sufficiently flexible that researchers can adapt project procedures according to participant needs. They need to be frequently revisited, not only in the light of experience, but also to ensure they reflect new research findings and ever more complex and powerful technologies.

The evolution of modern human brain shape

PubMed Central

Neubauer, Simon; Hublin, Jean-Jacques; Gunz, Philipp

2018-01-01

Modern humans have large and globular brains that distinguish them from their extinct Homo relatives. The characteristic globularity develops during a prenatal and early postnatal period of rapid brain growth critical for neural wiring and cognitive development. However, it remains unknown when and how brain globularity evolved and how it relates to evolutionary brain size increase. On the basis of computed tomographic scans and geometric morphometric analyses, we analyzed endocranial casts of Homo sapiens fossils (N = 20) from different time periods. Our data show that, 300,000 years ago, brain size in early H. sapiens already fell within the range of present-day humans. Brain shape, however, evolved gradually within the H. sapiens lineage, reaching present-day human variation between about 100,000 and 35,000 years ago. This process started only after other key features of craniofacial morphology appeared modern and paralleled the emergence of behavioral modernity as seen from the archeological record. Our findings are consistent with important genetic changes affecting early brain development within the H. sapiens lineage since the origin of the species and before the transition to the Later Stone Age and the Upper Paleolithic that mark full behavioral modernity. PMID:29376123

The evolution of modern human brain shape.

PubMed

Neubauer, Simon; Hublin, Jean-Jacques; Gunz, Philipp

2018-01-01

Modern humans have large and globular brains that distinguish them from their extinct Homo relatives. The characteristic globularity develops during a prenatal and early postnatal period of rapid brain growth critical for neural wiring and cognitive development. However, it remains unknown when and how brain globularity evolved and how it relates to evolutionary brain size increase. On the basis of computed tomographic scans and geometric morphometric analyses, we analyzed endocranial casts of Homo sapiens fossils ( N = 20) from different time periods. Our data show that, 300,000 years ago, brain size in early H. sapiens already fell within the range of present-day humans. Brain shape, however, evolved gradually within the H. sapiens lineage, reaching present-day human variation between about 100,000 and 35,000 years ago. This process started only after other key features of craniofacial morphology appeared modern and paralleled the emergence of behavioral modernity as seen from the archeological record. Our findings are consistent with important genetic changes affecting early brain development within the H. sapiens lineage since the origin of the species and before the transition to the Later Stone Age and the Upper Paleolithic that mark full behavioral modernity.

Striking differences in glucose and lactate levels between brain extracellular fluid and plasma in conscious human subjects: effects of hyperglycemia and hypoglycemia.

PubMed

Abi-Saab, Walid M; Maggs, David G; Jones, Tim; Jacob, Ralph; Srihari, Vinod; Thompson, James; Kerr, David; Leone, Paola; Krystal, John H; Spencer, Dennis D; During, Matthew J; Sherwin, Robert S

2002-03-01

Brain levels of glucose and lactate in the extracellular fluid (ECF), which reflects the environment to which neurons are exposed, have never been studied in humans under conditions of varying glycemia. The authors used intracerebral microdialysis in conscious human subjects undergoing electrophysiologic evaluation for medically intractable epilepsy and measured ECF levels of glucose and lactate under basal conditions and during a hyperglycemia-hypoglycemia clamp study. Only measurements from nonepileptogenic areas were included. Under basal conditions, the authors found the metabolic milieu in the brain to be strikingly different from that in the circulation. In contrast to plasma, lactate levels in brain ECF were threefold higher than glucose. Results from complementary studies in rats were consistent with the human data. During the hyperglycemia-hypoglycemia clamp study the relationship between plasma and brain ECF levels of glucose remained similar, but changes in brain ECF glucose lagged approximately 30 minutes behind changes in plasma. The data demonstrate that the brain is exposed to substantially lower levels of glucose and higher levels of lactate than those in plasma; moreover, the brain appears to be a site of significant anaerobic glycolysis, raising the possibility that glucose-derived lactate is an important fuel for the brain.

"Adotta scienza e arte nella tua classe": The results of a successfully teaching project which combines science with art⋆

NASA Astrophysics Data System (ADS)

Giansanti, S.

2015-03-01

The project called Adotta scienza e arte nella tua classe ("Adopt Science and Art in your class"), on the interconnection between science and art, has been addressed to the Italian secondary middle and high school involving more than 200 teachers and about 2200 students. The main purpose of this project is to make the young students aware of the strong link between science and art is a unique cultural and interdisciplinary occasion. To reach this goal, the Adotta project asked students to produce an artwork inspired by the interpretation of a quotation among a hundred commented quotes by physicists, mathematicians, scientist, writers, artists, accompanied by an original short sentence written by students themselves. More than 1000 artworks have been produced and collected in two galleries on Facebook. From their analysis emerges the students' feeling about science, which is usually associated to human brain, based on mathematical laws and related to technological progress, but it is also a powerful tool that should be responsibly used. This project also valorizes teachers' role in scientific education through activities that encourage students to recognize science in every aspect of their lives.

High-throughput RNA sequencing reveals structural differences of orthologous brain-expressed genes between western lowland gorillas and humans.

PubMed

Lipovich, Leonard; Hou, Zhuo-Cheng; Jia, Hui; Sinkler, Christopher; McGowen, Michael; Sterner, Kirstin N; Weckle, Amy; Sugalski, Amara B; Pipes, Lenore; Gatti, Domenico L; Mason, Christopher E; Sherwood, Chet C; Hof, Patrick R; Kuzawa, Christopher W; Grossman, Lawrence I; Goodman, Morris; Wildman, Derek E

2016-02-01

The human brain and human cognitive abilities are strikingly different from those of other great apes despite relatively modest genome sequence divergence. However, little is presently known about the interspecies divergence in gene structure and transcription that might contribute to these phenotypic differences. To date, most comparative studies of gene structure in the brain have examined humans, chimpanzees, and macaque monkeys. To add to this body of knowledge, we analyze here the brain transcriptome of the western lowland gorilla (Gorilla gorilla gorilla), an African great ape species that is phylogenetically closely related to humans, but with a brain that is approximately one-third the size. Manual transcriptome curation from a sample of the planum temporale region of the neocortex revealed 12 protein-coding genes and one noncoding-RNA gene with exons in the gorilla unmatched by public transcriptome data from the orthologous human loci. These interspecies gene structure differences accounted for a total of 134 amino acids in proteins found in the gorilla that were absent from protein products of the orthologous human genes. Proteins varying in structure between human and gorilla were involved in immunity and energy metabolism, suggesting their relevance to phenotypic differences. This gorilla neocortical transcriptome comprises an empirical, not homology- or prediction-driven, resource for orthologous gene comparisons between human and gorilla. These findings provide a unique repository of the sequences and structures of thousands of genes transcribed in the gorilla brain, pointing to candidate genes that may contribute to the traits distinguishing humans from other closely related great apes. © 2015 Wiley Periodicals, Inc.

A probabilistic atlas of human brainstem pathways based on connectome imaging data.

PubMed

Tang, Yuchun; Sun, Wei; Toga, Arthur W; Ringman, John M; Shi, Yonggang

2018-04-01

The brainstem is a critical structure that regulates vital autonomic functions, houses the cranial nerves and their nuclei, relays motor and sensory information between the brain and spinal cord, and modulates cognition, mood, and emotions. As a primary relay center, the fiber pathways of the brainstem include efferent and afferent connections among the cerebral cortex, spinal cord, and cerebellum. While diffusion MRI has been successfully applied to map various brain pathways, its application for the in vivo imaging of the brainstem pathways has been limited due to inadequate resolution and large susceptibility-induced distortion artifacts. With the release of high-resolution data from the Human Connectome Project (HCP), there is increasing interest in mapping human brainstem pathways. Previous works relying on HCP data to study brainstem pathways, however, did not consider the prevalence (>80%) of large distortions in the brainstem even after the application of correction procedures from the HCP-Pipeline. They were also limited in the lack of adequate consideration of subject variability in either fiber pathways or region of interests (ROIs) used for bundle reconstruction. To overcome these limitations, we develop in this work a probabilistic atlas of 23 major brainstem bundles using high-quality HCP data passing rigorous quality control. For the large-scale data from the 500-Subject release of HCP, we conducted extensive quality controls to exclude subjects with severe distortions in the brainstem area. After that, we developed a systematic protocol to manually delineate 1300 ROIs on 20 HCP subjects (10 males; 10 females) for the reconstruction of fiber bundles using tractography techniques. Finally, we leveraged our novel connectome modeling techniques including high order fiber orientation distribution (FOD) reconstruction from multi-shell diffusion imaging and topography-preserving tract filtering algorithms to successfully reconstruct the 23 fiber bundles for each subject, which were then used to calculate the probabilistic atlases in the MNI152 space for public release. In our experimental results, we demonstrate that our method yielded anatomically faithful reconstruction of the brainstem pathways and achieved improved performance in comparison with an existing atlas of cerebellar peduncles based on HCP data. These atlases have been publicly released on NITRIC (https://www.nitrc.org/projects/brainstem_atlas/) and can be readily used by brain imaging researchers interested in studying brainstem pathways. Copyright © 2017 Elsevier Inc. All rights reserved.

Gene expression changes in rat brain after short and long exposures to particulate matter in Los Angeles basin air: Comparison with human brain tumors.

PubMed

Ljubimova, Julia Y; Kleinman, Michael T; Karabalin, Natalya M; Inoue, Satoshi; Konda, Bindu; Gangalum, Pallavi; Markman, Janet L; Ljubimov, Alexander V; Black, Keith L

2013-11-01

Air pollution negatively impacts pulmonary, cardiovascular, and central nervous systems. Although its influence on brain cancer is unclear, toxic pollutants can cause blood-brain barrier disruption, enabling them to reach the brain and cause alterations leading to tumor development. By gene microarray analysis validated by quantitative RT-PCR and immunostaining we examined whether rat (n=104) inhalation exposure to air pollution particulate matter (PM) resulted in brain molecular changes similar to those associated with human brain tumors. Global brain gene expression was analyzed after exposure to PM (coarse, 2.5-10μm; fine, <2.5μm; or ultrafine, <0.15μm) and purified air for different times, short (0.5, 1, and 3 months) and chronic (10 months), for 5h per day, four days per week. Expression of select gene products was also studied in human brain (n=7) and in tumors (n=83). Arc/Arg3.1 and Rac1 genes, and their protein products were selected for further examination. Arc was elevated upon two-week to three-month exposure to coarse PM and declined after 10-month exposure. Rac1 was significantly elevated upon 10-month coarse PM exposure. On human brain tumor sections, Arc was expressed in benign meningiomas and low-grade gliomas but was much lower in high-grade tumors. Conversely, Rac1 was elevated in high-grade vs. low-grade gliomas. Arc is thus associated with early brain changes and low-grade tumors, whereas Rac1 is associated with long-term PM exposure and highly aggressive tumors. In summary, exposure to air PM leads to distinct changes in rodent brain gene expression similar to those observed in human brain tumors. Copyright © 2013 Elsevier GmbH. All rights reserved.

Can a few non‐coding mutations make a human brain?

PubMed Central

Franchini, Lucía F.

2015-01-01

The recent finding that the human version of a neurodevelopmental enhancer of the Wnt receptor Frizzled 8 (FZD8) gene alters neural progenitor cell cycle timing and brain size is a step forward to understanding human brain evolution. The human brain is distinctive in terms of its cognitive abilities as well as its susceptibility to neurological disease. Identifying which of the millions of genomic changes that occurred during human evolution led to these and other uniquely human traits is extremely challenging. Recent studies have demonstrated that many of the fastest evolving regions of the human genome function as gene regulatory enhancers during embryonic development and that the human‐specific mutations in them might alter expression patterns. However, elucidating molecular and cellular effects of sequence or expression pattern changes is a major obstacle to discovering the genetic bases of the evolution of our species. There is much work to do before human‐specific genetic and genomic changes are linked to complex human traits. Also watch the Video Abstract. PMID:26350501

Fifth dimension of life and the 4/5 allometric scaling law for human brain.

PubMed

He, Ji-Huan; Zhang, Juan

2004-01-01

Brain cells are not spherical. The basal metabolic rate (B) of a spherical cell scales as B approximately r2, where r is the radius of the cell; that of a brain cell scales as B approximately r(d), where r is the characteristic radius of the cell and d is the fractal dimensionality of its contour. The fractal geometry of the cell leads to a 4/5 allometric scaling law for human brain, uniquely endowing humans with a 5th dimension and successfully explains why the scaling exponent varies during rest and exercise. A striking analogy between Kleiber's 3/4 law and Newton's second law is heuristically illustrated. A physical explanation is given for the 4th dimension of life for three-dimensional organisms and the 5th dimension for human brain.

How to Direct the Edges of the Connectomes: Dynamics of the Consensus Connectomes and the Development of the Connections in the Human Brain.

PubMed

Kerepesi, Csaba; Szalkai, Balázs; Varga, Bálint; Grolmusz, Vince

2016-01-01

The human braingraph or the connectome is the object of an intensive research today. The advantage of the graph-approach to brain science is that the rich structures, algorithms and definitions of graph theory can be applied to the anatomical networks of the connections of the human brain. In these graphs, the vertices correspond to the small (1-1.5 cm2) areas of the gray matter, and two vertices are connected by an edge, if a diffusion-MRI based workflow finds fibers of axons, running between those small gray matter areas in the white matter of the brain. One main question of the field today is discovering the directions of the connections between the small gray matter areas. In a previous work we have reported the construction of the Budapest Reference Connectome Server http://connectome.pitgroup.org from the data recorded in the Human Connectome Project of the NIH. The server generates the consensus braingraph of 96 subjects in Version 2, and of 418 subjects in Version 3, according to selectable parameters. After the Budapest Reference Connectome Server had been published, we recognized a surprising and unforeseen property of the server. The server can generate the braingraph of connections that are present in at least k graphs out of the 418, for any value of k = 1, 2, …, 418. When the value of k is changed from k = 418 through 1 by moving a slider at the webserver from right to left, certainly more and more edges appear in the consensus graph. The astonishing observation is that the appearance of the new edges is not random: it is similar to a growing shrub. We refer to this phenomenon as the Consensus Connectome Dynamics. We hypothesize that this movement of the slider in the webserver may copy the development of the connections in the human brain in the following sense: the connections that are present in all subjects are the oldest ones, and those that are present only in a decreasing fraction of the subjects are gradually the newer connections in the individual brain development. An animation on the phenomenon is available at https://youtu.be/yxlyudPaVUE. Based on this observation and the related hypothesis, we can assign directions to some of the edges of the connectome as follows: Let Gk + 1 denote the consensus connectome where each edge is present in at least k+1 graphs, and let Gk denote the consensus connectome where each edge is present in at least k graphs. Suppose that vertex v is not connected to any other vertices in Gk+1, and becomes connected to a vertex u in Gk, where u was connected to other vertices already in Gk+1. Then we direct this (v, u) edge from v to u.

On data modeling for neurological application

NASA Astrophysics Data System (ADS)

Woźniak, Karol; Mulawka, Jan

The aim of this paper is to design and implement information system containing large database dedicated to support neurological-psychiatric examinations focused on human brain after stroke. This approach encompasses the following steps: analysis of software requirements, presentation of the problem solving concept, design and implementation of the final information system. Certain experiments were performed in order to verify the correctness of the project ideas. The approach can be considered as an interdisciplinary venture. Elaboration of the system architecture, data model and the tools supporting medical examinations are provided. The achievement of the design goals is demonstrated in the final conclusion.

Design and Application of a Circuit for Measuring Frequency and Duty Cycle of Stimulated Bioelectrical Signal

NASA Astrophysics Data System (ADS)

Tang, Li-Ming; Chang, Ben-Kang; Liu, Tie-Bing; Wu, Min; Ling, Gang

2002-12-01

To design a new type of circuit for measuring frequency & duty cycle of stimulated bioelectrical signal for the project of 'the map of neuron-threshold in human brain and its clinical application'. This circuit was designed according to the character of stimulated bioelectrical signals. It was tested and improved and then used in the neuron -threshold stimulator. The circuit was found to be very accurate for measuring frequency and the error for measuring duty cycle was below 0.2%. This circuit is well-designed, simple, easy to use, and can be applied in many systems.

[Introduction of neuroethics: out of clinic, beyond academia in human brain research].

PubMed

Fukushi, Tamami; Sakura, Osamu

2008-11-01

Higher cognitive function in human brain is one of well-developed fields of neuroscience research in the 21st century. Especially functional magnetic resonance imaging (fMRI) and near infrared recording system have brought so many non-clinical researchers whose background is such as cognitive psychology, economics, politics, pedagogy, and so on, to the human brain mapping study. Authors have introduced the ethical issues related to incidental findings during the fMRI recording for non-clinical purpose, which is a typical problem derived from such expanded human brain research under non clinical condition, that is, neuroethics. In the present article we would introduce neuroethical issues in contexts of "out of clinic" and "beyond academia".

In vivo Magnetic Resonance Spectroscopy of cerebral glycogen metabolism in animals and humans.

PubMed

Khowaja, Ameer; Choi, In-Young; Seaquist, Elizabeth R; Öz, Gülin

2015-02-01

Glycogen serves as an important energy reservoir in the human body. Despite the abundance of glycogen in the liver and skeletal muscles, its concentration in the brain is relatively low, hence its significance has been questioned. A major challenge in studying brain glycogen metabolism has been the lack of availability of non-invasive techniques for quantification of brain glycogen in vivo. Invasive methods for brain glycogen quantification such as post mortem extraction following high energy microwave irradiation are not applicable in the human brain. With the advent of (13)C Magnetic Resonance Spectroscopy (MRS), it has been possible to measure brain glycogen concentrations and turnover in physiological conditions, as well as under the influence of stressors such as hypoglycemia and visual stimulation. This review presents an overview of the principles of the (13)C MRS methodology and its applications in both animals and humans to further our understanding of glycogen metabolism under normal physiological and pathophysiological conditions such as hypoglycemia unawareness.

In vivo Magnetic Resonance Spectroscopy of cerebral glycogen metabolism in animals and humans

PubMed Central

Khowaja, Ameer; Choi, In-Young; Seaquist, Elizabeth R.; Öz, Gülin

2015-01-01

Glycogen serves as an important energy reservoir in the human body. Despite the abundance of glycogen in the liver and skeletal muscles, its concentration in the brain is relatively low, hence its significance has been questioned. A major challenge in studying brain glycogen metabolism has been the lack of availability of non-invasive techniques for quantification of brain glycogen in vivo. Invasive methods for brain glycogen quantification such as post mortem extraction following high energy microwave irradiation are not applicable in the human brain. With the advent of 13C Magnetic Resonance Spectroscopy (MRS), it has been possible to measure brain glycogen concentrations and turnover in physiological conditions, as well as under the influence of stressors such as hypoglycemia and visual stimulation. This review presents an overview of the principles of the 13C MRS methodology and its applications in both animals and humans to further our understanding of glycogen metabolism under normal physiological and pathophysiological conditions such as hypoglycemia unawareness. PMID:24676563

MRI with intrathecal MRI gadolinium contrast medium administration: a possible method to assess glymphatic function in human brain

PubMed Central

Ringstad, Geir

2015-01-01

Recently, the “glymphatic system” of the brain has been discovered in rodents, which is a paravascular, transparenchymal route for clearance of excess brain metabolites and distribution of compounds in the cerebrospinal fluid. It has already been demonstrated that intrathecally administered gadolinium (Gd) contrast medium distributes along this route in rats, but so far not in humans. A 27-year-old woman underwent magnetic resonance imaging (MRI) with intrathecal administration of gadobutrol, which distributed throughout her entire brain after 1 and 4.5 h. MRI with intrathecal Gd may become a tool to study glymphatic function in the human brain. PMID:26634147

Fluorescent-Protein Stabilization and High-Resolution Imaging of Cleared, Intact Mouse Brains

PubMed Central

Schwarz, Martin K.; Scherbarth, Annemarie; Sprengel, Rolf; Engelhardt, Johann; Theer, Patrick; Giese, Guenter

2015-01-01

In order to observe and quantify long-range neuronal connections in intact mouse brain by light microscopy, it is first necessary to clear the brain, thus suppressing refractive-index variations. Here we describe a method that clears the brain and preserves the signal from proteinaceous fluorophores using a pH-adjusted non-aqueous index-matching medium. Successful clearing is enabled through the use of either 1-propanol or tert-butanol during dehydration whilst maintaining a basic pH. We show that high-resolution fluorescence imaging of entire, structurally intact juvenile and adult mouse brains is possible at subcellular resolution, even following many months in clearing solution. We also show that axonal long-range projections that are EGFP-labelled by modified Rabies virus can be imaged throughout the brain using a purpose-built light-sheet fluorescence microscope. To demonstrate the viability of the technique, we determined a detailed map of the monosynaptic projections onto a target cell population in the lateral entorhinal cortex. This example demonstrates that our method permits the quantification of whole-brain connectivity patterns at the subcellular level in the uncut brain. PMID:25993380

In vivo1H NMR spectroscopy of the human brain at 9.4 T: Initial results

NASA Astrophysics Data System (ADS)

Deelchand, Dinesh Kumar; Moortele, Pierre-François Van de; Adriany, Gregor; Iltis, Isabelle; Andersen, Peter; Strupp, John P.; Thomas Vaughan, J.; Uğurbil, Kâmil; Henry, Pierre-Gilles

2010-09-01

In vivo proton NMR spectroscopy allows non-invasive detection and quantification of a wide range of biochemical compounds in the brain. Higher field strength is generally considered advantageous for spectroscopy due to increased signal-to-noise and increased spectral dispersion. So far 1H NMR spectra have been reported in the human brain up to 7 T. In this study we show that excellent quality short echo time STEAM and LASER 1H NMR spectra can be measured in the human brain at 9.4 T. The information content of the human brain spectra appears very similar to that measured in the past decade in rodent brains at the same field strength, in spite of broader linewidth in human brain. Compared to lower fields, the T1 relaxation times of metabolites were slightly longer while T2 relaxation values of metabolites were shorter (<100 ms) at 9.4 T. The linewidth of the total creatine (tCr) resonance at 3.03 ppm increased linearly with magnetic field (1.35 Hz/T from 1.5 T to 9.4 T), with a minimum achievable tCr linewidth of around 12.5 Hz at 9.4 T. At very high field, B0 microsusceptibility effects are the main contributor to the minimum achievable linewidth.

Development of Human Brain Structural Networks Through Infancy and Childhood

PubMed Central

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

2015-01-01

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

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

PubMed

Cecchelli, Romeo; Aday, Sezin; Sevin, Emmanuel; Almeida, Catarina; Culot, Maxime; Dehouck, Lucie; Coisne, Caroline; Engelhardt, Britta; Dehouck, Marie-Pierre; Ferreira, Lino

2014-01-01

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

Impact of high iron intake on cognition and neurodegeneration in humans and in animal models: a systematic review

PubMed Central

Agrawal, Sonal; Berggren, Kiersten L.; Marks, Eileen; Fox, Jonathan H.

2017-01-01

Abstract Context Accumulation of brain iron is linked to aging and protein-misfolding neurodegenerative diseases. High iron intake may influence important brain health outcomes in later life. Objective The aim of this systematic review was to examine evidence from animal and human studies of the effects of high iron intake or peripheral iron status on adult cognition, brain aging, and neurodegeneration. Data Sources MEDLINE, Scopus, CAB Abstracts, the Cochrane Central Register of Clinical Trials, and OpenGrey databases were searched. Study Selection Studies investigating the effect of elevated iron intake at all postnatal life stages in mammalian models and humans on measures of adult brain health were included. Data Extraction Data were extracted and evaluated by two authors independently, with discrepancies resolved by discussion. Neurodegenerative disease diagnosis and/or behavioral/cognitive, biochemical, and brain morphologic findings were used to study the effects of iron intake or peripheral iron status on brain health. Risk of bias was assessed for animal and human studies. PRISMA guidelines for reporting systematic reviews were followed. Results Thirty-four preclinical and 14 clinical studies were identified from database searches. Thirty-three preclinical studies provided evidence supporting an adverse effect of nutritionally relevant high iron intake in neonates on brain-health-related outcomes in adults. Human studies varied considerably in design, quality, and findings; none investigated the effects of high iron intake in neonates/infants. Conclusions Human studies are needed to verify whether dietary iron intake levels used in neonates/infants to prevent iron deficiency have effects on brain aging and neurodegenerative disease outcomes. PMID:28505363

Information flow between interacting human brains: Identification, validation, and relationship to social expertise

PubMed Central

Bilek, Edda; Ruf, Matthias; Schäfer, Axel; Akdeniz, Ceren; Calhoun, Vince D.; Schmahl, Christian; Demanuele, Charmaine; Tost, Heike; Kirsch, Peter; Meyer-Lindenberg, Andreas

2015-01-01

Social interactions are fundamental for human behavior, but the quantification of their neural underpinnings remains challenging. Here, we used hyperscanning functional MRI (fMRI) to study information flow between brains of human dyads during real-time social interaction in a joint attention paradigm. In a hardware setup enabling immersive audiovisual interaction of subjects in linked fMRI scanners, we characterize cross-brain connectivity components that are unique to interacting individuals, identifying information flow between the sender’s and receiver’s temporoparietal junction. We replicate these findings in an independent sample and validate our methods by demonstrating that cross-brain connectivity relates to a key real-world measure of social behavior. Together, our findings support a central role of human-specific cortical areas in the brain dynamics of dyadic interactions and provide an approach for the noninvasive examination of the neural basis of healthy and disturbed human social behavior with minimal a priori assumptions. PMID:25848050

Default mode network, motor network, dorsal and ventral basal ganglia networks in the rat brain: comparison to human networks using resting state-fMRI.

PubMed

Sierakowiak, Adam; Monnot, Cyril; Aski, Sahar Nikkhou; Uppman, Martin; Li, Tie-Qiang; Damberg, Peter; Brené, Stefan

2015-01-01

Rodent models are developed to enhance understanding of the underlying biology of different brain disorders. However, before interpreting findings from animal models in a translational aspect to understand human disease, a fundamental step is to first have knowledge of similarities and differences of the biological systems studied. In this study, we analyzed and verified four known networks termed: default mode network, motor network, dorsal basal ganglia network, and ventral basal ganglia network using resting state functional MRI (rsfMRI) in humans and rats. Our work supports the notion that humans and rats have common robust resting state brain networks and that rsfMRI can be used as a translational tool when validating animal models of brain disorders. In the future, rsfMRI may be used, in addition to short-term interventions, to characterize longitudinal effects on functional brain networks after long-term intervention in humans and rats.

Default Mode Network, Motor Network, Dorsal and Ventral Basal Ganglia Networks in the Rat Brain: Comparison to Human Networks Using Resting State-fMRI

PubMed Central

Sierakowiak, Adam; Monnot, Cyril; Aski, Sahar Nikkhou; Uppman, Martin; Li, Tie-Qiang; Damberg, Peter; Brené, Stefan

2015-01-01

Rodent models are developed to enhance understanding of the underlying biology of different brain disorders. However, before interpreting findings from animal models in a translational aspect to understand human disease, a fundamental step is to first have knowledge of similarities and differences of the biological systems studied. In this study, we analyzed and verified four known networks termed: default mode network, motor network, dorsal basal ganglia network, and ventral basal ganglia network using resting state functional MRI (rsfMRI) in humans and rats. Our work supports the notion that humans and rats have common robust resting state brain networks and that rsfMRI can be used as a translational tool when validating animal models of brain disorders. In the future, rsfMRI may be used, in addition to short-term interventions, to characterize longitudinal effects on functional brain networks after long-term intervention in humans and rats. PMID:25789862

DUF1220 protein domains drive proliferation in human neural stem cells and are associated with increased cortical volume in anthropoid primates.

PubMed

Keeney, J G; Davis, J M; Siegenthaler, J; Post, M D; Nielsen, B S; Hopkins, W D; Sikela, J M

2015-09-01

Genome sequences encoding DUF1220 protein domains show a burst in copy number among anthropoid species and especially humans, where they have undergone the greatest human lineage-specific copy number expansion of any protein coding sequence in the genome. While DUF1220 copy number shows a dosage-related association with brain size in both normal populations and in 1q21.1-associated microcephaly and macrocephaly, a function for these domains has not yet been described. Here we provide multiple lines of evidence supporting the view that DUF1220 domains function as drivers of neural stem cell proliferation among anthropoid species including humans. First, we show that brain MRI data from 131 individuals across 7 anthropoid species shows a strong correlation between DUF1220 copy number and multiple brain size-related measures. Using in situ hybridization analyses of human fetal brain, we also show that DUF1220 domains are expressed in the ventricular zone and primarily during human cortical neurogenesis, and are therefore expressed at the right time and place to be affecting cortical brain development. Finally, we demonstrate that in vitro expression of DUF1220 sequences in neural stem cells strongly promotes proliferation. Taken together, these data provide the strongest evidence so far reported implicating DUF1220 dosage in anthropoid and human brain expansion through mechanisms involving increasing neural stem cell proliferation.

Microglial Dynamics During Human Brain Development

PubMed Central

Menassa, David A.; Gomez-Nicola, Diego

2018-01-01

Microglial cells are thought to colonize the human cerebrum between the 4th and 24th gestational weeks. Rodent studies have demonstrated that these cells originate from yolk sac progenitors though it is not clear whether this directly pertains to human development. Our understanding of microglial cell dynamics in the developing human brain comes mostly from postmortem studies demonstrating that the beginning of microglial colonization precedes the appearance of the vasculature, the blood–brain barrier, astrogliogenesis, oligodendrogenesis, neurogenesis, migration, and myelination of the various brain areas. Furthermore, migrating microglial populations cluster by morphology and express differential markers within the developing brain and according to developmental age. With the advent of novel technologies such as RNA-sequencing in fresh human tissue, we are beginning to identify the molecular features of the adult microglial signature. However, this is may not extend to the much more dynamic and rapidly changing antenatal microglial population and this is further complicated by the scarcity of tissue resources. In this brief review, we first describe the various historic schools of thought that had debated the origin of microglial cells while examining the evidence supporting the various theories. We then proceed to examine the evidence we have accumulated on microglial dynamics in the developing human brain, present evidence from rodent studies on the functional role of microglia during development and finally identify limitations for the used approaches in human studies and highlight under investigated questions. PMID:29881376

Cognition in action: imaging brain/body dynamics in mobile humans.

PubMed

Gramann, Klaus; Gwin, Joseph T; Ferris, Daniel P; Oie, Kelvin; Jung, Tzyy-Ping; Lin, Chin-Teng; Liao, Lun-De; Makeig, Scott

2011-01-01

We have recently developed a mobile brain imaging method (MoBI), that allows for simultaneous recording of brain and body dynamics of humans actively behaving in and interacting with their environment. A mobile imaging approach was needed to study cognitive processes that are inherently based on the use of human physical structure to obtain behavioral goals. This review gives examples of the tight coupling between human physical structure with cognitive processing and the role of supraspinal activity during control of human stance and locomotion. Existing brain imaging methods for actively behaving participants are described and new sensor technology allowing for mobile recordings of different behavioral states in humans is introduced. Finally, we review recent work demonstrating the feasibility of a MoBI system that was developed at the Swartz Center for Computational Neuroscience at the University of California, San Diego, demonstrating the range of behavior that can be investigated with this method.

Effects of Sex Steroids in the Human Brain.

PubMed

Nguyen, Tuong-Vi; Ducharme, Simon; Karama, Sherif

2017-11-01

Sex steroids are thought to play a critical developmental role in shaping both cortical and subcortical structures in the human brain. Periods of profound changes in sex steroids invariably coincide with the onset of sex differences in mental health vulnerability, highlighting the importance of sex steroids in determining sexual differentiation of the brain. Yet, most of the evidence for the central effects of sex steroids relies on non-human studies, as several challenges have limited our understanding of these effects in humans: the lack of systematic assessment of the human sex steroid metabolome, the different developmental trajectories of specific sex steroids, the impact of genetic variation and epigenetic changes, and the plethora of interactions between sex steroids, sex chromosomes, neurotransmitters, and other hormonal systems. Here we review how multimodal strategies may be employed to bridge the gap between the basic and clinical understanding of sex steroid-related changes in the human brain.

High-resolution whole-brain diffusion MRI at 7T using radiofrequency parallel transmission.

PubMed

Wu, Xiaoping; Auerbach, Edward J; Vu, An T; Moeller, Steen; Lenglet, Christophe; Schmitter, Sebastian; Van de Moortele, Pierre-François; Yacoub, Essa; Uğurbil, Kâmil

2018-03-30

Investigating the utility of RF parallel transmission (pTx) for Human Connectome Project (HCP)-style whole-brain diffusion MRI (dMRI) data at 7 Tesla (7T). Healthy subjects were scanned in pTx and single-transmit (1Tx) modes. Multiband (MB), single-spoke pTx pulses were designed to image sagittal slices. HCP-style dMRI data (i.e., 1.05-mm resolutions, MB2, b-values = 1000/2000 s/mm 2 , 286 images and 40-min scan) and data with higher accelerations (MB3 and MB4) were acquired with pTx. pTx significantly improved flip-angle detected signal uniformity across the brain, yielding ∼19% increase in temporal SNR (tSNR) averaged over the brain relative to 1Tx. This allowed significantly enhanced estimation of multiple fiber orientations (with ∼21% decrease in dispersion) in HCP-style 7T dMRI datasets. Additionally, pTx pulses achieved substantially lower power deposition, permitting higher accelerations, enabling collection of the same data in 2/3 and 1/2 the scan time or of more data in the same scan time. pTx provides a solution to two major limitations for slice-accelerated high-resolution whole-brain dMRI at 7T; it improves flip-angle uniformity, and enables higher slice acceleration relative to current state-of-the-art. As such, pTx provides significant advantages for rapid acquisition of high-quality, high-resolution truly whole-brain dMRI data. © 2018 International Society for Magnetic Resonance in Medicine.

Default, Cognitive, and Affective Brain Networks in Human Tinnitus

DTIC Science & Technology

2015-10-01

AWARD NUMBER: W81XWH-13-1-0491 TITLE: Default, Cognitive, and Affective Brain Networks in Human Tinnitus PRINCIPAL INVESTIGATOR: Jennifer R...SUBTITLE 5a. CONTRACT NUMBER Default, Cognitive and Affective Brain Networks in Human Tinnitus 5b. GRANT NUMBER 5c. PROGRAM ELEMENT NUMBER 6...Release; Distribution Unlimited 13. SUPPLEMENTARY NOTES 14. ABSTRACT Tinnitus is a major health problem among those currently and formerly in military

Comparative Analysis of Human and Rodent Brain Primary Neuronal Culture Spontaneous Activity Using Micro-Electrode Array Technology.

PubMed

Napoli, Alessandro; Obeid, Iyad

2016-03-01

Electrical activity in embryonic brain tissue has typically been studied using Micro Electrode Array (MEA) technology to make dozens of simultaneous recordings from dissociated neuronal cultures, brain stem cell progenitors, or brain slices from fetal rodents. Although these rodent neuronal primary culture electrical properties are mostly investigated, it has not been yet established to what extent the electrical characteristics of rodent brain neuronal cultures can be generalized to those of humans. A direct comparison of spontaneous spiking activity between rodent and human primary neurons grown under the same in vitro conditions using MEA technology has never been carried out before and will be described in the present study. Human and rodent dissociated fetal brain neuronal cultures were established in-vitro by culturing on a glass grid of 60 planar microelectrodes neurons under identical conditions. Three different cultures of human neurons were produced from tissue sourced from a single aborted fetus (at 16-18 gestational weeks) and these were compared with seven different cultures of embryonic rat neurons (at 18 gestational days) originally isolated from a single rat. The results show that the human and rodent cultures behaved significantly differently. Whereas the rodent cultures demonstrated robust spontaneous activation and network activity after only 10 days, the human cultures required nearly 40 days to achieve a substantially weaker level of electrical function. These results suggest that rat neuron preparations may yield inferences that do not necessarily transfer to humans. © 2015 Wiley Periodicals, Inc.

Species-Specific 5 mC and 5 hmC Genomic Landscapes Indicate Epigenetic Contribution to Human Brain Evolution

PubMed Central

Madrid, Andy; Chopra, Pankaj; Alisch, Reid S.

2018-01-01

Human evolution from non-human primates has seen substantial change in the central nervous system, with the molecular mechanisms underlying human brain evolution remaining largely unknown. Methylation of cytosine at the fifth carbon (5-methylcytosine; 5 mC) is an essential epigenetic mark linked to neurodevelopment, as well as neurological disease. The emergence of another modified form of cytosine (5-hydroxymethylcytosine; 5 hmC) that is enriched in the brain further substantiates a role for these epigenetic marks in neurodevelopment, yet little is known about the evolutionary importance of these marks in brain development. Here, human and monkey brain tissue were profiled, identifying 5,516 and 4,070 loci that were differentially methylated and hydroxymethylated, respectively, between the species. Annotation of these loci to the human genome revealed genes critical for the development of the nervous system and that are associated with intelligence and higher cognitive functioning, such as RELN and GNAS. Moreover, ontological analyses of these differentially methylated and hydroxymethylated genes revealed a significant enrichment of neuronal/immunological–related processes, including neurogenesis and axon development. Finally, the sequences flanking the differentially methylated/hydroxymethylated loci contained a significant enrichment of binding sites for neurodevelopmentally important transcription factors (e.g., OTX1 and PITX1), suggesting that DNA methylation may regulate gene expression by mediating transcription factor binding on these transcripts. Together, these data support dynamic species-specific epigenetic contributions in the evolution and development of the human brain from non-human primates. PMID:29491831

Immunohistochemical localization of oxytocin receptors in human brain.

PubMed

Boccia, M L; Petrusz, P; Suzuki, K; Marson, L; Pedersen, C A

2013-12-03

The neuropeptide oxytocin (OT) regulates rodent, primate and human social behaviors and stress responses. OT binding studies employing (125)I-d(CH2)5-[Tyr(Me)2,Thr4,Tyr-NH2(9)] ornithine vasotocin ((125)I-OTA), has been used to locate and quantify OT receptors (OTRs) in numerous areas of the rat brain. This ligand has also been applied to locating OTRs in the human brain. The results of the latter studies, however, have been brought into question because of subsequent evidence that (125)I-OTA is much less selective for OTR vs. vasopressin receptors in the primate brain. Previously we used a monoclonal antibody directed toward a region of the human OTR to demonstrate selective immunostaining of cell bodies and fibers in the preoptic-anterior hypothalamic area and ventral septum of a cynomolgus monkey (Boccia et al., 2001). The present study employed the same monoclonal antibody to study the location of OTRs in tissue blocks containing cortical, limbic and brainstem areas dissected from fixed adult, human female brains. OTRs were visualized in discrete cell bodies and/or fibers in the central and basolateral regions of the amygdala, medial preoptic area (MPOA), anterior and ventromedial hypothalamus, olfactory nucleus, vertical limb of the diagonal band, ventrolateral septum, anterior cingulate and hypoglossal and solitary nuclei. OTR staining was not observed in the hippocampus (including CA2 and CA3), parietal cortex, raphe nucleus, nucleus ambiguus or pons. These results suggest that there are some similarities, but also important differences, in the locations of OTRs in human and rodent brains. Immunohistochemistry (IHC) utilizing a monoclonal antibody provides specific localization of OTRs in the human brain and thereby provides opportunity to further study OTR in human development and psychiatric conditions. Copyright © 2013 IBRO. Published by Elsevier Ltd. All rights reserved.

Mary Jane Hogue (1883-1962): A pioneer in human brain tissue culture.

PubMed

Zottoli, Steven J; Seyfarth, Ernst-August

2018-05-16

The ability to maintain human brain explants in tissue culture was a critical step in the use of these cells for the study of central nervous system disorders. Ross G. Harrison (1870-1959) was the first to successfully maintain frog medullary tissue in culture in 1907, but it took another 38 years before successful culture of human brain tissue was accomplished. One of the pioneers in this achievement was Mary Jane Hogue (1883-1962). Hogue was born into a Quaker family in 1883 in West Chester, Pennsylvania, and received her undergraduate degree from Goucher College in Baltimore, Maryland. Research with the developmental biologist Theodor Boveri (1862-1915) in Würzburg, Germany, resulted in her Ph.D. (1909). Hogue transitioned from studying protozoa to the culture of human brain tissue in the 1940s and 1950s, when she was one of the first to culture cells from human fetal, infant, and adult brain explants. We review Hogue's pioneering contributions to the study of human brain cells in culture, her putative identification of progenitor neuroblast and/or glioblast cells, and her use of the cultures to study the cytopathogenic effects of poliovirus. We also put Hogue's work in perspective by discussing how other women pioneers in tissue culture influenced Hogue and her research.

Optimization of Treatment Geometry to Reduce Normal Brain Dose in Radiosurgery of Multiple Brain Metastases with Single-Isocenter Volumetric Modulated Arc Therapy.

PubMed

Wu, Qixue; Snyder, Karen Chin; Liu, Chang; Huang, Yimei; Zhao, Bo; Chetty, Indrin J; Wen, Ning

2016-09-30

Treatment of patients with multiple brain metastases using a single-isocenter volumetric modulated arc therapy (VMAT) has been shown to decrease treatment time with the tradeoff of larger low dose to the normal brain tissue. We have developed an efficient Projection Summing Optimization Algorithm to optimize the treatment geometry in order to reduce dose to normal brain tissue for radiosurgery of multiple metastases with single-isocenter VMAT. The algorithm: (a) measures coordinates of outer boundary points of each lesion to be treated using the Eclipse Scripting Application Programming Interface, (b) determines the rotations of couch, collimator, and gantry using three matrices about the cardinal axes, (c) projects the outer boundary points of the lesion on to Beam Eye View projection plane, (d) optimizes couch and collimator angles by selecting the least total unblocked area for each specific treatment arc, and (e) generates a treatment plan with the optimized angles. The results showed significant reduction in the mean dose and low dose volume to normal brain, while maintaining the similar treatment plan qualities on the thirteen patients treated previously. The algorithm has the flexibility with regard to the beam arrangements and can be integrated in the treatment planning system for clinical application directly.

Transgenic Mice Carrying GLUD2 as a Tool for Studying the Expressional and the Functional Adaptation of this Positive Selected Gene in Human Brain Evolution.

PubMed

Plaitakis, Andreas; Kotzamani, Dimitra; Petraki, Zoe; Delidaki, Maria; Rinotas, Vagelis; Zaganas, Ioannis; Douni, Eleni; Sidiropoulou, Kyriaki; Spanaki, Cleanthe

2018-05-18

Human evolution is characterized by brain expansion and up-regulation of genes involved in energy metabolism and synaptic transmission, including the glutamate signaling pathway. Glutamate is the excitatory transmitter of neural circuits sub-serving cognitive functions, with glutamate-modulation of synaptic plasticity being central to learning and memory. GLUD2 is a novel positively-selected human gene involved in glutamatergic transmission and energy metabolism that underwent rapid evolutionary adaptation concomitantly with prefrontal cortex enlargement. Two evolutionary replacements (Gly456Ala and Arg443Ser) made hGDH2 resistant to GTP inhibition and allowed distinct regulation, enabling enhanced enzyme function under high glutamatergic system demands. GLUD2 adaptation may have contributed to unique human traits, but evidence for this is lacking. GLUD2 arose through retro-positioning of a processed GLUD1 mRNA to the X chromosome, a DNA replication mechanism that typically generates pseudogenes. However, by finding a suitable promoter, GLUD2 is thought to have gained expression in nerve and other tissues, where it adapted to their particular needs. Here we generated GLUD2 transgenic (Tg) mice by inserting in their genome a segment of the human X chromosome, containing the GLUD2 gene and its putative promoter. Double IF studies of Tg mouse brain revealed that the human gene is expressed in the host mouse brain in a pattern similar to that observed in human brain, thus providing credence to the above hypothesis. This expressional adaptation may have conferred novel role(s) on GLUD2 in human brain. Previous observations, also in GLUD2 Tg mice, generated and studied independently, showed that the non-redundant function of hGDH2 is markedly activated during early post-natal brain development, contributing to developmental changes in prefrontal cortex similar to those attributed to human divergence. Hence, GLUD2 adaptation may have influenced the evolutionary course taken by the human brain, but understanding the mechanism(s) involved remains challenging.

Describing the Neuron Axons Network of the Human Brain by Continuous Flow Models

NASA Astrophysics Data System (ADS)

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

2014-12-01

The multifractal spectrum Dq (Rényi dimensions) is used for the analysis and comparison between the Neuron Axons Network (NAN) of healthy and pathological human brains because it conveys information about the statistics in many scales, from the very rare to the most frequent network configurations. Comparison of the Fractional Anisotropy Magnetic Resonance Images between healthy and pathological brains is performed with and without noise reduction. Modelling the complex structure of the NAN in the human brain is undertaken using the dynamics of the Lorenz model in the chaotic regime. The Lorenz multifractal spectra capture well the human brain characteristics in the large negative q's which represent the rare network configurations. In order to achieve a closer approximation in the positive part of the spectrum (q > 0) two independent modifications are considered: a) redistribution of the dense parts of the Lorenz model's phase space into their neighbouring areas and b) inclusion of additive uniform noise in the Lorenz model. Both modifications, independently, drive the Lorenz spectrum closer to the human NAN one in the positive q region without destroying the already good correspondence of the negative spectra. The modelling process shows that the unmodified Lorenz model in its full chaotic regime has a phase space distribution with high fluctuations in its dense parts, while the fluctuations in the human brain NAN are smoother. The induced modifications (phase space redistribution or additive noise) moderate the fluctuations only in the positive part of the Lorenz spectrum leading to a faithful representation of the human brain axons network in all scales.

Human-like brain hemispheric dominance in birdsong learning.

PubMed

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

2012-07-31

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

A survey of human brain transcriptome diversity at the single cell level.

PubMed

Darmanis, Spyros; Sloan, Steven A; Zhang, Ye; Enge, Martin; Caneda, Christine; Shuer, Lawrence M; Hayden Gephart, Melanie G; Barres, Ben A; Quake, Stephen R

2015-06-09

The human brain is a tissue of vast complexity in terms of the cell types it comprises. Conventional approaches to classifying cell types in the human brain at single cell resolution have been limited to exploring relatively few markers and therefore have provided a limited molecular characterization of any given cell type. We used single cell RNA sequencing on 466 cells to capture the cellular complexity of the adult and fetal human brain at a whole transcriptome level. Healthy adult temporal lobe tissue was obtained during surgical procedures where otherwise normal tissue was removed to gain access to deeper hippocampal pathology in patients with medical refractory seizures. We were able to classify individual cells into all of the major neuronal, glial, and vascular cell types in the brain. We were able to divide neurons into individual communities and show that these communities preserve the categorization of interneuron subtypes that is typically observed with the use of classic interneuron markers. We then used single cell RNA sequencing on fetal human cortical neurons to identify genes that are differentially expressed between fetal and adult neurons and those genes that display an expression gradient that reflects the transition between replicating and quiescent fetal neuronal populations. Finally, we observed the expression of major histocompatibility complex type I genes in a subset of adult neurons, but not fetal neurons. The work presented here demonstrates the applicability of single cell RNA sequencing on the study of the adult human brain and constitutes a first step toward a comprehensive cellular atlas of the human brain.

Docosahexaenoic acid and human brain development: evidence that a dietary supply is needed for optimal development.

PubMed

Brenna, J Thomas; Carlson, Susan E

2014-12-01

Humans evolved a uniquely large brain among terrestrial mammals. Brain and nervous tissue is rich in the omega-3 polyunsaturated fatty acid (PUFA) docosahexaenoic acid (DHA). Docosahexaenoic acid is required for lower and high order functions in humans because of understood and emerging molecular mechanisms. Among brain components that depend on dietary components, DHA is limiting because its synthesis from terrestrial plant food precursors is low but its utilization when consumed in diet is very efficient. Negligible DHA is found in terrestrial plants, but in contrast, DHA is plentiful at the shoreline where it is made by single-celled organisms and plants, and in the seas supports development of very large marine mammal brains. Modern human brains accumulate DHA up to age 18, most aggressively from about half-way through gestation to about two years of age. Studies in modern humans and non-human primates show that modern infants consuming infant formulas that include only DHA precursors have lower DHA levels than for those with a source of preformed DHA. Functional measures show that infants consuming preformed DHA have improved visual and cognitive function. Dietary preformed DHA in the breast milk of modern mothers supports many-fold greater breast milk DHA than is found in the breast milk of vegans, a phenomenon linked to consumption of shore-based foods. Most current evidence suggests that the DHA-rich human brain required an ample and sustained source of dietary DHA to reach its full potential. Copyright © 2014 Elsevier Ltd. All rights reserved.

Metabolic constraint imposes tradeoff between body size and number of brain neurons in human evolution

PubMed Central

Fonseca-Azevedo, Karina; Herculano-Houzel, Suzana

2012-01-01

Despite a general trend for larger mammals to have larger brains, humans are the primates with the largest brain and number of neurons, but not the largest body mass. Why are great apes, the largest primates, not also those endowed with the largest brains? Recently, we showed that the energetic cost of the brain is a linear function of its numbers of neurons. Here we show that metabolic limitations that result from the number of hours available for feeding and the low caloric yield of raw foods impose a tradeoff between body size and number of brain neurons, which explains the small brain size of great apes compared with their large body size. This limitation was probably overcome in Homo erectus with the shift to a cooked diet. Absent the requirement to spend most available hours of the day feeding, the combination of newly freed time and a large number of brain neurons affordable on a cooked diet may thus have been a major positive driving force to the rapid increased in brain size in human evolution. PMID:23090991

Metabolic constraint imposes tradeoff between body size and number of brain neurons in human evolution.

PubMed

Fonseca-Azevedo, Karina; Herculano-Houzel, Suzana

2012-11-06

Despite a general trend for larger mammals to have larger brains, humans are the primates with the largest brain and number of neurons, but not the largest body mass. Why are great apes, the largest primates, not also those endowed with the largest brains? Recently, we showed that the energetic cost of the brain is a linear function of its numbers of neurons. Here we show that metabolic limitations that result from the number of hours available for feeding and the low caloric yield of raw foods impose a tradeoff between body size and number of brain neurons, which explains the small brain size of great apes compared with their large body size. This limitation was probably overcome in Homo erectus with the shift to a cooked diet. Absent the requirement to spend most available hours of the day feeding, the combination of newly freed time and a large number of brain neurons affordable on a cooked diet may thus have been a major positive driving force to the rapid increased in brain size in human evolution.

Control-related systems in the human brain

PubMed Central

Power, Jonathan D; Petersen, Steven E

2013-01-01

A fundamental question in cognitive neuroscience is how the human brain self-organizes to perform tasks. Multiple accounts of this self-organization are currently influential and in this article we survey one of these accounts. We begin by introducing a psychological model of task control and several neuroimaging signals it predicts. We then discuss where such signals are found across tasks with emphasis on brain regions where multiple control signals are present. We then present results derived from spontaneous task-free functional connectivity between control-related regions that dovetail with distinctions made by control signals present in these regions, leading to a proposal that there are at least two task control systems in the brain. This prompts consideration of whether and how such control systems distinguish themselves from other brain regions in a whole-brain context. We present evidence from whole-brain networks that such distinctions do occur and that control systems comprise some of the basic system-level organizational elements of the human brain. We close with observations from the whole-brain networks that may suggest parsimony between multiple accounts of cognitive control. PMID:23347645

Independent EEG Sources Are Dipolar

PubMed Central

Delorme, Arnaud; Palmer, Jason; Onton, Julie; Oostenveld, Robert; Makeig, Scott

2012-01-01

Independent component analysis (ICA) and blind source separation (BSS) methods are increasingly used to separate individual brain and non-brain source signals mixed by volume conduction in electroencephalographic (EEG) and other electrophysiological recordings. We compared results of decomposing thirteen 71-channel human scalp EEG datasets by 22 ICA and BSS algorithms, assessing the pairwise mutual information (PMI) in scalp channel pairs, the remaining PMI in component pairs, the overall mutual information reduction (MIR) effected by each decomposition, and decomposition ‘dipolarity’ defined as the number of component scalp maps matching the projection of a single equivalent dipole with less than a given residual variance. The least well-performing algorithm was principal component analysis (PCA); best performing were AMICA and other likelihood/mutual information based ICA methods. Though these and other commonly-used decomposition methods returned many similar components, across 18 ICA/BSS algorithms mean dipolarity varied linearly with both MIR and with PMI remaining between the resulting component time courses, a result compatible with an interpretation of many maximally independent EEG components as being volume-conducted projections of partially-synchronous local cortical field activity within single compact cortical domains. To encourage further method comparisons, the data and software used to prepare the results have been made available (http://sccn.ucsd.edu/wiki/BSSComparison). PMID:22355308

Increased expression of protein kinase A inhibitor alpha (PKI-alpha) and decreased PKA-regulated genes in chronic intermittent alcohol exposure.

PubMed

Repunte-Canonigo, Vez; Lutjens, Robert; van der Stap, Lena D; Sanna, Pietro Paolo

2007-03-23

Intermittent models of alcohol exposure that mimic human patterns of alcohol consumption produce profound physiological and biochemical changes and induce rapid increases in alcohol self-administration. We used high-density oligonucleotide microarrays to investigate gene expression changes during chronic intermittent alcohol exposure in three brain regions that receive mesocorticolimbic dopaminergic projections and that are believed to be involved in alcohol's reinforcing actions: the medial prefrontal cortex, the nucleus accumbens and the amygdala. An independent replication of the experiment was used for RT-PCR validation of the microarray results. The protein kinase A inhibitor alpha (PKI-alpha, Pkia), a member of the endogenous PKI family implicated in reducing nuclear PKA activity, was found to be increased in all three regions tested. Conversely, we observed a downregulation of the expression of several PKA-regulated transcripts in one or more of the brain regions studied, including the activity and neurotransmitter-regulated early gene (Ania) - 1, -3, -7, -8, the transcription factors Egr1 and NGFI-B (Nr4a1) and the neuropeptide NPY. Reduced expression of PKA-regulated genes in mesocorticolimbic projection areas may have motivational significance in the rapid increase in alcohol self-administration induced by intermittent alcohol exposure.

Interdisciplinary collaboration in action: tracking the signal, tracing the noise

PubMed Central

Callard, Felicity; Fitzgerald, Des; Woods, Angela

2016-01-01

Interdisciplinarity is often framed as an unquestioned good within and beyond the academy, one to be encouraged by funders and research institutions alike. And yet there is little research on how interdisciplinary projects actually work—and do not work—in practice, particularly within and across the social sciences and humanities. This article centres on “Hubbub”, the first interdisciplinary 2-year research residency of The Hub at Wellcome Collection, which is investigating rest and its opposites in neuroscience, mental health, the arts and the everyday. The article describes how Hubbub is tracing, capturing and reflecting on practices of interdisciplinarity across its large, dispersed team of collaborators, who work across the social sciences, humanities, arts, mind and brain sciences, and public engagement. We first describe the distinctiveness of Hubbub (a project designed for a particular space, and one in which the arts are not positioned as simply illustrating or disseminating the research of the scientists), and then outline three techniques Hubbub has developed to map interdisciplinary collaboration in the making: (1) ethnographic analysis; (2) “In the Diary Room”, an aesthetics of collaboration designed to harness and capture affective dynamics within a large, complex project; and (3) the Hubbub Collaboration Questionnaire, which yields quantitative and qualitative data, as well as a social network analysis of collaborators. We conclude by considering some themes that other inter-disciplinary projects might draw on for their own logics of tracking and tracing. This article forms part of an ongoing thematic collection dedicated to interdisciplinary research. PMID:27516896

Brain shape in human microcephalics and Homo floresiensis.

PubMed

Falk, Dean; Hildebolt, Charles; Smith, Kirk; Morwood, M J; Sutikna, Thomas; Jatmiko; Saptomo, E Wayhu; Imhof, Herwig; Seidler, Horst; Prior, Fred

2007-02-13

Because the cranial capacity of LB1 (Homo floresiensis) is only 417 cm(3), some workers propose that it represents a microcephalic Homo sapiens rather than a new species. This hypothesis is difficult to assess, however, without a clear understanding of how brain shape of microcephalics compares with that of normal humans. We compare three-dimensional computed tomographic reconstructions of the internal braincases (virtual endocasts that reproduce details of external brain morphology, including cranial capacities and shape) from a sample of 9 microcephalic humans and 10 normal humans. Discriminant and canonical analyses are used to identify two variables that classify normal and microcephalic humans with 100% success. The classification functions classify the virtual endocast from LB1 with normal humans rather than microcephalics. On the other hand, our classification functions classify a pathological H. sapiens specimen that, like LB1, represents an approximately 3-foot-tall adult female and an adult Basuto microcephalic woman that is alleged to have an endocast similar to LB1's with the microcephalic humans. Although microcephaly is genetically and clinically variable, virtual endocasts from our highly heterogeneous sample share similarities in protruding and proportionately large cerebella and relatively narrow, flattened orbital surfaces compared with normal humans. These findings have relevance for hypotheses regarding the genetic substrates of hominin brain evolution and may have medical diagnostic value. Despite LB1's having brain shape features that sort it with normal humans rather than microcephalics, other shape features and its small brain size are consistent with its assignment to a separate species.

A pediatric brain structure atlas from T1-weighted MR images

NASA Astrophysics Data System (ADS)

Shan, Zuyao Y.; Parra, Carlos; Ji, Qing; Ogg, Robert J.; Zhang, Yong; Laningham, Fred H.; Reddick, Wilburn E.

2006-03-01

In this paper, we have developed a digital atlas of the pediatric human brain. Human brain atlases, used to visualize spatially complex structures of the brain, are indispensable tools in model-based segmentation and quantitative analysis of brain structures. However, adult brain atlases do not adequately represent the normal maturational patterns of the pediatric brain, and the use of an adult model in pediatric studies may introduce substantial bias. Therefore, we proposed to develop a digital atlas of the pediatric human brain in this study. The atlas was constructed from T1 weighted MR data set of a 9 year old, right-handed girl. Furthermore, we extracted and simplified boundary surfaces of 25 manually defined brain structures (cortical and subcortical) based on surface curvature. Higher curvature surfaces were simplified with more reference points; lower curvature surfaces, with fewer. We constructed a 3D triangular mesh model for each structure by triangulation of the structure's reference points. Kappa statistics (cortical, 0.97; subcortical, 0.91) indicated substantial similarities between the mesh-defined and the original volumes. Our brain atlas and structural mesh models (www.stjude.org/BrainAtlas) can be used to plan treatment, to conduct knowledge and modeldriven segmentation, and to analyze the shapes of brain structures in pediatric patients.

Genetic compendium of 1511 human brains available through the UK Medical Research Council Brain Banks Network Resource.

PubMed

Keogh, Michael J; Wei, Wei; Wilson, Ian; Coxhead, Jon; Ryan, Sarah; Rollinson, Sara; Griffin, Helen; Kurzawa-Akanbi, Marzena; Santibanez-Koref, Mauro; Talbot, Kevin; Turner, Martin R; McKenzie, Chris-Anne; Troakes, Claire; Attems, Johannes; Smith, Colin; Al Sarraj, Safa; Morris, Chris M; Ansorge, Olaf; Pickering-Brown, Stuart; Ironside, James W; Chinnery, Patrick F

2017-01-01

Given the central role of genetic factors in the pathogenesis of common neurodegenerative disorders, it is critical that mechanistic studies in human tissue are interpreted in a genetically enlightened context. To address this, we performed exome sequencing and copy number variant analysis on 1511 frozen human brains with a diagnosis of Alzheimer's disease (AD, n = 289), frontotemporal dementia/amyotrophic lateral sclerosis (FTD/ALS, n = 252), Creutzfeldt-Jakob disease (CJD, n = 239), Parkinson's disease (PD, n = 39), dementia with Lewy bodies (DLB, n = 58), other neurodegenerative, vascular, or neurogenetic disorders (n = 266), and controls with no significant neuropathology (n = 368). Genomic DNA was extracted from brain tissue in all cases before exome sequencing (Illumina Nextera 62 Mb capture) with variants called by FreeBayes; copy number variant (CNV) analysis (Illumina HumanOmniExpress-12 BeadChip); C9orf72 repeat expansion detection; and APOE genotyping. Established or likely pathogenic heterozygous, compound heterozygous, or homozygous variants, together with the C9orf72 hexanucleotide repeat expansions and a copy number gain of APP, were found in 61 brains. In addition to known risk alleles in 349 brains (23.9% of 1461 undergoing exome sequencing), we saw an association between rare variants in GRN and DLB. Rare CNVs were found in <1.5% of brains, including copy number gains of PRPH that were overrepresented in AD. Clinical, pathological, and genetic data are available, enabling the retrieval of specific frozen brains through the UK Medical Research Council Brain Banks Network. This allows direct access to pathological and control human brain tissue based on an individual's genetic architecture, thus enabling the functional validation of known genetic risk factors and potentially pathogenic alleles identified in future studies. © 2017 Keogh et al.; Published by Cold Spring Harbor Laboratory Press.

Mechanisms of Neurodegeneration and Regeneration in Alcoholism

PubMed Central

Crews, Fulton T.; Nixon, Kim

2009-01-01

Aims: This is a review of preclinical studies covering alcohol-induced brain neuronal death and loss of neurogenesis as well as abstinence-induced brain cell genesis, e.g. brain regeneration. Efforts are made to relate preclinical studies to human studies. Methods: The studies described are preclinical rat experiments using a 4-day binge ethanol treatment known to induce physical dependence to ethanol. Neurodegeneration and cognitive deficits following binge treatment mimic the mild degeneration and cognitive deficits found in humans. Various histological methods are used to follow brain regional degeneration and regeneration. Results: Alcohol-induced degeneration occurs due to neuronal death during alcohol intoxication. Neuronal death is related to increases in oxidative stress in brain that coincide with the induction of proinflammatory cytokines and oxidative enzymes that insult brain. Degeneration is associated with increased NF-κB proinflammatory transcription and decreased CREB transcription. Corticolimbic brain regions are most sensitive to binge-induced degeneration and induce relearning deficits. Drugs that block oxidative stress and NF-κB transcription or increase CREB transcription block binge-induced neurodegeneration, inhibition of neurogenesis and proinflammatory enzyme induction. Regeneration of brain occurs during abstinence following binge ethanol treatment. Bursts of proliferating cells occur across multiple brain regions, with many new microglia across brain after months of abstinence and many new neurons in neurogenic hippocampal dentate gyrus. Brain regeneration may be important to sustain abstinence in humans. Conclusions: Alcohol-induced neurodegeneration occurs primarily during intoxication and is related to increased oxidative stress and proinflammatory proteins that are neurotoxic. Abstinence after binge ethanol intoxication results in brain cell genesis that could contribute to the return of brain function and structure found in abstinent humans. PMID:18940959

Hand Function in Relation to Brain Lesions and Corticomotor-Projection Pattern in Children with Unilateral Cerebral Palsy

ERIC Educational Resources Information Center

Holmstrom, Linda; Vollmer, Brigitte; Tedroff, Kristina; Islam, Mominul; Persson, Jonas Ke; Kits, Annika; Forssberg, Hans; Eliasson, Ann-Christin

2010-01-01

Aim: To investigate relationships between hand function, brain lesions, and corticomotor projections in children with unilateral cerebral palsy (CP). Method: The study included 17 children (nine males, eight females; mean age 11.4 [SD 2.4] range 7-16y), with unilateral CP at Gross Motor Function Classification System level I and Manual Ability…