Sample records for mapping human brain

  1. Brain/MINDS: brain-mapping project in Japan

    PubMed Central

    Okano, Hideyuki; Miyawaki, Atsushi; Kasai, Kiyoto

    2015-01-01

    There is an emerging interest in brain-mapping projects in countries across the world, including the USA, Europe, Australia and China. In 2014, Japan started a brain-mapping project called Brain Mapping by Integrated Neurotechnologies for Disease Studies (Brain/MINDS). Brain/MINDS aims to map the structure and function of neuronal circuits to ultimately understand the vast complexity of the human brain, and takes advantage of a unique non-human primate animal model, the common marmoset (Callithrix jacchus). In Brain/MINDS, the RIKEN Brain Science Institute acts as a central institute. The objectives of Brain/MINDS can be categorized into the following three major subject areas: (i) structure and functional mapping of a non-human primate brain (the marmoset brain); (ii) development of innovative neurotechnologies for brain mapping; and (iii) human brain mapping; and clinical research. Brain/MINDS researchers are highly motivated to identify the neuronal circuits responsible for the phenotype of neurological and psychiatric disorders, and to understand the development of these devastating disorders through the integration of these three subject areas. PMID:25823872

  2. Brain-mapping projects using the common marmoset.

    PubMed

    Okano, Hideyuki; Mitra, Partha

    2015-04-01

    Globally, there is an increasing interest in brain-mapping projects, including the Brain Research through Advancing Innovative Neurotechnologies (BRAIN) Initiative project in the USA, the Human Brain Project (HBP) in Europe, and the Brain Mapping by Integrated Neurotechnologies for Disease Studies (Brain/MINDS) project in Japan. These projects aim to map the structure and function of neuronal circuits to ultimately understand the vast complexity of the human brain. Brain/MINDS is focused on structural and functional mapping of the common marmoset (Callithrix jacchus) brain. This non-human primate has numerous advantages for brain mapping, including a well-developed frontal cortex and a compact brain size, as well as the availability of transgenic technologies. In the present review article, we discuss strategies for structural and functional mapping of the marmoset brain and the relation of the common marmoset to other animals models. Copyright © 2014 The Authors. Published by Elsevier Ireland Ltd.. All rights reserved.

  3. 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.

  4. Quantitative susceptibility mapping of human brain at 3T: a multisite reproducibility study.

    PubMed

    Lin, P-Y; Chao, T-C; Wu, M-L

    2015-03-01

    Quantitative susceptibility mapping of the human brain has demonstrated strong potential in examining iron deposition, which may help in investigating possible brain pathology. This study assesses the reproducibility of quantitative susceptibility mapping across different imaging sites. In this study, the susceptibility values of 5 regions of interest in the human brain were measured on 9 healthy subjects following calibration by using phantom experiments. Each of the subjects was imaged 5 times on 1 scanner with the same procedure repeated on 3 different 3T systems so that both within-site and cross-site quantitative susceptibility mapping precision levels could be assessed. Two quantitative susceptibility mapping algorithms, similar in principle, one by using iterative regularization (iterative quantitative susceptibility mapping) and the other with analytic optimal solutions (deterministic quantitative susceptibility mapping), were implemented, and their performances were compared. Results show that while deterministic quantitative susceptibility mapping had nearly 700 times faster computation speed, residual streaking artifacts seem to be more prominent compared with iterative quantitative susceptibility mapping. With quantitative susceptibility mapping, the putamen, globus pallidus, and caudate nucleus showed smaller imprecision on the order of 0.005 ppm, whereas the red nucleus and substantia nigra, closer to the skull base, had a somewhat larger imprecision of approximately 0.01 ppm. Cross-site errors were not significantly larger than within-site errors. Possible sources of estimation errors are discussed. The reproducibility of quantitative susceptibility mapping in the human brain in vivo is regionally dependent, and the precision levels achieved with quantitative susceptibility mapping should allow longitudinal and multisite studies such as aging-related changes in brain tissue magnetic susceptibility. © 2015 by American Journal of Neuroradiology.

  5. 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.

  6. 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

  7. Intraoperative Functional Ultrasound Imaging of Human Brain Activity.

    PubMed

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

    2017-08-04

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

  8. Mapping Prefrontal Cortex Functions in Human Infancy

    ERIC Educational Resources Information Center

    Grossmann, Tobias

    2013-01-01

    It has long been thought that the prefrontal cortex, as the seat of most higher brain functions, is functionally silent during most of infancy. This review highlights recent work concerned with the precise mapping (localization) of brain activation in human infants, providing evidence that prefrontal cortex exhibits functional activation much…

  9. Researching and Reducing the Health Burden of Stroke

    MedlinePlus

    ... the result of continuing research to map the brain and interface it with a computer to enable stroke patients to regain function. How important is the new effort to map the human brain? The brain is more complex than any computer ...

  10. Variability in Cortical Representations of Speech Sound Perception

    ERIC Educational Resources Information Center

    Boatman, Dana F.

    2007-01-01

    Recent brain mapping studies have provided new insights into the cortical systems that mediate human speech perception. Electrocortical stimulation mapping (ESM) is a brain mapping method that is used clinically to localize cortical functions in neurosurgical patients. Recent ESM studies have yielded new insights into the cortical systems that…

  11. Body Maps in the Infant Brain

    PubMed Central

    Marshall, Peter J.; Meltzoff, Andrew N.

    2015-01-01

    Researchers have examined representations of the body in the adult brain, but relatively little attention has been paid to ontogenetic aspects of neural body maps in human infants. Novel applications of methods for recording brain activity in infants are delineating cortical body maps in the first months of life. Body maps may facilitate infants’ registration of similarities between self and other—an ability that is foundational to developing social cognition. Alterations in interpersonal aspects of body representations might also contribute to social deficits in certain neurodevelopmental disorders. PMID:26231760

  12. Cerebral cartography and connectomics

    PubMed Central

    Sporns, Olaf

    2015-01-01

    Cerebral cartography and connectomics pursue similar goals in attempting to create maps that can inform our understanding of the structural and functional organization of the cortex. Connectome maps explicitly aim at representing the brain as a complex network, a collection of nodes and their interconnecting edges. This article reflects on some of the challenges that currently arise in the intersection of cerebral cartography and connectomics. Principal challenges concern the temporal dynamics of functional brain connectivity, the definition of areal parcellations and their hierarchical organization into large-scale networks, the extension of whole-brain connectivity to cellular-scale networks, and the mapping of structure/function relations in empirical recordings and computational models. Successfully addressing these challenges will require extensions of methods and tools from network science to the mapping and analysis of human brain connectivity data. The emerging view that the brain is more than a collection of areas, but is fundamentally operating as a complex networked system, will continue to drive the creation of ever more detailed and multi-modal network maps as tools for on-going exploration and discovery in human connectomics. PMID:25823870

  13. Mapping fetal brain development in utero using magnetic resonance imaging: the Big Bang of brain mapping.

    PubMed

    Studholme, Colin

    2011-08-15

    The development of tools to construct and investigate probabilistic maps of the adult human brain from magnetic resonance imaging (MRI) has led to advances in both basic neuroscience and clinical diagnosis. These tools are increasingly being applied to brain development in adolescence and childhood, and even to neonatal and premature neonatal imaging. Even earlier in development, parallel advances in clinical fetal MRI have led to its growing use as a tool in challenging medical conditions. This has motivated new engineering developments encompassing optimal fast MRI scans and techniques derived from computer vision, the combination of which allows full 3D imaging of the moving fetal brain in utero without sedation. These promise to provide a new and unprecedented window into early human brain growth. This article reviews the developments that have led us to this point, examines the current state of the art in the fields of fast fetal imaging and motion correction, and describes the tools to analyze dynamically changing fetal brain structure. New methods to deal with developmental tissue segmentation and the construction of spatiotemporal atlases are examined, together with techniques to map fetal brain growth patterns.

  14. Quantitative Susceptibility Mapping of Human Brain Reflects Spatial Variation in Tissue Composition

    PubMed Central

    Li, Wei; Wu, Bing; Liu, Chunlei

    2011-01-01

    Image phase from gradient echo MRI provides a unique contrast that reflects brain tissue composition variations, such as iron and myelin distribution. Phase imaging is emerging as a powerful tool for the investigation of functional brain anatomy and disease diagnosis. However, the quantitative value of phase is compromised by its nonlocal and orientation dependent properties. There is an increasing need for reliable quantification of magnetic susceptibility, the intrinsic property of tissue. In this study, we developed a novel and accurate susceptibility mapping method that is also phase-wrap insensitive. The proposed susceptibility mapping method utilized two complementary equations: (1) the Fourier relationship of phase and magnetic susceptibility; and (2) the first-order partial derivative of the first equation in the spatial frequency domain. In numerical simulation, this method reconstructed the susceptibility map almost free of streaking artifact. Further, the iterative implementation of this method allowed for high quality reconstruction of susceptibility maps of human brain in vivo. The reconstructed susceptibility map provided excellent contrast of iron-rich deep nuclei and white matter bundles from surrounding tissues. Further, it also revealed anisotropic magnetic susceptibility in brain white matter. Hence, the proposed susceptibility mapping method may provide a powerful tool for the study of brain physiology and pathophysiology. Further elucidation of anisotropic magnetic susceptibility in vivo may allow us to gain more insight into the white matter microarchitectures. PMID:21224002

  15. White matter tractography using diffusion tensor deflection.

    PubMed

    Lazar, Mariana; Weinstein, David M; Tsuruda, Jay S; Hasan, Khader M; Arfanakis, Konstantinos; Meyerand, M Elizabeth; Badie, Benham; Rowley, Howard A; Haughton, Victor; Field, Aaron; Alexander, Andrew L

    2003-04-01

    Diffusion tensor MRI provides unique directional diffusion information that can be used to estimate the patterns of white matter connectivity in the human brain. In this study, the behavior of an algorithm for white matter tractography is examined. The algorithm, called TEND, uses the entire diffusion tensor to deflect the estimated fiber trajectory. Simulations and imaging experiments on in vivo human brains were performed to investigate the behavior of the tractography algorithm. The simulations show that the deflection term is less sensitive than the major eigenvector to image noise. In the human brain imaging experiments, estimated tracts were generated in corpus callosum, corticospinal tract, internal capsule, corona radiata, superior longitudinal fasciculus, inferior longitudinal fasciculus, fronto-occipital fasciculus, and uncinate fasciculus. This approach is promising for mapping the organizational patterns of white matter in the human brain as well as mapping the relationship between major fiber trajectories and the location and extent of brain lesions. Copyright 2003 Wiley-Liss, Inc.

  16. 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.

  17. Balanced steady state free precession for arterial spin labeling MRI: Initial experience for blood flow mapping in human brain, retina, and kidney.

    PubMed

    Park, Sung-Hong; Wang, Danny J J; Duong, Timothy Q

    2013-09-01

    We implemented pseudo-continuous ASL (pCASL) with 2D and 3D balanced steady state free precession (bSSFP) readout for mapping blood flow in the human brain, retina, and kidney, free of distortion and signal dropout, which are typically observed in the most commonly used echo-planar imaging acquisition. High resolution functional brain imaging in the human visual cortex was feasible with 3D bSSFP pCASL. Blood flow of the human retina could be imaged with pCASL and bSSFP in conjunction with a phase cycling approach to suppress the banding artifacts associated with bSSFP. Furthermore, bSSFP based pCASL enabled us to map renal blood flow within a single breath hold. Control and test-retest experiments suggested that the measured blood flow values in retina and kidney were reliable. Because there is no specific imaging tool for mapping human retina blood flow and the standard contrast agent technique for mapping renal blood flow can cause problems for patients with kidney dysfunction, bSSFP based pCASL may provide a useful tool for the diagnosis of retinal and renal diseases and can complement existing imaging techniques. Copyright © 2013 Elsevier Inc. All rights reserved.

  18. Cerebral cartography and connectomics.

    PubMed

    Sporns, Olaf

    2015-05-19

    Cerebral cartography and connectomics pursue similar goals in attempting to create maps that can inform our understanding of the structural and functional organization of the cortex. Connectome maps explicitly aim at representing the brain as a complex network, a collection of nodes and their interconnecting edges. This article reflects on some of the challenges that currently arise in the intersection of cerebral cartography and connectomics. Principal challenges concern the temporal dynamics of functional brain connectivity, the definition of areal parcellations and their hierarchical organization into large-scale networks, the extension of whole-brain connectivity to cellular-scale networks, and the mapping of structure/function relations in empirical recordings and computational models. Successfully addressing these challenges will require extensions of methods and tools from network science to the mapping and analysis of human brain connectivity data. The emerging view that the brain is more than a collection of areas, but is fundamentally operating as a complex networked system, will continue to drive the creation of ever more detailed and multi-modal network maps as tools for on-going exploration and discovery in human connectomics. © 2015 The Author(s) Published by the Royal Society. All rights reserved.

  19. Spatial cluster analysis of nanoscopically mapped serotonin receptors for classification of fixed brain tissue

    NASA Astrophysics Data System (ADS)

    Sams, Michael; Silye, Rene; Göhring, Janett; Muresan, Leila; Schilcher, Kurt; Jacak, Jaroslaw

    2014-01-01

    We present a cluster spatial analysis method using nanoscopic dSTORM images to determine changes in protein cluster distributions within brain tissue. Such methods are suitable to investigate human brain tissue and will help to achieve a deeper understanding of brain disease along with aiding drug development. Human brain tissue samples are usually treated postmortem via standard fixation protocols, which are established in clinical laboratories. Therefore, our localization microscopy-based method was adapted to characterize protein density and protein cluster localization in samples fixed using different protocols followed by common fluorescent immunohistochemistry techniques. The localization microscopy allows nanoscopic mapping of serotonin 5-HT1A receptor groups within a two-dimensional image of a brain tissue slice. These nanoscopically mapped proteins can be confined to clusters by applying the proposed statistical spatial analysis. Selected features of such clusters were subsequently used to characterize and classify the tissue. Samples were obtained from different types of patients, fixed with different preparation methods, and finally stored in a human tissue bank. To verify the proposed method, samples of a cryopreserved healthy brain have been compared with epitope-retrieved and paraffin-fixed tissues. Furthermore, samples of healthy brain tissues were compared with data obtained from patients suffering from mental illnesses (e.g., major depressive disorder). Our work demonstrates the applicability of localization microscopy and image analysis methods for comparison and classification of human brain tissues at a nanoscopic level. Furthermore, the presented workflow marks a unique technological advance in the characterization of protein distributions in brain tissue sections.

  20. Mapping Neurodegenerative Disease Onset and Progression.

    PubMed

    Seeley, William W

    2017-08-01

    Brain networks have been of long-standing interest to neurodegeneration researchers, including but not limited to investigators focusing on conventional prion diseases, which are known to propagate along neural pathways. Tools for human network mapping, however, remained inadequate, limiting our understanding of human brain network architecture and preventing clinical research applications. Until recently, neuropathological studies were the only viable approach to mapping disease onset and progression in humans but required large autopsy cohorts and laborious methods for whole-brain sectioning and staining. Despite important advantages, postmortem studies cannot address in vivo, physiological, or longitudinal questions and have limited potential to explore early-stage disease except for the most common disorders. Emerging in vivo network-based neuroimaging strategies have begun to address these issues, providing data that complement the neuropathological tradition. Overall, findings to date highlight several fundamental principles of neurodegenerative disease anatomy and pathogenesis, as well as some enduring mysteries. These principles and mysteries provide a road map for future research. Copyright © 2017 Cold Spring Harbor Laboratory Press; all rights reserved.

  1. High and ultra-high resolution metabolite mapping of the human brain using 1H FID MRSI at 9.4T.

    PubMed

    Nassirpour, Sahar; Chang, Paul; Henning, Anke

    2018-03-01

    Magnetic resonance spectroscopic imaging (MRSI) is a promising technique for mapping the spatial distribution of multiple metabolites in the human brain. These metabolite maps can be used as a diagnostic tool to gain insight into several biochemical processes and diseases in the brain. In comparison to lower field strengths, MRSI at ultra-high field strengths benefits from a higher signal to noise ratio (SNR) as well as higher chemical shift dispersion, and hence spectral resolution. This study combines the benefits of an ultra-high field magnet with the advantages of an ultra-short TE and TR single-slice FID-MRSI sequence (such as negligible J-evolution and loss of SNR due to T 2 relaxation effects) and presents the first metabolite maps acquired at 9.4T in the healthy human brain at both high (voxel size of 97.6µL) and ultra-high (voxel size of 24.4µL) spatial resolutions in a scan time of 11 and 46min respectively. In comparison to lower field strengths, more anatomically-detailed maps with higher SNR from a larger number of metabolites are shown. A total of 12 metabolites including glutamate (Glu), glutamine (Gln), N-acetyl-aspartyl-glutamate (NAAG), Gamma-aminobutyric acid (GABA) and glutathione (GSH) are reliably mapped. Comprehensive description of the methodology behind these maps is provided. Copyright © 2016 Elsevier Inc. All rights reserved.

  2. aMAP is a validated pipeline for registration and segmentation of high-resolution mouse brain data

    PubMed Central

    Niedworok, Christian J.; Brown, Alexander P. Y.; Jorge Cardoso, M.; Osten, Pavel; Ourselin, Sebastien; Modat, Marc; Margrie, Troy W.

    2016-01-01

    The validation of automated image registration and segmentation is crucial for accurate and reliable mapping of brain connectivity and function in three-dimensional (3D) data sets. While validation standards are necessarily high and routinely met in the clinical arena, they have to date been lacking for high-resolution microscopy data sets obtained from the rodent brain. Here we present a tool for optimized automated mouse atlas propagation (aMAP) based on clinical registration software (NiftyReg) for anatomical segmentation of high-resolution 3D fluorescence images of the adult mouse brain. We empirically evaluate aMAP as a method for registration and subsequent segmentation by validating it against the performance of expert human raters. This study therefore establishes a benchmark standard for mapping the molecular function and cellular connectivity of the rodent brain. PMID:27384127

  3. 78 FR 66611 - National Alzheimer's Disease Awareness Month, 2013

    Federal Register 2010, 2011, 2012, 2013, 2014

    2013-11-05

    ... Proclamation Alzheimer's disease is an irreversible and progressive brain disease that slowly erodes precious... year, I proposed the Brain Research through Advancing Innovative Neurotechnologies (BRAIN) Initiative, which aims to revolutionize our understanding of the human brain. By mapping the brain, we hope to...

  4. BrainMap VBM: An environment for structural meta-analysis.

    PubMed

    Vanasse, Thomas J; Fox, P Mickle; Barron, Daniel S; Robertson, Michaela; Eickhoff, Simon B; Lancaster, Jack L; Fox, Peter T

    2018-05-02

    The BrainMap database is a community resource that curates peer-reviewed, coordinate-based human neuroimaging literature. By pairing the results of neuroimaging studies with their relevant meta-data, BrainMap facilitates coordinate-based meta-analysis (CBMA) of the neuroimaging literature en masse or at the level of experimental paradigm, clinical disease, or anatomic location. Initially dedicated to the functional, task-activation literature, BrainMap is now expanding to include voxel-based morphometry (VBM) studies in a separate sector, titled: BrainMap VBM. VBM is a whole-brain, voxel-wise method that measures significant structural differences between or within groups which are reported as standardized, peak x-y-z coordinates. Here we describe BrainMap VBM, including the meta-data structure, current data volume, and automated reverse inference functions (region-to-disease profile) of this new community resource. CBMA offers a robust methodology for retaining true-positive and excluding false-positive findings across studies in the VBM literature. As with BrainMap's functional database, BrainMap VBM may be synthesized en masse or at the level of clinical disease or anatomic location. As a use-case scenario for BrainMap VBM, we illustrate a trans-diagnostic data-mining procedure wherein we explore the underlying network structure of 2,002 experiments representing over 53,000 subjects through independent components analysis (ICA). To reduce data-redundancy effects inherent to any database, we demonstrate two data-filtering approaches that proved helpful to ICA. Finally, we apply hierarchical clustering analysis (HCA) to measure network- and disease-specificity. This procedure distinguished psychiatric from neurological diseases. We invite the neuroscientific community to further exploit BrainMap VBM with other modeling approaches. © 2018 Wiley Periodicals, Inc.

  5. 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

  6. 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.

  7. 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

  8. 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.

  9. Multichannel optical mapping: investigation of depth information

    NASA Astrophysics Data System (ADS)

    Sase, Ichiro; Eda, Hideo; Seiyama, Akitoshi; Tanabe, Hiroki C.; Takatsuki, Akira; Yanagida, Toshio

    2001-06-01

    Near infrared (NIR) light has become a powerful tool for non-invasive imaging of human brain activity. Many systems have been developed to capture the changes in regional brain blood flow and hemoglobin oxygenation, which occur in the human cortex in response to neural activity. We have developed a multi-channel reflectance imaging system, which can be used as a `mapping device' and also as a `multi-channel spectrophotometer'. In the present study, we visualized changes in the hemodynamics of the human occipital region in multiple ways. (1) Stimulating left and right primary visual cortex independently by showing sector shaped checkerboards sequentially over the contralateral visual field, resulted in corresponding changes in the hemodynamics observed by `mapping' measurement. (2) Simultaneous measurement of functional-MRI and NIR (changes in total hemoglobin) during visual stimulation showed good spatial and temporal correlation with each other. (3) Placing multiple channels densely over the occipital region demonstrated spatial patterns more precisely, and depth information was also acquired by placing each pair of illumination and detection fibers at various distances. These results indicate that optical method can provide data for 3D analysis of human brain functions.

  10. 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

  11. Protecting peer review: correspondence chronology and ethical analysis regarding Logothetis vs. Shmuel and Leopold.

    PubMed

    Fox, Peter T; Bullmore, Ed; Bandettini, Peter A; Lancaster, Jack L

    2009-02-01

    Editors of scientific journals are ethically bound to provide a fair and impartial peer-review process and to protect the rights of contributing authors to publish research results. If, however, a dispute arises among investigators regarding data ownership and the right to publish, the ethical responsibilities of journal editors become more complex. The editors of Human Brain Mapping recently had the unusual experience of learning of an ongoing dispute regarding data-access rights pertaining to a manuscript already accepted for publication. Herein the editors describe the nature of the dispute, the steps taken to explore and resolve the conflict, and discuss the ethical principles that govern such circumstances. Drawing on this experience and with the goal of avoiding future controversies, the editors have formulated a Data Rights Policy and a Data Rights Procedure for Human Brain Mapping. Human Brain Mapping adopts this policy effective immediately and respectfully suggests that other journals consider adopting this or similar policies.

  12. Localization of MEG human brain responses to retinotopic visual stimuli with contrasting source reconstruction approaches

    PubMed Central

    Cicmil, Nela; Bridge, Holly; Parker, Andrew J.; Woolrich, Mark W.; Krug, Kristine

    2014-01-01

    Magnetoencephalography (MEG) allows the physiological recording of human brain activity at high temporal resolution. However, spatial localization of the source of the MEG signal is an ill-posed problem as the signal alone cannot constrain a unique solution and additional prior assumptions must be enforced. An adequate source reconstruction method for investigating the human visual system should place the sources of early visual activity in known locations in the occipital cortex. We localized sources of retinotopic MEG signals from the human brain with contrasting reconstruction approaches (minimum norm, multiple sparse priors, and beamformer) and compared these to the visual retinotopic map obtained with fMRI in the same individuals. When reconstructing brain responses to visual stimuli that differed by angular position, we found reliable localization to the appropriate retinotopic visual field quadrant by a minimum norm approach and by beamforming. Retinotopic map eccentricity in accordance with the fMRI map could not consistently be localized using an annular stimulus with any reconstruction method, but confining eccentricity stimuli to one visual field quadrant resulted in significant improvement with the minimum norm. These results inform the application of source analysis approaches for future MEG studies of the visual system, and indicate some current limits on localization accuracy of MEG signals. PMID:24904268

  13. Single-shot T2 mapping using overlapping-echo detachment planar imaging and a deep convolutional neural network.

    PubMed

    Cai, Congbo; Wang, Chao; Zeng, Yiqing; Cai, Shuhui; Liang, Dong; Wu, Yawen; Chen, Zhong; Ding, Xinghao; Zhong, Jianhui

    2018-04-24

    An end-to-end deep convolutional neural network (CNN) based on deep residual network (ResNet) was proposed to efficiently reconstruct reliable T 2 mapping from single-shot overlapping-echo detachment (OLED) planar imaging. The training dataset was obtained from simulations that were carried out on SPROM (Simulation with PRoduct Operator Matrix) software developed by our group. The relationship between the original OLED image containing two echo signals and the corresponding T 2 mapping was learned by ResNet training. After the ResNet was trained, it was applied to reconstruct the T 2 mapping from simulation and in vivo human brain data. Although the ResNet was trained entirely on simulated data, the trained network was generalized well to real human brain data. The results from simulation and in vivo human brain experiments show that the proposed method significantly outperforms the echo-detachment-based method. Reliable T 2 mapping with higher accuracy is achieved within 30 ms after the network has been trained, while the echo-detachment-based OLED reconstruction method took approximately 2 min. The proposed method will facilitate real-time dynamic and quantitative MR imaging via OLED sequence, and deep convolutional neural network has the potential to reconstruct maps from complex MRI sequences efficiently. © 2018 International Society for Magnetic Resonance in Medicine.

  14. Cognitive Navigation: Toward a Biological Basis for Instructional Design.

    ERIC Educational Resources Information Center

    Tripp, Steven

    2001-01-01

    Discusses cognitive navigation, cognitive maps and online learning, and the role of the hippocampus in navigation. Topics include brain research in animal and human studies; types of memory; human navigation, including land navigation and information navigation; instructional strategies; tree maps of curriculum structure; cognitive complexity; and…

  15. 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

  16. Brain Entropy Mapping Using fMRI

    PubMed Central

    Wang, Ze; Li, Yin; Childress, Anna Rose; Detre, John A.

    2014-01-01

    Entropy is an important trait for life as well as the human brain. Characterizing brain entropy (BEN) may provide an informative tool to assess brain states and brain functions. Yet little is known about the distribution and regional organization of BEN in normal brain. The purpose of this study was to examine the whole brain entropy patterns using a large cohort of normal subjects. A series of experiments were first performed to validate an approximate entropy measure regarding its sensitivity, specificity, and reliability using synthetic data and fMRI data. Resting state fMRI data from a large cohort of normal subjects (n = 1049) from multi-sites were then used to derive a 3-dimensional BEN map, showing a sharp low-high entropy contrast between the neocortex and the rest of brain. The spatial heterogeneity of resting BEN was further studied using a data-driven clustering method, and the entire brain was found to be organized into 7 hierarchical regional BEN networks that are consistent with known structural and functional brain parcellations. These findings suggest BEN mapping as a physiologically and functionally meaningful measure for studying brain functions. PMID:24657999

  17. Areas activated during naturalistic reading comprehension overlap topological visual, auditory, and somatotomotor maps.

    PubMed

    Sood, Mariam R; Sereno, Martin I

    2016-08-01

    Cortical mapping techniques using fMRI have been instrumental in identifying the boundaries of topological (neighbor-preserving) maps in early sensory areas. The presence of topological maps beyond early sensory areas raises the possibility that they might play a significant role in other cognitive systems, and that topological mapping might help to delineate areas involved in higher cognitive processes. In this study, we combine surface-based visual, auditory, and somatomotor mapping methods with a naturalistic reading comprehension task in the same group of subjects to provide a qualitative and quantitative assessment of the cortical overlap between sensory-motor maps in all major sensory modalities, and reading processing regions. Our results suggest that cortical activation during naturalistic reading comprehension overlaps more extensively with topological sensory-motor maps than has been heretofore appreciated. Reading activation in regions adjacent to occipital lobe and inferior parietal lobe almost completely overlaps visual maps, whereas a significant portion of frontal activation for reading in dorsolateral and ventral prefrontal cortex overlaps both visual and auditory maps. Even classical language regions in superior temporal cortex are partially overlapped by topological visual and auditory maps. By contrast, the main overlap with somatomotor maps is restricted to a small region on the anterior bank of the central sulcus near the border between the face and hand representations of M-I. Hum Brain Mapp 37:2784-2810, 2016. © 2016 The Authors Human Brain Mapping Published by Wiley Periodicals, Inc. © 2016 The Authors Human Brain Mapping Published by Wiley Periodicals, Inc.

  18. Background field removal technique based on non-regularized variable kernels sophisticated harmonic artifact reduction for phase data for quantitative susceptibility mapping.

    PubMed

    Kan, Hirohito; Arai, Nobuyuki; Takizawa, Masahiro; Omori, Kazuyoshi; Kasai, Harumasa; Kunitomo, Hiroshi; Hirose, Yasujiro; Shibamoto, Yuta

    2018-06-11

    We developed a non-regularized, variable kernel, sophisticated harmonic artifact reduction for phase data (NR-VSHARP) method to accurately estimate local tissue fields without regularization for quantitative susceptibility mapping (QSM). We then used a digital brain phantom to evaluate the accuracy of the NR-VSHARP method, and compared it with the VSHARP and iterative spherical mean value (iSMV) methods through in vivo human brain experiments. Our proposed NR-VSHARP method, which uses variable spherical mean value (SMV) kernels, minimizes L2 norms only within the volume of interest to reduce phase errors and save cortical information without regularization. In a numerical phantom study, relative local field and susceptibility map errors were determined using NR-VSHARP, VSHARP, and iSMV. Additionally, various background field elimination methods were used to image the human brain. In a numerical phantom study, the use of NR-VSHARP considerably reduced the relative local field and susceptibility map errors throughout a digital whole brain phantom, compared with VSHARP and iSMV. In the in vivo experiment, the NR-VSHARP-estimated local field could sufficiently achieve minimal boundary losses and phase error suppression throughout the brain. Moreover, the susceptibility map generated using NR-VSHARP minimized the occurrence of streaking artifacts caused by insufficient background field removal. Our proposed NR-VSHARP method yields minimal boundary losses and highly precise phase data. Our results suggest that this technique may facilitate high-quality QSM. Copyright © 2017. Published by Elsevier Inc.

  19. 78 FR 14797 - Findings of Research Misconduct

    Federal Register 2010, 2011, 2012, 2013, 2014

    2013-03-07

    ...) ``Incentive Induced Changes in Neural Patterns During Task-Switching.'' Organization for Human Brain Mapping... categories in Figure 9. 3. Falsified data in J Neurosci. 2010 and mislabeled brain images to show that... brain regions, behavioral performance, and trial outcomes. Specifically, Respondent modified the data so...

  20. 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.

  1. Cytoarchitectonic identification and probabilistic mapping of two distinct areas within the anterior ventral bank of the human intraparietal sulcus

    PubMed Central

    Choi, Hi-Jae; Zilles, Karl; Mohlberg, Hartmut; Schleicher, Axel; Fink, Gereon R.; Armstrong, Este; Amunts, Katrin

    2008-01-01

    Anatomical studies in the macaque cortex and functional imaging studies in humans have demonstrated the existence of different cortical areas within the IntraParietal Sulcus (IPS). Such functional segregation, however, does not correlate with presently available architectonic maps of the human brain. This is particularly true for the classical Brodmann map, which is still widely used as an anatomical reference in functional imaging studies. The aim of this cytoarchitectonic mapping study was to use previously defined algorithms to determine whether consistent regions and borders can be found within the cortex of the anterior IPS in a population of ten postmortem human brains. Two areas, the human IntraParietal area 1 (hIP1) and the human IntraParietal area 2 (hIP2), were delineated in serial histological sections of the anterior, lateral bank of the human IPS. The region hIP1 is located posterior and medial to hIP2, and the former is always within the depths of the IPS. The latter, on the other hand, sometimes reaches the free surface of the superior parietal lobule. The delineations were registered to standard reference space, and probabilistic maps were calculated, thereby quantifying the intersubject variability in location and extent of both areas. In the future, they can be a tool in analyzing structure – function relationships and a basis for determining degrees of homology in the IPS among anthropoid primates. We conclude that the human intraparietal sulcus has a finer grained parcellation than shown in Brodmann’s map. PMID:16432904

  2. Critical perspectives on causality and inference in brain networks: Allusions, illusions, solutions?. Comment on: "Foundational perspectives on causality in large-scale brain networks" by M. Mannino and S.L. Bressler

    NASA Astrophysics Data System (ADS)

    Diwadkar, Vaibhav A.

    2015-12-01

    The human brain is an impossibly difficult cartographic landscape to map out. Within it's convoluted and labyrinthine structure is folded a million years of phylogeny, somehow expressed in the ontogeny of the specific organism; an ontogeny that conceals idiosyncratic effects of countless genes, and then the (perhaps) countably infinite effects of processes of the organism's lifespan subsequently resulting in remarkable heterogeneity [1,2]. The physical brain itself is therefore a nearly un-decodable ;time machine; motivating more questions than frameworks for answering those questions: Why has evolution endowed it with the general structure that is possesses [3]; Is there regularity in macroscopic metrics of structure across species [4]; What are the most meaningful structural units in the brain: molecules, neurons, cortical columns or cortical maps [5]? Remarkably, understanding the intricacies of structure is perhaps not even the most difficult aspect of understanding the human brain. In fact, and as recently argued, a central issue lies in resolving the dialectic between structure and function: how does dynamic function arises from static (at least at the time scales at which human brain function is experimentally studied) brain structures [6]? In other words, if the mind is the brain ;in action;, how does it arise?

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

    PubMed

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

    2018-03-01

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

  4. [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".

  5. Towards Ultra-High Resolution Fibre Tract Mapping of the Human Brain – Registration of Polarised Light Images and Reorientation of Fibre Vectors

    PubMed Central

    Palm, Christoph; Axer, Markus; Gräßel, David; Dammers, Jürgen; Lindemeyer, Johannes; Zilles, Karl; Pietrzyk, Uwe; Amunts, Katrin

    2009-01-01

    Polarised light imaging (PLI) utilises the birefringence of the myelin sheaths in order to visualise the orientation of nerve fibres in microtome sections of adult human post-mortem brains at ultra-high spatial resolution. The preparation of post-mortem brains for PLI involves fixation, freezing and cutting into 100-μm-thick sections. Hence, geometrical distortions of histological sections are inevitable and have to be removed for 3D reconstruction and subsequent fibre tracking. We here present a processing pipeline for 3D reconstruction of these sections using PLI derived multimodal images of post-mortem brains. Blockface images of the brains were obtained during cutting; they serve as reference data for alignment and elimination of distortion artefacts. In addition to the spatial image transformation, fibre orientation vectors were reoriented using the transformation fields, which consider both affine and subsequent non-linear registration. The application of this registration and reorientation approach results in a smooth fibre vector field, which reflects brain morphology. PLI combined with 3D reconstruction and fibre tracking is a powerful tool for human brain mapping. It can also serve as an independent method for evaluating in vivo fibre tractography. PMID:20461231

  6. Top-Down Predictions in the Cognitive Brain

    ERIC Educational Resources Information Center

    Kveraga, Kestutis; Ghuman, Avniel S.; Bar, Moshe

    2007-01-01

    The human brain is not a passive organ simply waiting to be activated by external stimuli. Instead, we propose that the brain continuously employs memory of past experiences to interpret sensory information and predict the immediately relevant future. The basic elements of this proposal include analogical mapping, associative representations and…

  7. Neonatal brain resting-state functional connectivity imaging modalities.

    PubMed

    Mohammadi-Nejad, Ali-Reza; Mahmoudzadeh, Mahdi; Hassanpour, Mahlegha S; Wallois, Fabrice; Muzik, Otto; Papadelis, Christos; Hansen, Anne; Soltanian-Zadeh, Hamid; Gelovani, Juri; Nasiriavanaki, Mohammadreza

    2018-06-01

    Infancy is the most critical period in human brain development. Studies demonstrate that subtle brain abnormalities during this state of life may greatly affect the developmental processes of the newborn infants. One of the rapidly developing methods for early characterization of abnormal brain development is functional connectivity of the brain at rest. While the majority of resting-state studies have been conducted using magnetic resonance imaging (MRI), there is clear evidence that resting-state functional connectivity (rs-FC) can also be evaluated using other imaging modalities. The aim of this review is to compare the advantages and limitations of different modalities used for the mapping of infants' brain functional connectivity at rest. In addition, we introduce photoacoustic tomography, a novel functional neuroimaging modality, as a complementary modality for functional mapping of infants' brain.

  8. Noninvasive near-infrared topography of human brain activity using intensity modulation spectroscopy

    NASA Astrophysics Data System (ADS)

    Yamashita, Yuichi; Maki, Atsushi; Ito, Yoshitoshi; Watanabe, Eiju; Mayanagi, Yoshiaki; Koizumi, Hideaki

    1996-04-01

    We describe the functional topography of human brain activity due to motor stimulation by using near-infrared spectroscopy. Finger motion by each hand was used as the motor stimulation, and activity in the left fronto-central region of the brain was measured. A greater change in oxyhemoglobin concentration due to brain activity during the stimulation was obtained for the right hand than for the left hand. Localization of the activity was obtained by topographically mapping the measured changes for ten positions within the region.

  9. Probabilistic map of critical functional regions of the human cerebral cortex: Broca's area revisited.

    PubMed

    Tate, Matthew C; Herbet, Guillaume; Moritz-Gasser, Sylvie; Tate, Joseph E; Duffau, Hugues

    2014-10-01

    The organization of basic functions of the human brain, particularly in the right hemisphere, remains poorly understood. Recent advances in functional neuroimaging have improved our understanding of cortical organization but do not allow for direct interrogation or determination of essential (versus participatory) cortical regions. Direct cortical stimulation represents a unique opportunity to provide novel insights into the functional distribution of critical epicentres. Direct cortical stimulation (bipolar, 60 Hz, 1-ms pulse) was performed in 165 consecutive patients undergoing awake mapping for resection of low-grade gliomas. Tasks included motor, sensory, counting, and picture naming. Stimulation sites eliciting positive (sensory/motor) or negative (speech arrest, dysarthria, anomia, phonological and semantic paraphasias) findings were recorded and mapped onto a standard Montreal Neurological Institute brain atlas. Montreal Neurological Institute-space functional data were subjected to cluster analysis algorithms (K-means, partition around medioids, hierarchical Ward) to elucidate crucial network epicentres. Sensorimotor function was observed in the pre/post-central gyri as expected. Articulation epicentres were also found within the pre/post-central gyri. However, speech arrest localized to ventral premotor cortex, not the classical Broca's area. Anomia/paraphasia data demonstrated foci not only within classical Wernicke's area but also within the middle and inferior frontal gyri. We report the first bilateral probabilistic map for crucial cortical epicentres of human brain functions in the right and left hemispheres, including sensory, motor, and language (speech, articulation, phonology and semantics). These data challenge classical theories of brain organization (e.g. Broca's area as speech output region) and provide a distributed framework for future studies of neural networks. © The Author (2014). Published by Oxford University Press on behalf of the Guarantors of Brain. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

  10. Passive language mapping combining real-time oscillation analysis with cortico-cortical evoked potentials for awake craniotomy.

    PubMed

    Tamura, Yukie; Ogawa, Hiroshi; Kapeller, Christoph; Prueckl, Robert; Takeuchi, Fumiya; Anei, Ryogo; Ritaccio, Anthony; Guger, Christoph; Kamada, Kyousuke

    2016-12-01

    OBJECTIVE Electrocortical stimulation (ECS) is the gold standard for functional brain mapping; however, precise functional mapping is still difficult in patients with language deficits. High gamma activity (HGA) between 80 and 140 Hz on electrocorticography is assumed to reflect localized cortical processing, whereas the cortico-cortical evoked potential (CCEP) can reflect bidirectional responses evoked by monophasic pulse stimuli to the language cortices when there is no patient cooperation. The authors propose the use of "passive" mapping by combining HGA mapping and CCEP recording without active tasks during conscious resections of brain tumors. METHODS Five patients, each with an intraaxial tumor in their dominant hemisphere, underwent conscious resection of their lesion with passive mapping. The authors performed functional localization for the receptive language area, using real-time HGA mapping, by listening passively to linguistic sounds. Furthermore, single electrical pulses were delivered to the identified receptive temporal language area to detect CCEPs in the frontal lobe. All mapping results were validated by ECS, and the sensitivity and specificity were evaluated. RESULTS Linguistic HGA mapping quickly identified the language area in the temporal lobe. Electrical stimulation by linguistic HGA mapping to the identified temporal receptive language area evoked CCEPs on the frontal lobe. The combination of linguistic HGA and frontal CCEPs needed no patient cooperation or effort. In this small case series, the sensitivity and specificity were 93.8% and 89%, respectively. CONCLUSIONS The described technique allows for simple and quick functional brain mapping with higher sensitivity and specificity than ECS mapping. The authors believe that this could improve the reliability of functional brain mapping and facilitate rational and objective operations. Passive mapping also sheds light on the underlying physiological mechanisms of language in the human brain.

  11. 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.

  12. Mapping Functional Brain Development: Building a Social Brain through Interactive Specialization

    ERIC Educational Resources Information Center

    Johnson, Mark H.; Grossmann, Tobias; Kadosh, Kathrin Cohen

    2009-01-01

    The authors review a viewpoint on human functional brain development, interactive specialization (IS), and its application to the emerging network of cortical regions referred to as the "social brain." They advance the IS view in 2 new ways. First, they extend IS into a domain to which it has not previously been applied--the emergence of social…

  13. A volumetric conformal mapping approach for clustering white matter fibers in the brain

    PubMed Central

    Gupta, Vikash; Prasad, Gautam; Thompson, Paul

    2017-01-01

    The human brain may be considered as a genus-0 shape, topologically equivalent to a sphere. Various methods have been used in the past to transform the brain surface to that of a sphere using harmonic energy minimization methods used for cortical surface matching. However, very few methods have studied volumetric parameterization of the brain using a spherical embedding. Volumetric parameterization is typically used for complicated geometric problems like shape matching, morphing and isogeometric analysis. Using conformal mapping techniques, we can establish a bijective mapping between the brain and the topologically equivalent sphere. Our hypothesis is that shape analysis problems are simplified when the shape is defined in an intrinsic coordinate system. Our goal is to establish such a coordinate system for the brain. The efficacy of the method is demonstrated with a white matter clustering problem. Initial results show promise for future investigation in these parameterization technique and its application to other problems related to computational anatomy like registration and segmentation. PMID:29177252

  14. Longitudinal atlas for normative human brain development and aging over the lifespan using quantitative susceptibility mapping.

    PubMed

    Zhang, Yuyao; Wei, Hongjiang; Cronin, Matthew J; He, Naying; Yan, Fuhua; Liu, Chunlei

    2018-05-01

    Longitudinal brain atlases play an important role in the study of human brain development and cognition. Existing atlases are mainly based on anatomical features derived from T1-and T2-weighted MRI. A 4D developmental quantitative susceptibility mapping (QSM) atlas may facilitate the estimation of age-related iron changes in deep gray matter nuclei and myelin changes in white matter. To this end, group-wise co-registered QSM templates were generated over various age intervals from age 1-83 years old. Registration was achieved by combining both T1-weighted and QSM images. Based on the proposed template, we created an accurate deep gray matter nuclei parcellation map (DGM map). Notably, we segmented thalamus into 5 sub-regions, i.e. the anterior nuclei, the median nuclei, the lateral nuclei, the pulvinar and the internal medullary lamina. Furthermore, we built a "whole brain QSM parcellation map" by combining existing cortical parcellation and white-matter atlases with the proposed DGM map. Based on the proposed QSM atlas, the segmentation accuracy of iron-rich nuclei using QSM is significantly improved, especially for children and adolescent subjects. The age-related progression of magnetic susceptibility in each of the deep gray matter nuclei, the hippocampus, and the amygdala was estimated. Our automated atlas-based analysis provided a systematic confirmation of previous findings on susceptibility progression with age resulting from manual ROI drawings in deep gray matter nuclei. The susceptibility development in the hippocampus and the amygdala follow an iron accumulation model; while in the thalamus sub-regions, the susceptibility development exhibits a variety of trends. It is envisioned that the newly developed 4D QSM atlas will serve as a template for studying brain iron deposition and myelination/demyelination in both normal aging and various brain diseases. Copyright © 2018 Elsevier Inc. All rights reserved.

  15. Effects of spatial variation of skull and cerebrospinal fluid layers on optical mapping of brain activities

    NASA Astrophysics Data System (ADS)

    Wang, Shuping; Shibahara, Nanae; Kuramashi, Daishi; Okawa, Shinpei; Kakuta, Naoto; Okada, Eiji; Maki, Atsushi; Yamada, Yukio

    2010-07-01

    In order to investigate the effects of anatomical variation in human heads on the optical mapping of brain activity, we perform simulations of optical mapping by solving the photon diffusion equation for layered-models simulating human heads using the finite element method (FEM). Particularly, the effects of the spatial variations in the thicknesses of the skull and cerebrospinal fluid (CSF) layers on mapping images are investigated. Mapping images of single active regions in the gray matter layer are affected by the spatial variations in the skull and CSF layer thicknesses, although the effects are smaller than those of the positions of the active region relative to the data points. The increase in the skull thickness decreases the sensitivity of the images to active regions, while the increase in the CSF layer thickness increases the sensitivity in general. The images of multiple active regions are also influenced by their positions relative to the data points and by their depths from the skin surface.

  16. 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.

  17. Computer-assisted mapping of immunoreactive mammalian gonadotropin-releasing hormone in adult human basal forebrain and amygdala.

    PubMed

    Stopa, E G; Koh, E T; Svendsen, C N; Rogers, W T; Schwaber, J S; King, J C

    1991-06-01

    Immunocytochemistry performed on 80-microns unembedded tissue sections was used to study the localization of GnRH-containing neurons and fibers in the basal forebrain and amygdala of six adult (four male, two female) human brains. Sections from one of the female brains were subjected to computer-assisted microscopic mapping to generate a three-dimensional analysis of immunoreactive structures. In all six brains examined, cell bodies were concentrated in the preoptic area and basal hypothalamus, but were also evident in the septal region, anterior olfactory area, and cortical and medial amygdaloid nuclei. GnRH-containing fibers were observed within the hypothalamus (predominantly infundibular region and preoptic area), septum, stria terminalis, ventral pallidum, dorsomedial thalamus, olfactory stria, and anterior olfactory area. Many fibers could also be seen coursing along the base of the brain between the hypothalamus and cortical and medial amygdaloid nuclei. The localization of GnRH-containing cells and fibers in several of these areas represents new observations in the human brain and suggests a role for the amygdaloid complex in the regulation of gonadotropin secretion. The comprehensive view provided by these data may be useful in the clinical application of novel transplantation strategies.

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

    PubMed Central

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

    2018-01-01

    Abstract A century of research in human brain parcellation has demonstrated that different brain areas are associated with functional tasks. New neuroscientist perspectives to achieve the parcellation of the human brain have been developed to know the brain areas activation and its relationship with different stimuli. This descriptive study aimed to compare brain regions activation by specific tactile input (STI) stimuli according to the Vojta protocol (STI-group) to a non-STI stimulation (non-STI-group). An exploratory functional magnetic resonance imaging (fMRI) study was performed. The 2 groups of participants were passively stimulated by an expert physical therapist using the same paradigm structure, although differing in the place of stimulation. The stimulation was presented to participants using a block design in all cases. A sample of 16 healthy participants, 5 men and 11 women, with mean age 31.31 ± 8.13 years was recruited. Indeed, 12 participants were allocated in the STI-group and 4 participants in the non-STI-group. fMRI was used to map the human brain in vivo while these tactile stimuli were being applied. Data were analyzed using a general linear model in SPM12 implemented in MATLAB. Differences between groups showed a greater activation in the right cortical areas (temporal and frontal lobes), subcortical regions (thalamus, brainstem, and basal nuclei), and in the cerebellum (anterior lobe). STI-group had specific difference brain activation areas, such as the ipsilateral putamen. Future studies should study clinical implications in neurorehabilitation patients. PMID:29595683

  19. Event-related functional MRI: Past, present, and future

    PubMed Central

    Rosen, Bruce R.; Buckner, Randy L.; Dale, Anders M.

    1998-01-01

    The past two decades have seen an enormous growth in the field of human brain mapping. Investigators have extensively exploited techniques such as positron emission tomography and MRI to map patterns of brain activity based on changes in cerebral hemodynamics. However, until recently, most studies have investigated equilibrium changes in blood flow measured over time periods upward of 1 min. The advent of high-speed MRI methods, capable of imaging the entire brain with a temporal resolution of a few seconds, allows for brain mapping based on more transient aspects of the hemodynamic response. Today it is now possible to map changes in cerebrovascular parameters essentially in real time, conferring the ability to observe changes in brain state that occur over time periods of seconds. Furthermore, because robust hemodynamic alterations are detectable after neuronal stimuli lasting only a few tens of milliseconds, a new class of task paradigms designed to measure regional responses to single sensory or cognitive events can now be studied. Such “event related” functional MRI should provide for fundamentally new ways to interrogate brain function, and allow for the direct comparison and ultimately integration of data acquired by using more traditional behavioral and electrophysiological methods. PMID:9448240

  20. In Vivo Fiber-Optic Raman Mapping Of Metastases In Mouse Brains

    NASA Astrophysics Data System (ADS)

    Stelling, A.; Kirsch, M.; Steiner, G.; Krafft, C.; Schackert, G.; Salzer, R.

    2010-08-01

    Vibrational spectroscopy, in particular Raman spectroscopy, has potential applications in the field of in vivo diagnostics. Raman and FT-IR spectroscopy analyze the complete biochemical information at any given pixel within the visual field. Here we demonstrate the feasibility of performing Raman spectroscopic measurements on living mice brains using a fiber-optic probe with a nominal spatial resolution of 60 μm. The objectives of this study were to 1) evaluate preclinical models, namely murine brain slices containing experimental tumors, 2) optimize the preparation of pristine brain tissue to obtain reference information, to 3) optimize the conditions for introducing a fiber-optic probe to acquire Raman maps in vivo, and 4) to transfer results obtained from human brain tumors to an animal model. Disseminated brain metastases of malignant melanomas were induced by injecting tumor cells into the carotid artery of mice. The procedure mimicked hematogenous tumor spread in one brain hemisphere while the other hemisphere remained tumor free. Three series of sections were prepared consecutively from whole mouse brains: pristine, 2-mm thick sections for Raman mapping and dried, thin sections for FT-IR imaging, hematoxylin and eosin-stained thin sections for histopathological assessment. Raman maps were collected serially using a spectrometer coupled to a fiber-optic probe. FT-IR images were recorded using a spectrometer with a multi-channel detector. The FT-IR images and the Raman maps were evaluated by multivariate data analysis. The results obtained from the thin section studies were employed to guide measurements of murine brains in vivo. Raman maps with an acquisition time of over an hour could be performed on the living animals. No damage to the tissue was observed.

  1. Topographic brain mapping of emotion-related hemisphere asymmetries.

    PubMed

    Roschmann, R; Wittling, W

    1992-03-01

    The study used topographic brain mapping of visual evoked potentials to investigate emotion-related hemisphere asymmetries. The stimulus material consisted of color photographs of human faces, grouped into two emotion-related categories: normal faces (neutral stimuli) and faces deformed by dermatological diseases (emotional stimuli). The pictures were presented tachistoscopically to 20 adult right-handed subjects. Brain activity was recorded by 30 EEG electrodes with linked ears as reference. The waveforms were averaged separately with respect to each of the two stimulus conditions. Statistical analysis by means of significance probability mapping revealed significant differences between stimulus conditions for two periods of time, indicating right hemisphere superiority in emotion-related processing. The results are discussed in terms of a 2-stage-model of emotional processing in the cerebral hemispheres.

  2. Intraoperative intrinsic optical imaging of human somatosensory cortex during neurosurgical operations.

    PubMed

    Sato, Katsushige; Nariai, Tadashi; Momose-Sato, Yoko; Kamino, Kohtaro

    2017-07-01

    Intrinsic optical imaging as developed by Grinvald et al. is a powerful technique for monitoring neural function in the in vivo central nervous system. The advent of this dye-free imaging has also enabled us to monitor human brain function during neurosurgical operations. We briefly describe our own experience in functional mapping of the human somatosensory cortex, carried out using intraoperative optical imaging. The maps obtained demonstrate new additional evidence of a hierarchy for sensory response patterns in the human primary somatosensory cortex.

  3. Correspondence of the brain's functional architecture during activation and rest.

    PubMed

    Smith, Stephen M; Fox, Peter T; Miller, Karla L; Glahn, David C; Fox, P Mickle; Mackay, Clare E; Filippini, Nicola; Watkins, Kate E; Toro, Roberto; Laird, Angela R; Beckmann, Christian F

    2009-08-04

    Neural connections, providing the substrate for functional networks, exist whether or not they are functionally active at any given moment. However, it is not known to what extent brain regions are continuously interacting when the brain is "at rest." In this work, we identify the major explicit activation networks by carrying out an image-based activation network analysis of thousands of separate activation maps derived from the BrainMap database of functional imaging studies, involving nearly 30,000 human subjects. Independently, we extract the major covarying networks in the resting brain, as imaged with functional magnetic resonance imaging in 36 subjects at rest. The sets of major brain networks, and their decompositions into subnetworks, show close correspondence between the independent analyses of resting and activation brain dynamics. We conclude that the full repertoire of functional networks utilized by the brain in action is continuously and dynamically "active" even when at "rest."

  4. Mapping and reconstruction of domoic acid-induced neurodegeneration in the mouse brain.

    PubMed

    Colman, J R; Nowocin, K J; Switzer, R C; Trusk, T C; Ramsdell, J S

    2005-01-01

    Domoic acid, a potent neurotoxin and glutamate analog produced by certain species of the marine diatom Pseudonitzschia, is responsible for several human and wildlife intoxication events. The toxin characteristically damages the hippocampus in exposed humans, rodents, and marine mammals. Histochemical studies have identified this, and other regions of neurodegeneration, though none have sought to map all brain regions affected by domoic acid. In this study, mice exposed (i.p.) to 4 mg/kg domoic acid for 72 h exhibited behavioral and pathological signs of neurotoxicity. Brains were fixed by intracardial perfusion and processed for histochemical analysis. Serial coronal sections (50 microm) were stained using the degeneration-sensitive cupric silver staining method of DeOlmos. Degenerated axons, terminals, and cell bodies, which stained black, were identified and the areas of degeneration were mapped onto Paxinos mouse atlas brain plates using Adobe Illustrator CS. The plates were then combined to reconstruct a 3-dimensional image of domoic acid-induced neurodegeneration using Amira 3.1 software. Affected regions included the olfactory bulb, septal area, and limbic system. These findings are consistent with behavioral and pathological studies demonstrating the effects of domoic acid on cognitive function and neurodegeneration in rodents.

  5. 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.

  6. The study of the wonderful: the first topographical mapping of vision in the brain.

    PubMed

    Fishman, Ronald S

    2008-12-01

    The conception by René Descartes of the human brain, notorious as it is for placing the soul or mind in the pineal gland, had yet within it the basic idea of the brain as a highly organized mechanism with topographical sensory mapping and different functions localized in specific areas. Descartes was directly led to this idea by his appreciation of what the retinal image conceived by Johannes Kepler implied, not only for the nature of vision, but for the operation of the brain in general. The linkage between Kepler and Descartes is not widely appreciated but is one of the best examples of synergism in the history of science.

  7. Linking brain, mind and behavior.

    PubMed

    Makeig, Scott; Gramann, Klaus; Jung, Tzyy-Ping; Sejnowski, Terrence J; Poizner, Howard

    2009-08-01

    Cortical brain areas and dynamics evolved to organize motor behavior in our three-dimensional environment also support more general human cognitive processes. Yet traditional brain imaging paradigms typically allow and record only minimal participant behavior, then reduce the recorded data to single map features of averaged responses. To more fully investigate the complex links between distributed brain dynamics and motivated natural behavior, we propose the development of wearable mobile brain/body imaging (MoBI) systems that continuously capture the wearer's high-density electrical brain and muscle signals, three-dimensional body movements, audiovisual scene and point of regard, plus new data-driven analysis methods to model their interrelationships. The new imaging modality should allow new insights into how spatially distributed brain dynamics support natural human cognition and agency.

  8. Unbalanced neuronal circuits in addiction.

    PubMed

    Volkow, Nora D; Wang, Gen-Jack; Tomasi, Dardo; Baler, Ruben D

    2013-08-01

    Through sequential waves of drug-induced neurochemical stimulation, addiction co-opts the brain's neuronal circuits that mediate reward, motivation to behavioral inflexibility and a severe disruption of self-control and compulsive drug intake. Brain imaging technologies have allowed neuroscientists to map out the neural landscape of addiction in the human brain and to understand how drugs modify it. Published by Elsevier Ltd.

  9. Pig brain stereotaxic standard space: mapping of cerebral blood flow normative values and effect of MPTP-lesioning.

    PubMed

    Andersen, Flemming; Watanabe, Hideaki; Bjarkam, Carsten; Danielsen, Erik H; Cumming, Paul

    2005-07-15

    The analysis of physiological processes in brain by position emission tomography (PET) is facilitated when images are spatially normalized to a standard coordinate system. Thus, PET activation studies of human brain frequently employ the common stereotaxic coordinates of Talairach. We have developed an analogous stereotaxic coordinate system for the brain of the Gottingen miniature pig, based on automatic co-registration of magnetic resonance (MR) images obtained in 22 male pigs. The origin of the pig brain stereotaxic space (0, 0, 0) was arbitrarily placed in the centroid of the pineal gland as identified on the average MRI template. The orthogonal planes were imposed using the line between stereotaxic zero and the optic chiasm. A series of mean MR images in the coronal, sagittal and horizontal planes were generated. To test the utility of the common coordinate system for functional imaging studies of minipig brain, we calculated cerebral blood flow (CBF) maps from normal minipigs and from minipigs with a syndrome of parkisonism induced by 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-poisoning. These maps were transformed from the native space into the common stereotaxic space. After global normalization of these maps, an undirected search for differences between the groups was then performed using statistical parametric mapping. Using this method, we detected a statistically significant focal increase in CBF in the left cerebellum of the MPTP-lesioned group. We expect the present approach to be of general use in the statistical parametric mapping of CBF and other physiological parameters in living pig brain.

  10. 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.

  11. High-field fMRI unveils orientation columns in humans.

    PubMed

    Yacoub, Essa; Harel, Noam; Ugurbil, Kâmil

    2008-07-29

    Functional (f)MRI has revolutionized the field of human brain research. fMRI can noninvasively map the spatial architecture of brain function via localized increases in blood flow after sensory or cognitive stimulation. Recent advances in fMRI have led to enhanced sensitivity and spatial accuracy of the measured signals, indicating the possibility of detecting small neuronal ensembles that constitute fundamental computational units in the brain, such as cortical columns. Orientation columns in visual cortex are perhaps the best known example of such a functional organization in the brain. They cannot be discerned via anatomical characteristics, as with ocular dominance columns. Instead, the elucidation of their organization requires functional imaging methods. However, because of insufficient sensitivity, spatial accuracy, and image resolution of the available mapping techniques, thus far, they have not been detected in humans. Here, we demonstrate, by using high-field (7-T) fMRI, the existence and spatial features of orientation- selective columns in humans. Striking similarities were found with the known spatial features of these columns in monkeys. In addition, we found that a larger number of orientation columns are devoted to processing orientations around 90 degrees (vertical stimuli with horizontal motion), whereas relatively similar fMRI signal changes were observed across any given active column. With the current proliferation of high-field MRI systems and constant evolution of fMRI techniques, this study heralds the exciting prospect of exploring unmapped and/or unknown columnar level functional organizations in the human brain.

  12. Control-display mapping in brain-computer interfaces.

    PubMed

    Thurlings, Marieke E; van Erp, Jan B F; Brouwer, Anne-Marie; Blankertz, Benjamin; Werkhoven, Peter

    2012-01-01

    Event-related potential (ERP) based brain-computer interfaces (BCIs) employ differences in brain responses to attended and ignored stimuli. When using a tactile ERP-BCI for navigation, mapping is required between navigation directions on a visual display and unambiguously corresponding tactile stimuli (tactors) from a tactile control device: control-display mapping (CDM). We investigated the effect of congruent (both display and control horizontal or both vertical) and incongruent (vertical display, horizontal control) CDMs on task performance, the ERP and potential BCI performance. Ten participants attended to a target (determined via CDM), in a stream of sequentially vibrating tactors. We show that congruent CDM yields best task performance, enhanced the P300 and results in increased estimated BCI performance. This suggests a reduced availability of attentional resources when operating an ERP-BCI with incongruent CDM. Additionally, we found an enhanced N2 for incongruent CDM, which indicates a conflict between visual display and tactile control orientations. Incongruency in control-display mapping reduces task performance. In this study, brain responses, task and system performance are related to (in)congruent mapping of command options and the corresponding stimuli in a brain-computer interface (BCI). Directional congruency reduces task errors, increases available attentional resources, improves BCI performance and thus facilitates human-computer interaction.

  13. 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.

  14. 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.

  15. Comparison of NREM sleep and intravenous sedation through local information processing and whole brain network to explore the mechanism of general anesthesia.

    PubMed

    Li, Yun; Wang, Shengpei; Pan, Chuxiong; Xue, Fushan; Xian, Junfang; Huang, Yaqi; Wang, Xiaoyi; Li, Tianzuo; He, Huiguang

    2018-01-01

    The mechanism of general anesthesia (GA) has been explored for hundreds of years, but unclear. Previous studies indicated a possible correlation between NREM sleep and GA. The purpose of this study is to compare them by in vivo human brain function to probe the neuromechanism of consciousness, so as to find out a clue to GA mechanism. 24 healthy participants were equally assigned to sleep or propofol sedation group by sleeping ability. EEG and Ramsay Sedation Scale were applied to determine sleep stage and sedation depth respectively. Resting-state functional magnetic resonance imaging (RS-fMRI) was acquired at each status. Regional homogeneity (ReHo) and seed-based whole brain functional connectivity maps (WB-FC maps) were compared. During sleep, ReHo primarily weakened on frontal lobe (especially preoptic area), but strengthened on brainstem. While during sedation, ReHo changed in various brain areas, including cingulate, precuneus, thalamus and cerebellum. Cingulate, fusiform and insula were concomitance of sleep and sedation. Comparing to sleep, FCs between the cortex and subcortical centers (centralized in cerebellum) were significantly attenuated under sedation. As sedation deepening, cerebellum-based FC maps were diminished, while thalamus- and brainstem-based FC maps were increased. There're huge distinctions in human brain function between sleep and GA. Sleep mainly rely on brainstem and frontal lobe function, while sedation is prone to affect widespread functional network. The most significant differences exist in the precuneus and cingulate, which may play important roles in mechanisms of inducing unconciousness by anesthetics. Institutional Review Board (IRB) ChiCTR-IOC-15007454.

  16. 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

  17. 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.

  18. An anatomical and functional topography of human auditory cortical areas

    PubMed Central

    Moerel, Michelle; De Martino, Federico; Formisano, Elia

    2014-01-01

    While advances in magnetic resonance imaging (MRI) throughout the last decades have enabled the detailed anatomical and functional inspection of the human brain non-invasively, to date there is no consensus regarding the precise subdivision and topography of the areas forming the human auditory cortex. Here, we propose a topography of the human auditory areas based on insights on the anatomical and functional properties of human auditory areas as revealed by studies of cyto- and myelo-architecture and fMRI investigations at ultra-high magnetic field (7 Tesla). Importantly, we illustrate that—whereas a group-based approach to analyze functional (tonotopic) maps is appropriate to highlight the main tonotopic axis—the examination of tonotopic maps at single subject level is required to detail the topography of primary and non-primary areas that may be more variable across subjects. Furthermore, we show that considering multiple maps indicative of anatomical (i.e., myelination) as well as of functional properties (e.g., broadness of frequency tuning) is helpful in identifying auditory cortical areas in individual human brains. We propose and discuss a topography of areas that is consistent with old and recent anatomical post-mortem characterizations of the human auditory cortex and that may serve as a working model for neuroscience studies of auditory functions. PMID:25120426

  19. Mapping the zebrafish brain methylome using reduced representation bisulfite sequencing

    PubMed Central

    Chatterjee, Aniruddha; Ozaki, Yuichi; Stockwell, Peter A; Horsfield, Julia A; Morison, Ian M; Nakagawa, Shinichi

    2013-01-01

    Reduced representation bisulfite sequencing (RRBS) has been used to profile DNA methylation patterns in mammalian genomes such as human, mouse and rat. The methylome of the zebrafish, an important animal model, has not yet been characterized at base-pair resolution using RRBS. Therefore, we evaluated the technique of RRBS in this model organism by generating four single-nucleotide resolution DNA methylomes of adult zebrafish brain. We performed several simulations to show the distribution of fragments and enrichment of CpGs in different in silico reduced representation genomes of zebrafish. Four RRBS brain libraries generated 98 million sequenced reads and had higher frequencies of multiple mapping than equivalent human RRBS libraries. The zebrafish methylome indicates there is higher global DNA methylation in the zebrafish genome compared with its equivalent human methylome. This observation was confirmed by RRBS of zebrafish liver. High coverage CpG dinucleotides are enriched in CpG island shores more than in the CpG island core. We found that 45% of the mapped CpGs reside in gene bodies, and 7% in gene promoters. This analysis provides a roadmap for generating reproducible base-pair level methylomes for zebrafish using RRBS and our results provide the first evidence that RRBS is a suitable technique for global methylation analysis in zebrafish. PMID:23975027

  20. Neural correlates of economic game playing.

    PubMed

    Krueger, Frank; Grafman, Jordan; McCabe, Kevin

    2008-12-12

    The theory of games provides a mathematical formalization of strategic choices, which have been studied in both economics and neuroscience, and more recently has become the focus of neuroeconomics experiments with human and non-human actors. This paper reviews the results from a number of game experiments that establish a unitary system for forming subjective expected utility maps in the brain, and acting on these maps to produce choices. Social situations require the brain to build an understanding of the other person using neuronal mechanisms that share affective and intentional mental states. These systems allow subjects to better predict other players' choices, and allow them to modify their subjective utility maps to value pro-social strategies. New results for a trust game are presented, which show that the trust relationship includes systems common to both trusting and trustworthy behaviour, but they also show that the relative temporal positions of first and second players require computations unique to that role.

  1. Intrinsic connectivity in the human brain does not reveal networks for ‘basic’ emotions

    PubMed Central

    Lindquist, Kristen A.; Dickerson, Bradford C.; Barrett, Lisa Feldman

    2015-01-01

    We tested two competing models for the brain basis of emotion, the basic emotion theory and the conceptual act theory of emotion, using resting-state functional connectivity magnetic resonance imaging (rs-fcMRI). The basic emotion view hypothesizes that anger, sadness, fear, disgust and happiness each arise from a brain network that is innate, anatomically constrained and homologous in other animals. The conceptual act theory of emotion hypothesizes that an instance of emotion is a brain state constructed from the interaction of domain-general, core systems within the brain such as the salience, default mode and frontoparietal control networks. Using peak coordinates derived from a meta-analysis of task-evoked emotion fMRI studies, we generated a set of whole-brain rs-fcMRI ‘discovery’ maps for each emotion category and examined the spatial overlap in their conjunctions. Instead of discovering a specific network for each emotion category, variance in the discovery maps was accounted for by the known domain-general network. Furthermore, the salience network is observed as part of every emotion category. These results indicate that specific networks for each emotion do not exist within the intrinsic architecture of the human brain and instead support the conceptual act theory of emotion. PMID:25680990

  2. Correspondence of the brain's functional architecture during activation and rest

    PubMed Central

    Smith, Stephen M.; Fox, Peter T.; Miller, Karla L.; Glahn, David C.; Fox, P. Mickle; Mackay, Clare E.; Filippini, Nicola; Watkins, Kate E.; Toro, Roberto; Laird, Angela R.; Beckmann, Christian F.

    2009-01-01

    Neural connections, providing the substrate for functional networks, exist whether or not they are functionally active at any given moment. However, it is not known to what extent brain regions are continuously interacting when the brain is “at rest.” In this work, we identify the major explicit activation networks by carrying out an image-based activation network analysis of thousands of separate activation maps derived from the BrainMap database of functional imaging studies, involving nearly 30,000 human subjects. Independently, we extract the major covarying networks in the resting brain, as imaged with functional magnetic resonance imaging in 36 subjects at rest. The sets of major brain networks, and their decompositions into subnetworks, show close correspondence between the independent analyses of resting and activation brain dynamics. We conclude that the full repertoire of functional networks utilized by the brain in action is continuously and dynamically “active” even when at “rest.” PMID:19620724

  3. Classification and evaluation of the pharmacodynamics of psychotropic drugs by single-lead pharmaco-EEG, EEG mapping and tomography (LORETA).

    PubMed

    Saletu, B; Anderer, P; Saletu-Zyhlarz, G M; Arnold, O; Pascual-Marqui, R D

    2002-01-01

    Utilizing computer-assisted quantitative analyses of human scalp-recorded electroencephalogram (EEG) in combination with certain statistical procedures (quantitative pharmaco-EEG) and mapping techniques (pharmaco-EEG mapping), it is possible to classify psychotropic substances and objectively evaluate their bioavailability at the target organ: the human brain. Specifically, one may determine at an early stage of drug development whether a drug is effective on the central nervous system (CNS) compared with placebo, what its clinical efficacy will be like, at which dosage it acts, when it acts and the equipotent dosages of different galenic formulations. Pharmaco-EEG profiles and maps of neuroleptics, antidepressants, tranquilizers, hypnotics, psychostimulants and nootropics/cognition-enhancing drugs will be described in this paper. Methodological problems, as well as the relationships between acute and chronic drug effects, alterations in normal subjects and patients, CNS effects, therapeutic efficacy and pharmacokinetic and pharmacodynamic data will be discussed. In recent times, imaging of drug effects on the regional brain electrical activity of healthy subjects by means of EEG tomography such as low-resolution electromagnetic tomography (LORETA) has been used for identifying brain areas predominantly involved in psychopharmacological action. This will be demonstrated for the representative drugs of the four main psychopharmacological classes, such as 3 mg haloperidol for neuroleptics, 20 mg citalopram for antidepressants, 2 mg lorazepam for tranquilizers and 20 mg methylphenidate for psychostimulants. LORETA demonstrates that these psychopharmacological classes affect brain structures differently.

  4. EEG topography and tomography (LORETA) in the classification and evaluation of the pharmacodynamics of psychotropic drugs.

    PubMed

    Saletu, Bernd; Anderer, Peter; Saletu-Zyhlarz, Gerda M

    2006-04-01

    By multi-lead computer-assisted quantitative analyses of human scalp-recorded electroencephalogram (QEEG) in combination with certain statistical procedures (quantitative pharmaco-EEG) and mapping techniques (pharmaco-EEG mapping or topography), it is possible to classify psychotropic substances and objectively evaluate their bioavailability at the target organ, the human brain. Specifically, one may determine at an early stage of drug development whether a drug is effective on the central nervous system (CNS) compared with placebo, what its clinical efficacy will be like, at which dosage it acts, when it acts and the equipotent dosages of different galenic formulations. Pharmaco-EEG maps of neuroleptics, antidepressants, tranquilizers, hypnotics, psychostimulants and nootropics/cognition-enhancing drugs will be described. Methodological problems, as well as the relationships between acute and chronic drug effects, alterations in normal subjects and patients, CNS effects and therapeutic efficacy will be discussed. Imaging of drug effects on the regional brain electrical activity of healthy subjects by means of EEG tomography such as low-resolution electromagnetic tomography (LORETA) has been used for identifying brain areas predominantly involved in psychopharmacological action. This will be shown for the representative drugs of the four main psychopharmacological classes, such as 3 mg haloperidol for neuroleptics, 20 mg citalopram for antidepressants, 2 mg lorazepam for tranquilizers and 20 mg methylphenidate for psychostimulants. LORETA demonstrates that these psychopharmacological classes affect brain structures differently. By considering these differences between psychotropic drugs and placebo in normal subjects, as well as between mental disorder patients and normal controls, it may be possible to choose the optimum drug for a specific patient according to a key-lock principle, since the drug should normalize the deviant brain function. Thus, pharmaco-EEG topography and tomography are valuable methods in human neuropsychopharmacology, clinical psychiatry and neurology.

  5. Lifespan Trajectories of White Matter Changes in Rhesus Monkeys.

    PubMed

    Kubicki, M; Baxi, M; Pasternak, O; Tang, Y; Karmacharya, S; Chunga, N; Lyall, A E; Rathi, Y; Eckbo, R; Bouix, S; Mortazavi, F; Papadimitriou, G; Shenton, M E; Westin, C F; Killiany, R; Makris, N; Rosene, D L

    2018-04-26

    Progress in neurodevelopmental brain research has been achieved through the use of animal models. Such models not only help understanding biological changes that govern brain development, maturation and aging, but are also essential for identifying possible mechanisms of neurodevelopmental and age-related chronic disorders, and to evaluate possible interventions with potential relevance to human disease. Genetic relationship of rhesus monkeys to humans makes those animals a great candidate for such models. With the typical lifespan of 25 years, they undergo cognitive maturation and aging that is similar to this observed in humans. Quantitative structural neuroimaging has been proposed as one of the candidate in vivo biomarkers for tracking white matter brain maturation and aging. While lifespan trajectories of white matter changes have been mapped in humans, such knowledge is not available for nonhuman primates. Here, we analyze and model lifespan trajectories of white matter microstructure using in vivo diffusion imaging in a sample of 44 rhesus monkeys. We report quantitative parameters (including slopes and peaks) of lifespan trajectories for 8 individual white matter tracts. We show different trajectories for cellular and extracellular microstructural imaging components that are associated with white matter maturation and aging, and discuss similarities and differences between those in humans and rhesus monkeys, the importance of our findings, and future directions for the field.Significance Statement: Quantitative structural neuroimaging has been proposed as one of the candidate in vivo biomarkers for tracking brain maturation and aging. While lifespan trajectories of structural white matter changes have been mapped in humans, such knowledge is not available for rhesus monkeys. We present here results of the analysis and modeling of the lifespan trajectories of white matter microstructure using in vivo diffusion imaging in a sample of 44 rhesus monkeys (age 4-27). We report and anatomically map lifespan changes related to cellular and extracellular microstructural components that are associated with white matter maturation and aging.

  6. Enhanced cortical thickness measurements for rodent brains via Lagrangian-based RK4 streamline computation

    NASA Astrophysics Data System (ADS)

    Lee, Joohwi; Kim, Sun Hyung; Oguz, Ipek; Styner, Martin

    2016-03-01

    The cortical thickness of the mammalian brain is an important morphological characteristic that can be used to investigate and observe the brain's developmental changes that might be caused by biologically toxic substances such as ethanol or cocaine. Although various cortical thickness analysis methods have been proposed that are applicable for human brain and have developed into well-validated open-source software packages, cortical thickness analysis methods for rodent brains have not yet become as robust and accurate as those designed for human brains. Based on a previously proposed cortical thickness measurement pipeline for rodent brain analysis,1 we present an enhanced cortical thickness pipeline in terms of accuracy and anatomical consistency. First, we propose a Lagrangian-based computational approach in the thickness measurement step in order to minimize local truncation error using the fourth-order Runge-Kutta method. Second, by constructing a line object for each streamline of the thickness measurement, we can visualize the way the thickness is measured and achieve sub-voxel accuracy by performing geometric post-processing. Last, with emphasis on the importance of an anatomically consistent partial differential equation (PDE) boundary map, we propose an automatic PDE boundary map generation algorithm that is specific to rodent brain anatomy, which does not require manual labeling. The results show that the proposed cortical thickness pipeline can produce statistically significant regions that are not observed in the previous cortical thickness analysis pipeline.

  7. Temporal, Diagnostic, and Tissue-Specific Regulation of NRG3 Isoform Expression in Human Brain Development and Affective Disorders.

    PubMed

    Paterson, Clare; Wang, Yanhong; Hyde, Thomas M; Weinberger, Daniel R; Kleinman, Joel E; Law, Amanda J

    2017-03-01

    Genes implicated in schizophrenia are enriched in networks differentially regulated during human CNS development. Neuregulin 3 (NRG3), a brain-enriched neurotrophin, undergoes alternative splicing and is implicated in several neurological disorders with developmental origins. Isoform-specific increases in NRG3 are observed in schizophrenia and associated with rs10748842, a NRG3 risk polymorphism, suggesting NRG3 transcriptional dysregulation as a molecular mechanism of risk. The authors quantitatively mapped the temporal trajectories of NRG3 isoforms (classes I-IV) in the neocortex throughout the human lifespan, examined whether tissue-specific regulation of NRG3 occurs in humans, and determined if abnormalities in NRG3 transcriptomics occur in mood disorders and are genetically determined. NRG3 isoform classes I-IV were quantified using quantitative real-time polymerase chain reaction in human postmortem dorsolateral prefrontal cortex from 286 nonpsychiatric control individuals, from gestational week 14 to 85 years old, and individuals diagnosed with either bipolar disorder (N=34) or major depressive disorder (N=69). Tissue-specific mapping was investigated in several human tissues. rs10748842 was genotyped in individuals with mood disorders, and association with NRG3 isoform expression examined. NRG3 classes displayed individually specific expression trajectories across human neocortical development and aging; classes I, II, and IV were significantly associated with developmental stage. NRG3 class I was increased in bipolar and major depressive disorder, consistent with observations in schizophrenia. NRG3 class II was increased in bipolar disorder, and class III was increased in major depression. The rs10748842 risk genotype predicted elevated class II and III expression, consistent with previous reports in the brain, with tissue-specific analyses suggesting that classes II and III are brain-specific isoforms of NRG3. Mapping the temporal expression of genes during human brain development provides vital insight into gene function and identifies critical sensitive periods whereby genetic factors may influence risk for psychiatric disease. Here the authors provide comprehensive insight into the transcriptional landscape of the psychiatric risk gene, NRG3, in human neocortical development and expand on previous findings in schizophrenia to identify increased expression of developmentally and genetically regulated isoforms in the brain of patients with mood disorders. Principally, the finding that NRG3 classes II and III are brain-specific isoforms predicted by rs10748842 risk genotype and are increased in mood disorders further implicates a molecular mechanism of psychiatric risk at the NRG3 locus and identifies a potential developmental role for NRG3 in bipolar disorder and major depression. These observations encourage investigation of the neurobiology of NRG3 isoforms and highlight inhibition of NRG3 signaling as a potential target for psychiatric treatment development.

  8. Temporal, Diagnostic, and Tissue-Specific Regulation of NRG3 Isoform Expression in Human Brain Development and Affective Disorders

    PubMed Central

    Paterson, Clare; Wang, Yanhong; Hyde, Thomas M.; Weinberger, Daniel R.; Kleinman, Joel E.; Law, Amanda J.

    2018-01-01

    Objective Genes implicated in schizophrenia are enriched in networks differentially regulated during human CNS development. Neuregulin 3 (NRG3), a brain-enriched neurotrophin, undergoes alternative splicing and is implicated in several neurological disorders with developmental origins. Isoform-specific increases in NRG3 are observed in schizophrenia and associated with rs10748842, a NRG3 risk polymorphism, suggesting NRG3 transcriptional dysregulation as a molecular mechanism of risk. The authors quantitatively mapped the temporal trajectories of NRG3 isoforms (classes I–IV) in the neocortex throughout the human lifespan, examined whether tissue-specific regulation of NRG3 occurs in humans, and determined if abnormalities in NRG3 transcriptomics occur in mood disorders and are genetically determined. Method NRG3 isoform classes I–IV were quantified using quantitative real-time polymerase chain reaction in human postmortem dorsolateral prefrontal cortex from 286 nonpsychiatric control individuals, from gestational week 14 to 85 years old, and individuals diagnosed with either bipolar disorder (N=34) or major depressive disorder (N=69). Tissue-specific mapping was investigated in several human tissues. rs10748842 was genotyped in individuals with mood disorders, and association with NRG3 isoform expression examined. Results NRG3 classes displayed individually specific expression trajectories across human neocortical development and aging; classes I, II, and IV were significantly associated with developmental stage. NRG3 class I was increased in bipolar and major depressive disorder, consistent with observations in schizophrenia. NRG3 class II was increased in bipolar disorder, and class III was increased in major depression. The rs10748842 risk genotype predicted elevated class II and III expression, consistent with previous reports in the brain, with tissue-specific analyses suggesting that classes II and III are brain-specific isoforms of NRG3. Conclusions Mapping the temporal expression of genes during human brain development provides vital insight into gene function and identifies critical sensitive periods whereby genetic factors may influence risk for psychiatric disease. Here the authors provide comprehensive insight into the transcriptional landscape of the psychiatric risk gene, NRG3, in human neocortical development and expand on previous findings in schizophrenia to identify increased expression of developmentally and genetically regulated isoforms in the brain of patients with mood disorders. Principally, the finding that NRG3 classes II and III are brain-specific isoforms predicted by rs10748842 risk genotype and are increased in mood disorders further implicates a molecular mechanism of psychiatric risk at the NRG3 locus and identifies a potential developmental role for NRG3 in bipolar disorder and major depression. These observations encourage investigation of the neurobiology of NRG3 isoforms and highlight inhibition of NRG3 signaling as a potential target for psychiatric treatment development. PMID:27771971

  9. Four-dimensional maps of the human somatosensory system

    PubMed Central

    Avanzini, Pietro; Abdollahi, Rouhollah O.; Sartori, Ivana; Caruana, Fausto; Pelliccia, Veronica; Casaceli, Giuseppe; Mai, Roberto; Lo Russo, Giorgio; Rizzolatti, Giacomo; Orban, Guy A.

    2016-01-01

    A fine-grained description of the spatiotemporal dynamics of human brain activity is a major goal of neuroscientific research. Limitations in spatial and temporal resolution of available noninvasive recording and imaging techniques have hindered so far the acquisition of precise, comprehensive four-dimensional maps of human neural activity. The present study combines anatomical and functional data from intracerebral recordings of nearly 100 patients, to generate highly resolved four-dimensional maps of human cortical processing of nonpainful somatosensory stimuli. These maps indicate that the human somatosensory system devoted to the hand encompasses a widespread network covering more than 10% of the cortical surface of both hemispheres. This network includes phasic components, centered on primary somatosensory cortex and neighboring motor, premotor, and inferior parietal regions, and tonic components, centered on opercular and insular areas, and involving human parietal rostroventral area and ventral medial-superior-temporal area. The technique described opens new avenues for investigating the neural basis of all levels of cortical processing in humans. PMID:26976579

  10. Four-dimensional maps of the human somatosensory system.

    PubMed

    Avanzini, Pietro; Abdollahi, Rouhollah O; Sartori, Ivana; Caruana, Fausto; Pelliccia, Veronica; Casaceli, Giuseppe; Mai, Roberto; Lo Russo, Giorgio; Rizzolatti, Giacomo; Orban, Guy A

    2016-03-29

    A fine-grained description of the spatiotemporal dynamics of human brain activity is a major goal of neuroscientific research. Limitations in spatial and temporal resolution of available noninvasive recording and imaging techniques have hindered so far the acquisition of precise, comprehensive four-dimensional maps of human neural activity. The present study combines anatomical and functional data from intracerebral recordings of nearly 100 patients, to generate highly resolved four-dimensional maps of human cortical processing of nonpainful somatosensory stimuli. These maps indicate that the human somatosensory system devoted to the hand encompasses a widespread network covering more than 10% of the cortical surface of both hemispheres. This network includes phasic components, centered on primary somatosensory cortex and neighboring motor, premotor, and inferior parietal regions, and tonic components, centered on opercular and insular areas, and involving human parietal rostroventral area and ventral medial-superior-temporal area. The technique described opens new avenues for investigating the neural basis of all levels of cortical processing in humans.

  11. 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

  12. Comparison of NREM sleep and intravenous sedation through local information processing and whole brain network to explore the mechanism of general anesthesia

    PubMed Central

    Pan, Chuxiong; Xue, Fushan; Xian, Junfang; Huang, Yaqi; Wang, Xiaoyi; He, Huiguang

    2018-01-01

    Background The mechanism of general anesthesia (GA) has been explored for hundreds of years, but unclear. Previous studies indicated a possible correlation between NREM sleep and GA. The purpose of this study is to compare them by in vivo human brain function to probe the neuromechanism of consciousness, so as to find out a clue to GA mechanism. Methods 24 healthy participants were equally assigned to sleep or propofol sedation group by sleeping ability. EEG and Ramsay Sedation Scale were applied to determine sleep stage and sedation depth respectively. Resting-state functional magnetic resonance imaging (RS-fMRI) was acquired at each status. Regional homogeneity (ReHo) and seed-based whole brain functional connectivity maps (WB-FC maps) were compared. Results During sleep, ReHo primarily weakened on frontal lobe (especially preoptic area), but strengthened on brainstem. While during sedation, ReHo changed in various brain areas, including cingulate, precuneus, thalamus and cerebellum. Cingulate, fusiform and insula were concomitance of sleep and sedation. Comparing to sleep, FCs between the cortex and subcortical centers (centralized in cerebellum) were significantly attenuated under sedation. As sedation deepening, cerebellum-based FC maps were diminished, while thalamus- and brainstem-based FC maps were increased. Conclusion There’re huge distinctions in human brain function between sleep and GA. Sleep mainly rely on brainstem and frontal lobe function, while sedation is prone to affect widespread functional network. The most significant differences exist in the precuneus and cingulate, which may play important roles in mechanisms of inducing unconciousness by anesthetics. Trial registration Institutional Review Board (IRB) ChiCTR-IOC-15007454. PMID:29486001

  13. 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

  14. 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.

  15. Regional anatomy of the pedunculopontine nucleus: relevance for deep brain stimulation.

    PubMed

    Fournier-Gosselin, Marie-Pierre; Lipsman, Nir; Saint-Cyr, Jean A; Hamani, Clement; Lozano, Andres M

    2013-09-01

    The pedunculopontine nucleus (PPN) is currently being investigated as a potential deep brain stimulation target to improve gait and posture in Parkinson's disease. This review examines the complex anatomy of the PPN region and suggests a functional mapping of the surrounding nuclei and fiber tracts that may serve as a guide to a more accurate placement of electrodes while avoiding potentially adverse effects. The relationships of the PPN were examined in different human brain atlases. Schematic representations of those structures in the vicinity of the PPN were generated and correlated with their potential stimulation effects. By providing a functional map and representative schematics of the PPN region, we hope to optimize the placement of deep brain stimulation electrodes, thereby maximizing safety and clinical efficacy. © 2013 International Parkinson and Movement Disorder Society.

  16. 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.

  17. 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.

  18. HDAC6 Brain Mapping with [ 18 F]Bavarostat Enabled by a Ru-Mediated Deoxyfluorination

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

    Strebl, Martin G.; Campbell, Arthur J.; Zhao, Wen -Ning

    Histone deacetylase 6 (HDAC6) function and dysregulation have been implicated in the etiology of certain cancers and more recently in central nervous system (CNS) disorders including Rett syndrome, Alzheimer’s and Parkinson’s diseases, and major depressive disorder. HDAC6-selective inhibitors have therapeutic potential, but in the CNS drug space the development of highly brain penetrant HDAC inhibitors has been a persistent challenge. Moreover, no tool exists to directly characterize HDAC6 and its related biology in the living human brain. Here, we report a highly brain penetrant HDAC6 inhibitor, Bavarostat, that exhibits excellent HDAC6 selectivity (>80-fold over all other Zn-containing HDAC paralogues), modulatesmore » tubulin acetylation selectively over histone acetylation, and has excellent brain penetrance. We further demonstrate that Bavarostat can be radiolabeled with 18F by deoxyfluorination through in situ formation of a ruthenium π-complex of the corresponding phenol precursor: the only method currently suitable for synthesis of [ 18F]Bavarostat. In conclusion, by using [ 18F]Bavarostat in a series of rodent and nonhuman primate imaging experiments, we demonstrate its utility for mapping HDAC6 in the living brain, which sets the stage for first-in-human neurochemical imaging of this important target.« less

  19. HDAC6 Brain Mapping with [ 18 F]Bavarostat Enabled by a Ru-Mediated Deoxyfluorination

    DOE PAGES

    Strebl, Martin G.; Campbell, Arthur J.; Zhao, Wen -Ning; ...

    2017-09-06

    Histone deacetylase 6 (HDAC6) function and dysregulation have been implicated in the etiology of certain cancers and more recently in central nervous system (CNS) disorders including Rett syndrome, Alzheimer’s and Parkinson’s diseases, and major depressive disorder. HDAC6-selective inhibitors have therapeutic potential, but in the CNS drug space the development of highly brain penetrant HDAC inhibitors has been a persistent challenge. Moreover, no tool exists to directly characterize HDAC6 and its related biology in the living human brain. Here, we report a highly brain penetrant HDAC6 inhibitor, Bavarostat, that exhibits excellent HDAC6 selectivity (>80-fold over all other Zn-containing HDAC paralogues), modulatesmore » tubulin acetylation selectively over histone acetylation, and has excellent brain penetrance. We further demonstrate that Bavarostat can be radiolabeled with 18F by deoxyfluorination through in situ formation of a ruthenium π-complex of the corresponding phenol precursor: the only method currently suitable for synthesis of [ 18F]Bavarostat. In conclusion, by using [ 18F]Bavarostat in a series of rodent and nonhuman primate imaging experiments, we demonstrate its utility for mapping HDAC6 in the living brain, which sets the stage for first-in-human neurochemical imaging of this important target.« less

  20. High-resolution imaging of the large non-human primate brain using microPET: a feasibility study

    NASA Astrophysics Data System (ADS)

    Naidoo-Variawa, S.; Hey-Cunningham, A. J.; Lehnert, W.; Kench, P. L.; Kassiou, M.; Banati, R.; Meikle, S. R.

    2007-11-01

    The neuroanatomy and physiology of the baboon brain closely resembles that of the human brain and is well suited for evaluating promising new radioligands in non-human primates by PET and SPECT prior to their use in humans. These studies are commonly performed on clinical scanners with 5 mm spatial resolution at best, resulting in sub-optimal images for quantitative analysis. This study assessed the feasibility of using a microPET animal scanner to image the brains of large non-human primates, i.e. papio hamadryas (baboon) at high resolution. Factors affecting image accuracy, including scatter, attenuation and spatial resolution, were measured under conditions approximating a baboon brain and using different reconstruction strategies. Scatter fraction measured 32% at the centre of a 10 cm diameter phantom. Scatter correction increased image contrast by up to 21% but reduced the signal-to-noise ratio. Volume resolution was superior and more uniform using maximum a posteriori (MAP) reconstructed images (3.2-3.6 mm3 FWHM from centre to 4 cm offset) compared to both 3D ordered subsets expectation maximization (OSEM) (5.6-8.3 mm3) and 3D reprojection (3DRP) (5.9-9.1 mm3). A pilot 18F-2-fluoro-2-deoxy-d-glucose ([18F]FDG) scan was performed on a healthy female adult baboon. The pilot study demonstrated the ability to adequately resolve cortical and sub-cortical grey matter structures in the baboon brain and improved contrast when images were corrected for attenuation and scatter and reconstructed by MAP. We conclude that high resolution imaging of the baboon brain with microPET is feasible with appropriate choices of reconstruction strategy and corrections for degrading physical effects. Further work to develop suitable correction algorithms for high-resolution large primate imaging is warranted.

  1. Mapping the connectivity underlying multimodal (verbal and non-verbal) semantic processing: a brain electrostimulation study.

    PubMed

    Moritz-Gasser, Sylvie; Herbet, Guillaume; Duffau, Hugues

    2013-08-01

    Accessing the meaning of words, objects, people and facts is a human ability, made possible thanks to semantic processing. Although studies concerning its cortical organization are proficient, the subcortical connectivity underlying this semantic network received less attention. We used intraoperative direct electrostimulation, which mimics a transient virtual lesion during brain surgery for glioma in eight awaken patients, to map the anatomical white matter substrate subserving the semantic system. Patients performed a picture naming task and a non-verbal semantic association test during the electrical mapping. Direct electrostimulation of the inferior fronto-occipital fascicle, a poorly known ventral association pathway which runs throughout the brain, induced in all cases semantic disturbances. These transient disorders were highly reproducible, and concerned verbal as well as non-verbal output. Our results highlight for the first time the essential role of the left inferior fronto-occipital fascicle in multimodal (and not only in verbal) semantic processing. On the basis of these original findings, and in the lights of phylogenetic considerations regarding this fascicle, we suggest its possible implication in the monitoring of the human level of consciousness related to semantic memory, namely noetic consciousness. Copyright © 2013 Elsevier Ltd. All rights reserved.

  2. 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

  3. Mapping human brain networks with cortico-cortical evoked potentials

    PubMed Central

    Keller, Corey J.; Honey, Christopher J.; Mégevand, Pierre; Entz, Laszlo; Ulbert, Istvan; Mehta, Ashesh D.

    2014-01-01

    The cerebral cortex forms a sheet of neurons organized into a network of interconnected modules that is highly expanded in humans and presumably enables our most refined sensory and cognitive abilities. The links of this network form a fundamental aspect of its organization, and a great deal of research is focusing on understanding how information flows within and between different regions. However, an often-overlooked element of this connectivity regards a causal, hierarchical structure of regions, whereby certain nodes of the cortical network may exert greater influence over the others. While this is difficult to ascertain non-invasively, patients undergoing invasive electrode monitoring for epilepsy provide a unique window into this aspect of cortical organization. In this review, we highlight the potential for cortico-cortical evoked potential (CCEP) mapping to directly measure neuronal propagation across large-scale brain networks with spatio-temporal resolution that is superior to traditional neuroimaging methods. We first introduce effective connectivity and discuss the mechanisms underlying CCEP generation. Next, we highlight how CCEP mapping has begun to provide insight into the neural basis of non-invasive imaging signals. Finally, we present a novel approach to perturbing and measuring brain network function during cognitive processing. The direct measurement of CCEPs in response to electrical stimulation represents a potentially powerful clinical and basic science tool for probing the large-scale networks of the human cerebral cortex. PMID:25180306

  4. Connectopic mapping with resting-state fMRI.

    PubMed

    Haak, Koen V; Marquand, Andre F; Beckmann, Christian F

    2018-04-15

    Brain regions are often topographically connected: nearby locations within one brain area connect with nearby locations in another area. Mapping these connection topographies, or 'connectopies' in short, is crucial for understanding how information is processed in the brain. Here, we propose principled, fully data-driven methods for mapping connectopies using functional magnetic resonance imaging (fMRI) data acquired at rest by combining spectral embedding of voxel-wise connectivity 'fingerprints' with a novel approach to spatial statistical inference. We apply the approach in human primary motor and visual cortex, and show that it can trace biologically plausible, overlapping connectopies in individual subjects that follow these regions' somatotopic and retinotopic maps. As a generic mechanism to perform inference over connectopies, the new spatial statistics approach enables rigorous statistical testing of hypotheses regarding the fine-grained spatial profile of functional connectivity and whether that profile is different between subjects or between experimental conditions. The combined framework offers a fundamental alternative to existing approaches to investigating functional connectivity in the brain, from voxel- or seed-pair wise characterizations of functional association, towards a full, multivariate characterization of spatial topography. Copyright © 2017 The Authors. Published by Elsevier Inc. All rights reserved.

  5. Atlas-guided volumetric diffuse optical tomography enhanced by generalized linear model analysis to image risk decision-making responses in young adults.

    PubMed

    Lin, Zi-Jing; Li, Lin; Cazzell, Mary; Liu, Hanli

    2014-08-01

    Diffuse optical tomography (DOT) is a variant of functional near infrared spectroscopy and has the capability of mapping or reconstructing three dimensional (3D) hemodynamic changes due to brain activity. Common methods used in DOT image analysis to define brain activation have limitations because the selection of activation period is relatively subjective. General linear model (GLM)-based analysis can overcome this limitation. In this study, we combine the atlas-guided 3D DOT image reconstruction with GLM-based analysis (i.e., voxel-wise GLM analysis) to investigate the brain activity that is associated with risk decision-making processes. Risk decision-making is an important cognitive process and thus is an essential topic in the field of neuroscience. The Balloon Analog Risk Task (BART) is a valid experimental model and has been commonly used to assess human risk-taking actions and tendencies while facing risks. We have used the BART paradigm with a blocked design to investigate brain activations in the prefrontal and frontal cortical areas during decision-making from 37 human participants (22 males and 15 females). Voxel-wise GLM analysis was performed after a human brain atlas template and a depth compensation algorithm were combined to form atlas-guided DOT images. In this work, we wish to demonstrate the excellence of using voxel-wise GLM analysis with DOT to image and study cognitive functions in response to risk decision-making. Results have shown significant hemodynamic changes in the dorsal lateral prefrontal cortex (DLPFC) during the active-choice mode and a different activation pattern between genders; these findings correlate well with published literature in functional magnetic resonance imaging (fMRI) and fNIRS studies. Copyright © 2014 The Authors. Human Brain Mapping Published by Wiley Periodicals, Inc.

  6. A Single-Cell Roadmap of Lineage Bifurcation in Human ESC Models of Embryonic Brain Development.

    PubMed

    Yao, Zizhen; Mich, John K; Ku, Sherman; Menon, Vilas; Krostag, Anne-Rachel; Martinez, Refugio A; Furchtgott, Leon; Mulholland, Heather; Bort, Susan; Fuqua, Margaret A; Gregor, Ben W; Hodge, Rebecca D; Jayabalu, Anu; May, Ryan C; Melton, Samuel; Nelson, Angelique M; Ngo, N Kiet; Shapovalova, Nadiya V; Shehata, Soraya I; Smith, Michael W; Tait, Leah J; Thompson, Carol L; Thomsen, Elliot R; Ye, Chaoyang; Glass, Ian A; Kaykas, Ajamete; Yao, Shuyuan; Phillips, John W; Grimley, Joshua S; Levi, Boaz P; Wang, Yanling; Ramanathan, Sharad

    2017-01-05

    During human brain development, multiple signaling pathways generate diverse cell types with varied regional identities. Here, we integrate single-cell RNA sequencing and clonal analyses to reveal lineage trees and molecular signals underlying early forebrain and mid/hindbrain cell differentiation from human embryonic stem cells (hESCs). Clustering single-cell transcriptomic data identified 41 distinct populations of progenitor, neuronal, and non-neural cells across our differentiation time course. Comparisons with primary mouse and human gene expression data demonstrated rostral and caudal progenitor and neuronal identities from early brain development. Bayesian analyses inferred a unified cell-type lineage tree that bifurcates between cortical and mid/hindbrain cell types. Two methods of clonal analyses confirmed these findings and further revealed the importance of Wnt/β-catenin signaling in controlling this lineage decision. Together, these findings provide a rich transcriptome-based lineage map for studying human brain development and modeling developmental disorders. Copyright © 2017 Elsevier Inc. All rights reserved.

  7. Evidence from intrinsic activity that asymmetry of the human brain is controlled by multiple factors.

    PubMed

    Liu, Hesheng; Stufflebeam, Steven M; Sepulcre, Jorge; Hedden, Trey; Buckner, Randy L

    2009-12-01

    Cerebral lateralization is a fundamental property of the human brain and a marker of successful development. Here we provide evidence that multiple mechanisms control asymmetry for distinct brain systems. Using intrinsic activity to measure asymmetry in 300 adults, we mapped the most strongly lateralized brain regions. Both men and women showed strong asymmetries with a significant, but small, group difference. Factor analysis on the asymmetric regions revealed 4 separate factors that each accounted for significant variation across subjects. The factors were associated with brain systems involved in vision, internal thought (the default network), attention, and language. An independent sample of right- and left-handed individuals showed that hand dominance affects brain asymmetry but differentially across the 4 factors supporting their independence. These findings show the feasibility of measuring brain asymmetry using intrinsic activity fluctuations and suggest that multiple genetic or environmental mechanisms control cerebral lateralization.

  8. Artifact correction in diffusion MRI of non-human primate brains on a clinical 3T scanner.

    PubMed

    Zhang, Xiaodong; Kirsch, John E; Zhong, Xiaodong

    2016-02-01

    Smearing artifacts were observed and investigated in diffusion tensor imaging (DTI) studies of macaque monkeys on a clinical whole-body 3T scanner. Four adult macaques were utilized to evaluate DTI artifacts. DTI images were acquired with a single-shot echo-planar imaging (EPI) sequence using a parallel imaging technique. The smearing artifacts observed on the diffusion-weighted images and fractional anisotropy maps were caused by the incomplete fat suppression due to the irregular macaque frontal skull geometry and anatomy. The artifact can be reduced substantially using a novel three-dimensional (3D) shimming procedure. The smearing artifacts observed on diffusion weighted images and fractional anisotropy (FA) maps of macaque brains can be reduced substantially using a robust 3D shimming approach. The DTI protocol combined with the shimming procedure could be a robust approach to examine brain connectivity and white matter integrity of non-human primates using a conventional clinical setting. © 2015 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  9. Using UMLS to construct a generalized hierarchical concept-based dictionary of brain functions for information extraction from the fMRI literature.

    PubMed

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

    2009-10-01

    With a rapid progress in the field, a great many fMRI studies are published every year, to the extent that it is now becoming difficult for researchers to keep up with the literature, since reading papers is extremely time-consuming and labor-intensive. Thus, automatic information extraction has become an important issue. In this study, we used the Unified Medical Language System (UMLS) to construct a hierarchical concept-based dictionary of brain functions. To the best of our knowledge, this is the first generalized dictionary of this kind. We also developed an information extraction system for recognizing, mapping and classifying terms relevant to human brain study. The precision and recall of our system was on a par with that of human experts in term recognition, term mapping and term classification. Our approach presented in this paper presents an alternative to the more laborious, manual entry approach to information extraction.

  10. Understand the cogs to understand cognition.

    PubMed

    Marblestone, Adam H; Wayne, Greg; Kording, Konrad P

    2017-01-01

    Lake et al. suggest that current AI systems lack the inductive biases that enable human learning. However, Lake et al.'s proposed biases may not directly map onto mechanisms in the developing brain. A convergence of fields may soon create a correspondence between biological neural circuits and optimization in structured architectures, allowing us to systematically dissect how brains learn.

  11. Rapid and minimum invasive functional brain mapping by real-time visualization of high gamma activity during awake craniotomy.

    PubMed

    Ogawa, Hiroshi; Kamada, Kyousuke; Kapeller, Christoph; Hiroshima, Satoru; Prueckl, Robert; Guger, Christoph

    2014-11-01

    Electrocortical stimulation (ECS) is the gold standard for functional brain mapping during an awake craniotomy. The critical issue is to set aside enough time to identify eloquent cortices by ECS. High gamma activity (HGA) ranging between 80 and 120 Hz on electrocorticogram is assumed to reflect localized cortical processing. In this report, we used real-time HGA mapping and functional neuronavigation integrated with functional magnetic resonance imaging (fMRI) for rapid and reliable identification of motor and language functions. Four patients with intra-axial tumors in their dominant hemisphere underwent preoperative fMRI and lesion resection with an awake craniotomy. All patients showed significant fMRI activation evoked by motor and language tasks. During the craniotomy, we recorded electrocorticogram activity by placing subdural grids directly on the exposed brain surface. Each patient performed motor and language tasks and demonstrated real-time HGA dynamics in hand motor areas and parts of the inferior frontal gyrus. Sensitivity and specificity of HGA mapping were 100% compared with ECS mapping in the frontal lobe, which suggested HGA mapping precisely indicated eloquent cortices. We found different HGA dynamics of language tasks in frontal and temporal regions. Specificities of the motor and language-fMRI did not reach 85%. The results of HGA mapping was mostly consistent with those of ECS mapping, although fMRI tended to overestimate functional areas. This novel technique enables rapid and accurate identification of motor and frontal language areas. Furthermore, real-time HGA mapping sheds light on underlying physiological mechanisms related to human brain functions. Copyright © 2014 Elsevier Inc. All rights reserved.

  12. Social Distance Evaluation in Human Parietal Cortex

    PubMed Central

    Yamakawa, Yoshinori; Kanai, Ryota; Matsumura, Michikazu; Naito, Eiichi

    2009-01-01

    Across cultures, social relationships are often thought of, described, and acted out in terms of physical space (e.g. “close friends” “high lord”). Does this cognitive mapping of social concepts arise from shared brain resources for processing social and physical relationships? Using fMRI, we found that the tasks of evaluating social compatibility and of evaluating physical distances engage a common brain substrate in the parietal cortex. The present study shows the possibility of an analytic brain mechanism to process and represent complex networks of social relationships. Given parietal cortex's known role in constructing egocentric maps of physical space, our present findings may help to explain the linguistic, psychological and behavioural links between social and physical space. PMID:19204791

  13. Mechanism of orientation of stimulating currents in magnetic brain stimulation (abstract)

    NASA Astrophysics Data System (ADS)

    Ueno, S.; Matsuda, T.

    1991-04-01

    We made a functional map of the human motor cortex related to the hand and foot areas by stimulating the human brain with a focused magnetic pulse. We observed that each functional area in the cortex has an optimum direction for which stimulating currents can produce neural excitation. The present report focuses on the mechanism which is responsible for producing this anisotropic response to brain stimulation. We first obtained a functional map of the brain related to the left ADM (abductor digiti minimi muscles). When the stimulating currents were aligned in the direction from the left to the right hemisphere, clear EMG (electromyographic) responses were obtained only from the left ADM to magnetic stimulation of both hemisphere. When the stimulating currents were aligned in the direction from the right to the left hemisphere, clear EMG signals were obtained only from the right ADM to magnetic stimulation of both hemisphere. The functional maps of the brain were sensitive to changes in the direction of the stimulating currents. To explain the phenomena obtained in the experiments, we developed a model of neural excitation elicited by magnetic stimulation. When eddy currents which are induced by pulsed magnetic fields flow in the direction from soma to the distal part of neural fiber, depolarized area in the distal part are excited, and the membrane excitation propagates along the nerve fiber. In contrast, when the induced currents flow in the direction from the distal part to soma, hyperpolarized parts block or inhibit neural excitation even if the depolarized parts near the soma can be excited. The model explains our observation that the orientation of the induced current vectors reflect both the functional and anatomical organization of the neural fibers in the brain.

  14. Haptic contents of a movie dynamically engage the spectator's sensorimotor cortex.

    PubMed

    Lankinen, Kaisu; Smeds, Eero; Tikka, Pia; Pihko, Elina; Hari, Riitta; Koskinen, Miika

    2016-11-01

    Observation of another person's actions and feelings activates brain areas that support similar functions in the observer, thereby facilitating inferences about the other's mental and bodily states. In real life, events eliciting this kind of vicarious brain activations are intermingled with other complex, ever-changing stimuli in the environment. One practical approach to study the neural underpinnings of real-life vicarious perception is to image brain activity during movie viewing. Here the goal was to find out how observed haptic events in a silent movie would affect the spectator's sensorimotor cortex. The functional state of the sensorimotor cortex was monitored by analyzing, in 16 healthy subjects, magnetoencephalographic (MEG) responses to tactile finger stimuli that were presented once per second throughout the session. Using canonical correlation analysis and spatial filtering, consistent single-trial responses across subjects were uncovered, and their waveform changes throughout the movie were quantified. The long-latency (85-175 ms) parts of the responses were modulated in concordance with the participants' average moment-by-moment ratings of own engagement in the haptic content of the movie (correlation r = 0.49; ratings collected after the MEG session). The results, obtained by using novel signal-analysis approaches, demonstrate that the functional state of the human sensorimotor cortex fluctuates in a fine-grained manner even during passive observation of temporally varying haptic events. Hum Brain Mapp 37:4061-4068, 2016. © 2016 The Authors Human Brain Mapping Published by Wiley Periodicals, Inc. © 2016 The Authors Human Brain Mapping Published by Wiley Periodicals, Inc.

  15. 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

  16. Human brain lesion-deficit inference remapped.

    PubMed

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

    2014-09-01

    Our knowledge of the anatomical organization of the human brain in health and disease draws heavily on the study of patients with focal brain lesions. Historically the first method of mapping brain function, it is still potentially the most powerful, establishing the necessity of any putative neural substrate for a given function or deficit. Great inferential power, however, carries a crucial vulnerability: without stronger alternatives any consistent error cannot be easily detected. A hitherto unexamined source of such error is the structure of the high-dimensional distribution of patterns of focal damage, especially in ischaemic injury-the commonest aetiology in lesion-deficit studies-where the anatomy is naturally shaped by the architecture of the vascular tree. This distribution is so complex that analysis of lesion data sets of conventional size cannot illuminate its structure, leaving us in the dark about the presence or absence of such error. To examine this crucial question we assembled the largest known set of focal brain lesions (n = 581), derived from unselected patients with acute ischaemic injury (mean age = 62.3 years, standard deviation = 17.8, male:female ratio = 0.547), visualized with diffusion-weighted magnetic resonance imaging, and processed with validated automated lesion segmentation routines. High-dimensional analysis of this data revealed a hidden bias within the multivariate patterns of damage that will consistently distort lesion-deficit maps, displacing inferred critical regions from their true locations, in a manner opaque to replication. Quantifying the size of this mislocalization demonstrates that past lesion-deficit relationships estimated with conventional inferential methodology are likely to be significantly displaced, by a magnitude dependent on the unknown underlying lesion-deficit relationship itself. Past studies therefore cannot be retrospectively corrected, except by new knowledge that would render them redundant. Positively, we show that novel machine learning techniques employing high-dimensional inference can nonetheless accurately converge on the true locus. We conclude that current inferences about human brain function and deficits based on lesion mapping must be re-evaluated with methodology that adequately captures the high-dimensional structure of lesion data. © The Author (2014). Published by Oxford University Press on behalf of the Guarantors of Brain.

  17. 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.

  18. Model of brain activation predicts the neural collective influence map of the brain

    PubMed Central

    Morone, Flaviano; Roth, Kevin; Min, Byungjoon; Makse, Hernán A.

    2017-01-01

    Efficient complex systems have a modular structure, but modularity does not guarantee robustness, because efficiency also requires an ingenious interplay of the interacting modular components. The human brain is the elemental paradigm of an efficient robust modular system interconnected as a network of networks (NoN). Understanding the emergence of robustness in such modular architectures from the interconnections of its parts is a longstanding challenge that has concerned many scientists. Current models of dependencies in NoN inspired by the power grid express interactions among modules with fragile couplings that amplify even small shocks, thus preventing functionality. Therefore, we introduce a model of NoN to shape the pattern of brain activations to form a modular environment that is robust. The model predicts the map of neural collective influencers (NCIs) in the brain, through the optimization of the influence of the minimal set of essential nodes responsible for broadcasting information to the whole-brain NoN. Our results suggest intervention protocols to control brain activity by targeting influential neural nodes predicted by network theory. PMID:28351973

  19. 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.

  20. Doubly Selective Multiple Quantum Chemical Shift Imaging and T1 Relaxation Time Measurement of Glutathione (GSH) in the Human Brain In Vivo

    PubMed Central

    Choi, In-Young; Lee, Phil

    2012-01-01

    Mapping of a major antioxidant, glutathione (GSH), was achieved in the human brain in vivo using a doubly selective multiple quantum filtering based chemical shift imaging (CSI) of GSH at 3 T. Both in vivo and phantom tests in CSI and single voxel measurements were consistent with excellent suppression of overlapping signals from creatine, γ-Amino butyric acid (GABA) and macromolecules. The GSH concentration in the fronto-parietal region was 1.20 ± 0.16 µmol/g (mean ± SD, n = 7). The longitudinal relaxation time (T1) of GSH in the human brain was 397 ± 44 ms (mean ± SD, n = 5), which was substantially shorter than those of other metabolites. This GSH CSI method permits us to address regional differences of GSH in the human brain with conditions where oxidative stress has been implicated, including multiple sclerosis, aging and neurodegenerative diseases. PMID:22730142

  1. Unmasking Language Lateralization in Human Brain Intrinsic Activity

    PubMed Central

    McAvoy, Mark; Mitra, Anish; Coalson, Rebecca S.; d'Avossa, Giovanni; Keidel, James L.; Petersen, Steven E.; Raichle, Marcus E.

    2016-01-01

    Lateralization of function is a fundamental feature of the human brain as exemplified by the left hemisphere dominance of language. Despite the prominence of lateralization in the lesion, split-brain and task-based fMRI literature, surprisingly little asymmetry has been revealed in the increasingly popular functional imaging studies of spontaneous fluctuations in the fMRI BOLD signal (so-called resting-state fMRI). Here, we show the global signal, an often discarded component of the BOLD signal in resting-state studies, reveals a leftward asymmetry that maps onto regions preferential for semantic processing in left frontal and temporal cortex and the right cerebellum and a rightward asymmetry that maps onto putative attention-related regions in right frontal, temporoparietal, and parietal cortex. Hemispheric asymmetries in the global signal resulted from amplitude modulation of the spontaneous fluctuations. To confirm these findings obtained from normal, healthy, right-handed subjects in the resting-state, we had them perform 2 semantic processing tasks: synonym and numerical magnitude judgment and sentence comprehension. In addition to establishing a new technique for studying lateralization through functional imaging of the resting-state, our findings shed new light on the physiology of the global brain signal. PMID:25636911

  2. DICCCOL: Dense Individualized and Common Connectivity-Based Cortical Landmarks

    PubMed Central

    Zhu, Dajiang; Guo, Lei; Jiang, Xi; Zhang, Tuo; Zhang, Degang; Chen, Hanbo; Deng, Fan; Faraco, Carlos; Jin, Changfeng; Wee, Chong-Yaw; Yuan, Yixuan; Lv, Peili; Yin, Yan; Hu, Xiaolei; Duan, Lian; Hu, Xintao; Han, Junwei; Wang, Lihong; Shen, Dinggang; Miller, L Stephen

    2013-01-01

    Is there a common structural and functional cortical architecture that can be quantitatively encoded and precisely reproduced across individuals and populations? This question is still largely unanswered due to the vast complexity, variability, and nonlinearity of the cerebral cortex. Here, we hypothesize that the common cortical architecture can be effectively represented by group-wise consistent structural fiber connections and take a novel data-driven approach to explore the cortical architecture. We report a dense and consistent map of 358 cortical landmarks, named Dense Individualized and Common Connectivity–based Cortical Landmarks (DICCCOLs). Each DICCCOL is defined by group-wise consistent white-matter fiber connection patterns derived from diffusion tensor imaging (DTI) data. Our results have shown that these 358 landmarks are remarkably reproducible over more than one hundred human brains and possess accurate intrinsically established structural and functional cross-subject correspondences validated by large-scale functional magnetic resonance imaging data. In particular, these 358 cortical landmarks can be accurately and efficiently predicted in a new single brain with DTI data. Thus, this set of 358 DICCCOL landmarks comprehensively encodes the common structural and functional cortical architectures, providing opportunities for many applications in brain science including mapping human brain connectomes, as demonstrated in this work. PMID:22490548

  3. Morphology enabled dipole inversion (MEDI) from a single-angle acquisition: comparison with COSMOS in human brain imaging.

    PubMed

    Liu, Tian; Liu, Jing; de Rochefort, Ludovic; Spincemaille, Pascal; Khalidov, Ildar; Ledoux, James Robert; Wang, Yi

    2011-09-01

    Magnetic susceptibility varies among brain structures and provides insights into the chemical and molecular composition of brain tissues. However, the determination of an arbitrary susceptibility distribution from the measured MR signal phase is a challenging, ill-conditioned inverse problem. Although a previous method named calculation of susceptibility through multiple orientation sampling (COSMOS) has solved this inverse problem both theoretically and experimentally using multiple angle acquisitions, it is often impractical to carry out on human subjects. Recently, the feasibility of calculating the brain susceptibility distribution from a single-angle acquisition was demonstrated using morphology enabled dipole inversion (MEDI). In this study, we further improved the original MEDI method by sparsifying the edges in the quantitative susceptibility map that do not have a corresponding edge in the magnitude image. Quantitative susceptibility maps generated by the improved MEDI were compared qualitatively and quantitatively with those generated by calculation of susceptibility through multiple orientation sampling. The results show a high degree of agreement between MEDI and calculation of susceptibility through multiple orientation sampling, and the practicality of MEDI allows many potential clinical applications. Copyright © 2011 Wiley-Liss, Inc.

  4. Human brain atlas for automated region of interest selection in quantitative susceptibility mapping: application to determine iron content in deep gray matter structures.

    PubMed

    Lim, Issel Anne L; Faria, Andreia V; Li, Xu; Hsu, Johnny T C; Airan, Raag D; Mori, Susumu; van Zijl, Peter C M

    2013-11-15

    The purpose of this paper is to extend the single-subject Eve atlas from Johns Hopkins University, which currently contains diffusion tensor and T1-weighted anatomical maps, by including contrast based on quantitative susceptibility mapping. The new atlas combines a "deep gray matter parcellation map" (DGMPM) derived from a single-subject quantitative susceptibility map with the previously established "white matter parcellation map" (WMPM) from the same subject's T1-weighted and diffusion tensor imaging data into an MNI coordinate map named the "Everything Parcellation Map in Eve Space," also known as the "EvePM." It allows automated segmentation of gray matter and white matter structures. Quantitative susceptibility maps from five healthy male volunteers (30 to 33 years of age) were coregistered to the Eve Atlas with AIR and Large Deformation Diffeomorphic Metric Mapping (LDDMM), and the transformation matrices were applied to the EvePM to produce automated parcellation in subject space. Parcellation accuracy was measured with a kappa analysis for the left and right structures of six deep gray matter regions. For multi-orientation QSM images, the Kappa statistic was 0.85 between automated and manual segmentation, with the inter-rater reproducibility Kappa being 0.89 for the human raters, suggesting "almost perfect" agreement between all segmentation methods. Segmentation seemed slightly more difficult for human raters on single-orientation QSM images, with the Kappa statistic being 0.88 between automated and manual segmentation, and 0.85 and 0.86 between human raters. Overall, this atlas provides a time-efficient tool for automated coregistration and segmentation of quantitative susceptibility data to analyze many regions of interest. These data were used to establish a baseline for normal magnetic susceptibility measurements for over 60 brain structures of 30- to 33-year-old males. Correlating the average susceptibility with age-based iron concentrations in gray matter structures measured by Hallgren and Sourander (1958) allowed interpolation of the average iron concentration of several deep gray matter regions delineated in the EvePM. Copyright © 2013 Elsevier Inc. All rights reserved.

  5. Mapping Cortical Laminar Structure in the 3D BigBrain.

    PubMed

    Wagstyl, Konrad; Lepage, Claude; Bludau, Sebastian; Zilles, Karl; Fletcher, Paul C; Amunts, Katrin; Evans, Alan C

    2018-07-01

    Histological sections offer high spatial resolution to examine laminar architecture of the human cerebral cortex; however, they are restricted by being 2D, hence only regions with sufficiently optimal cutting planes can be analyzed. Conversely, noninvasive neuroimaging approaches are whole brain but have relatively low resolution. Consequently, correct 3D cross-cortical patterns of laminar architecture have never been mapped in histological sections. We developed an automated technique to identify and analyze laminar structure within the high-resolution 3D histological BigBrain. We extracted white matter and pial surfaces, from which we derived histologically verified surfaces at the layer I/II boundary and within layer IV. Layer IV depth was strongly predicted by cortical curvature but varied between areas. This fully automated 3D laminar analysis is an important requirement for bridging high-resolution 2D cytoarchitecture and in vivo 3D neuroimaging. It lays the foundation for in-depth, whole-brain analyses of cortical layering.

  6. Entrepreneurial and parental love-are they the same?

    PubMed

    Halko, Marja-Liisa; Lahti, Tom; Hytönen, Kaisa; Jääskeläinen, Iiro P

    2017-06-01

    Here we tested the hypothesis that entrepreneurs' emotional experience and brain responses toward their own firm resemble those of parents toward their own children. Using fMRI, we measured the brain activity while male entrepreneurs viewed pictures of their own and of a familiar firm, and while fathers viewed pictures of their own and of a familiar child. The entrepreneurs who self-rated as being very closely attached with their venture showed a similar suppression of activity in the posterior cingulate cortex, temporoparietal junction, and dorsomedial prefrontal cortex as fathers during viewing pictures of their own children versus familiar children. In addition, individual differences in the confidence trait influenced the neural encoding of both paternal and entrepreneurial processing. For underconfident fathers, a picture of one's own child was associated with stronger activation and for overconfident fathers with weaker activation in the amygdala and in caudate nucleus, a brain structure associated with processing of rewards. Similar association with activation, yet more widespread in the emotional processing network, was observed in entrepreneurs suggesting a similar neural basis for increased sensitivity to threats and potential risks concerning one's venture and child. In conclusion, both entrepreneurial and parental love seem to be supported by brain structures associated with reward and emotional processing as well as social understanding. Hum Brain Mapp 38:2923-2938, 2017. © 2017 The Authors Human Brain Mapping Published by Wiley Periodicals, Inc. © 2017 The Authors Human Brain Mapping Published by Wiley Periodicals, Inc.

  7. Mapping human brain networks with cortico-cortical evoked potentials.

    PubMed

    Keller, Corey J; Honey, Christopher J; Mégevand, Pierre; Entz, Laszlo; Ulbert, Istvan; Mehta, Ashesh D

    2014-10-05

    The cerebral cortex forms a sheet of neurons organized into a network of interconnected modules that is highly expanded in humans and presumably enables our most refined sensory and cognitive abilities. The links of this network form a fundamental aspect of its organization, and a great deal of research is focusing on understanding how information flows within and between different regions. However, an often-overlooked element of this connectivity regards a causal, hierarchical structure of regions, whereby certain nodes of the cortical network may exert greater influence over the others. While this is difficult to ascertain non-invasively, patients undergoing invasive electrode monitoring for epilepsy provide a unique window into this aspect of cortical organization. In this review, we highlight the potential for cortico-cortical evoked potential (CCEP) mapping to directly measure neuronal propagation across large-scale brain networks with spatio-temporal resolution that is superior to traditional neuroimaging methods. We first introduce effective connectivity and discuss the mechanisms underlying CCEP generation. Next, we highlight how CCEP mapping has begun to provide insight into the neural basis of non-invasive imaging signals. Finally, we present a novel approach to perturbing and measuring brain network function during cognitive processing. The direct measurement of CCEPs in response to electrical stimulation represents a potentially powerful clinical and basic science tool for probing the large-scale networks of the human cerebral cortex. © 2014 The Author(s) Published by the Royal Society. All rights reserved.

  8. 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.

  9. Mapping Multiplex Hubs in Human Functional Brain Networks

    PubMed Central

    De Domenico, Manlio; Sasai, Shuntaro; Arenas, Alex

    2016-01-01

    Typical brain networks consist of many peripheral regions and a few highly central ones, i.e., hubs, playing key functional roles in cerebral inter-regional interactions. Studies have shown that networks, obtained from the analysis of specific frequency components of brain activity, present peculiar architectures with unique profiles of region centrality. However, the identification of hubs in networks built from different frequency bands simultaneously is still a challenging problem, remaining largely unexplored. Here we identify each frequency component with one layer of a multiplex network and face this challenge by exploiting the recent advances in the analysis of multiplex topologies. First, we show that each frequency band carries unique topological information, fundamental to accurately model brain functional networks. We then demonstrate that hubs in the multiplex network, in general different from those ones obtained after discarding or aggregating the measured signals as usual, provide a more accurate map of brain's most important functional regions, allowing to distinguish between healthy and schizophrenic populations better than conventional network approaches. PMID:27471443

  10. The dynamics of error processing in the human brain as reflected by high-gamma activity in noninvasive and intracranial EEG.

    PubMed

    Völker, Martin; Fiederer, Lukas D J; Berberich, Sofie; Hammer, Jiří; Behncke, Joos; Kršek, Pavel; Tomášek, Martin; Marusič, Petr; Reinacher, Peter C; Coenen, Volker A; Helias, Moritz; Schulze-Bonhage, Andreas; Burgard, Wolfram; Ball, Tonio

    2018-06-01

    Error detection in motor behavior is a fundamental cognitive function heavily relying on local cortical information processing. Neural activity in the high-gamma frequency band (HGB) closely reflects such local cortical processing, but little is known about its role in error processing, particularly in the healthy human brain. Here we characterize the error-related response of the human brain based on data obtained with noninvasive EEG optimized for HGB mapping in 31 healthy subjects (15 females, 16 males), and additional intracranial EEG data from 9 epilepsy patients (4 females, 5 males). Our findings reveal a multiscale picture of the global and local dynamics of error-related HGB activity in the human brain. On the global level as reflected in the noninvasive EEG, the error-related response started with an early component dominated by anterior brain regions, followed by a shift to parietal regions, and a subsequent phase characterized by sustained parietal HGB activity. This phase lasted for more than 1 s after the error onset. On the local level reflected in the intracranial EEG, a cascade of both transient and sustained error-related responses involved an even more extended network, spanning beyond frontal and parietal regions to the insula and the hippocampus. HGB mapping appeared especially well suited to investigate late, sustained components of the error response, possibly linked to downstream functional stages such as error-related learning and behavioral adaptation. Our findings establish the basic spatio-temporal properties of HGB activity as a neural correlate of error processing, complementing traditional error-related potential studies. Copyright © 2018 The Authors. Published by Elsevier Inc. All rights reserved.

  11. 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

  12. Outer brain barriers in rat and human development

    PubMed Central

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

    2015-01-01

    Complex barriers at the brain's surface, particularly in development, are poorly defined. In the adult, arachnoid blood-cerebrospinal fluid (CSF) barrier separates the fenestrated dural vessels from the CSF by means of a cell layer joined by tight junctions. Outer CSF-brain barrier provides diffusion restriction between brain and subarachnoid CSF through an initial radial glial end feet layer covered with a pial surface layer. To further characterize these interfaces we examined embryonic rat brains from E10 to P0 and forebrains from human embryos and fetuses (6–21st weeks post-conception) and adults using immunohistochemistry and confocal microscopy. Antibodies against claudin-11, BLBP, collagen 1, SSEA-4, MAP2, YKL-40, and its receptor IL-13Rα2 and EAAT1 were used to describe morphological characteristics and functional aspects of the outer brain barriers. Claudin-11 was a reliable marker of the arachnoid blood-CSF barrier. Collagen 1 delineated the subarachnoid space and stained pial surface layer. BLBP defined radial glial end feet layer and SSEA-4 and YKL-40 were present in both leptomeningeal cells and end feet layer, which transformed into glial limitans. IL-13Rα2 and EAAT1 were present in the end feet layer illustrating transporter/receptor presence in the outer CSF-brain barrier. MAP2 immunostaining in adult brain outlined the lower border of glia limitans; remnants of end feet were YKL-40 positive in some areas. We propose that outer brain barriers are composed of at least 3 interfaces: blood-CSF barrier across arachnoid barrier cell layer, blood-CSF barrier across pial microvessels, and outer CSF-brain barrier comprising glial end feet layer/pial surface layer. PMID:25852456

  13. Outer brain barriers in rat and human development.

    PubMed

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

    2015-01-01

    Complex barriers at the brain's surface, particularly in development, are poorly defined. In the adult, arachnoid blood-cerebrospinal fluid (CSF) barrier separates the fenestrated dural vessels from the CSF by means of a cell layer joined by tight junctions. Outer CSF-brain barrier provides diffusion restriction between brain and subarachnoid CSF through an initial radial glial end feet layer covered with a pial surface layer. To further characterize these interfaces we examined embryonic rat brains from E10 to P0 and forebrains from human embryos and fetuses (6-21st weeks post-conception) and adults using immunohistochemistry and confocal microscopy. Antibodies against claudin-11, BLBP, collagen 1, SSEA-4, MAP2, YKL-40, and its receptor IL-13Rα2 and EAAT1 were used to describe morphological characteristics and functional aspects of the outer brain barriers. Claudin-11 was a reliable marker of the arachnoid blood-CSF barrier. Collagen 1 delineated the subarachnoid space and stained pial surface layer. BLBP defined radial glial end feet layer and SSEA-4 and YKL-40 were present in both leptomeningeal cells and end feet layer, which transformed into glial limitans. IL-13Rα2 and EAAT1 were present in the end feet layer illustrating transporter/receptor presence in the outer CSF-brain barrier. MAP2 immunostaining in adult brain outlined the lower border of glia limitans; remnants of end feet were YKL-40 positive in some areas. We propose that outer brain barriers are composed of at least 3 interfaces: blood-CSF barrier across arachnoid barrier cell layer, blood-CSF barrier across pial microvessels, and outer CSF-brain barrier comprising glial end feet layer/pial surface layer.

  14. Rapid simultaneous high-resolution mapping of myelin water fraction and relaxation times in human brain using BMC-mcDESPOT.

    PubMed

    Bouhrara, Mustapha; Spencer, Richard G

    2017-02-15

    A number of central nervous system (CNS) diseases exhibit changes in myelin content and magnetic resonance longitudinal, T 1 , and transverse, T 2 , relaxation times, which therefore represent important biomarkers of CNS pathology. Among the methods applied for measurement of myelin water fraction (MWF) and relaxation times, the multicomponent driven equilibrium single pulse observation of T 1 and T 2 (mcDESPOT) approach is of particular interest. mcDESPOT permits whole brain mapping of multicomponent T 1 and T 2 , with data acquisition accomplished within a clinically realistic acquisition time. Unfortunately, previous studies have indicated the limited performance of mcDESPOT in the setting of the modest signal-to-noise range of high-resolution mapping, required for the depiction of small structures and to reduce partial volume effects. Recently, we showed that a new Bayesian Monte Carlo (BMC) analysis substantially improved determination of MWF from mcDESPOT imaging data. However, our previous study was limited in that it did not discuss determination of relaxation times. Here, we extend the BMC analysis to the simultaneous determination of whole-brain MWF and relaxation times using the two-component mcDESPOT signal model. Simulation analyses and in-vivo human brain studies indicate the overall greater performance of this approach compared to the stochastic region contraction (SRC) algorithm, conventionally used to derive parameter estimates from mcDESPOT data. SRC estimates of the transverse relaxation time of the long T 2 fraction, T 2,l , and the longitudinal relaxation time of the short T 1 fraction, T 1,s , clustered towards the lower and upper parameter search space limits, respectively, indicating failure of the fitting procedure. We demonstrate that this effect is absent in the BMC analysis. Our results also showed improved parameter estimation for BMC as compared to SRC for high-resolution mapping. Overall we find that the combination of BMC analysis and mcDESPOT, BMC-mcDESPOT, shows excellent performance for accurate high-resolution whole-brain mapping of MWF and bi-component transverse and longitudinal relaxation times within a clinically realistic acquisition time. Published by Elsevier Inc.

  15. Optimization of Brain T2 Mapping Using Standard CPMG Sequence In A Clinical Scanner

    NASA Astrophysics Data System (ADS)

    Hnilicová, P.; Bittšanský, M.; Dobrota, D.

    2014-04-01

    In magnetic resonance imaging, transverse relaxation time (T2) mapping is a useful quantitative tool enabling enhanced diagnostics of many brain pathologies. The aim of our study was to test the influence of different sequence parameters on calculated T2 values, including multi-slice measurements, slice position, interslice gap, echo spacing, and pulse duration. Measurements were performed using standard multi-slice multi-echo CPMG imaging sequence on a 1.5 Tesla routine whole body MR scanner. We used multiple phantoms with different agarose concentrations (0 % to 4 %) and verified the results on a healthy volunteer. It appeared that neither the pulse duration, the size of interslice gap nor the slice shift had any impact on the T2. The measurement accuracy was increased with shorter echo spacing. Standard multi-slice multi-echo CPMG protocol with the shortest echo spacing, also the smallest available interslice gap (100 % of slice thickness) and shorter pulse duration was found to be optimal and reliable for calculating T2 maps in the human brain.

  16. 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.

  17. Metabolic Mapping of the Brain's Response to Visual Stimulation: Studies in Humans.

    ERIC Educational Resources Information Center

    Phelps, Michael E.; Kuhl, David E.

    1981-01-01

    Studies demonstrate increasing glucose metabolic rates in human primary (PVC) and association (AVC) visual cortex as complexity of visual scenes increase. AVC increased more rapidly with scene complexity than PVC and increased local metabolic activities above control subject with eyes closed; indicates wide range and metabolic reserve of visual…

  18. 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.

  19. 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

  20. 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.

  1. Brain dynamics during natural viewing conditions--a new guide for mapping connectivity in vivo.

    PubMed

    Bartels, Andreas; Zeki, Semir

    2005-01-15

    We describe here a new way of obtaining maps of connectivity in the human brain based on interregional correlations of blood oxygen level-dependent (BOLD) signal during natural viewing conditions. We propose that anatomical connections are reflected in BOLD signal correlations during natural brain dynamics. This may provide a powerful approach to chart connectivity, more so than that based on the 'resting state' of the human brain, and it may complement diffusion tensor imaging. Our approach relies on natural brain dynamics and is therefore experimentally unbiased and independent of hypothesis-driven, specialized stimuli. It has the advantage that natural viewing leads to considerably stronger cortical activity than rest, thus facilitating detection of weaker connections. To validate our technique, we used functional magnetic resonance imaging (fMRI) to record BOLD signal while volunteers freely viewed a movie that was interrupted by resting periods. We used independent component analysis (ICA) to segregate cortical areas before characterizing the dynamics of their BOLD signal during free viewing and rest. Natural viewing and rest each revealed highly specific correlation maps, which reflected known anatomical connections. Examples are homologous regions in visual and auditory cortices in the two hemispheres and the language network consisting of Wernicke's area, Broca's area, and a premotor region. Correlations between regions known to be directly connected were always substantially higher than between nonconnected regions. Furthermore, compared to rest, natural viewing specifically increased correlations between anatomically connected regions while it decreased correlations between nonconnected regions. Our findings therefore demonstrate that natural viewing conditions lead to particularly specific interregional correlations and thus provide a powerful environment to reveal anatomical connectivity in vivo.

  2. Studying variability in human brain aging in a population-based German cohort-rationale and design of 1000BRAINS.

    PubMed

    Caspers, Svenja; Moebus, Susanne; Lux, Silke; Pundt, Noreen; Schütz, Holger; Mühleisen, Thomas W; Gras, Vincent; Eickhoff, Simon B; Romanzetti, Sandro; Stöcker, Tony; Stirnberg, Rüdiger; Kirlangic, Mehmet E; Minnerop, Martina; Pieperhoff, Peter; Mödder, Ulrich; Das, Samir; Evans, Alan C; Jöckel, Karl-Heinz; Erbel, Raimund; Cichon, Sven; Nöthen, Markus M; Sturma, Dieter; Bauer, Andreas; Jon Shah, N; Zilles, Karl; Amunts, Katrin

    2014-01-01

    The ongoing 1000 brains study (1000BRAINS) is an epidemiological and neuroscientific investigation of structural and functional variability in the human brain during aging. The two recruitment sources are the 10-year follow-up cohort of the German Heinz Nixdorf Recall (HNR) Study, and the HNR MultiGeneration Study cohort, which comprises spouses and offspring of HNR subjects. The HNR is a longitudinal epidemiological investigation of cardiovascular risk factors, with a comprehensive collection of clinical, laboratory, socioeconomic, and environmental data from population-based subjects aged 45-75 years on inclusion. HNR subjects underwent detailed assessments in 2000, 2006, and 2011, and completed annual postal questionnaires on health status. 1000BRAINS accesses these HNR data and applies a separate protocol comprising: neuropsychological tests of attention, memory, executive functions and language; examination of motor skills; ratings of personality, life quality, mood and daily activities; analysis of laboratory and genetic data; and state-of-the-art magnetic resonance imaging (MRI, 3 Tesla) of the brain. The latter includes (i) 3D-T1- and 3D-T2-weighted scans for structural analyses and myelin mapping; (ii) three diffusion imaging sequences optimized for diffusion tensor imaging, high-angular resolution diffusion imaging for detailed fiber tracking and for diffusion kurtosis imaging; (iii) resting-state and task-based functional MRI; and (iv) fluid-attenuated inversion recovery and MR angiography for the detection of vascular lesions and the mapping of white matter lesions. The unique design of 1000BRAINS allows: (i) comprehensive investigation of various influences including genetics, environment and health status on variability in brain structure and function during aging; and (ii) identification of the impact of selected influencing factors on specific cognitive subsystems and their anatomical correlates.

  3. Spatio-Temporal Brain Mapping of Motion-Onset VEPs Combined with fMRI and Retinotopic Maps

    PubMed Central

    Pitzalis, Sabrina; Strappini, Francesca; De Gasperis, Marco; Bultrini, Alessandro; Di Russo, Francesco

    2012-01-01

    Neuroimaging studies have identified several motion-sensitive visual areas in the human brain, but the time course of their activation cannot be measured with these techniques. In the present study, we combined electrophysiological and neuroimaging methods (including retinotopic brain mapping) to determine the spatio-temporal profile of motion-onset visual evoked potentials for slow and fast motion stimuli and to localize its neural generators. We found that cortical activity initiates in the primary visual area (V1) for slow stimuli, peaking 100 ms after the onset of motion. Subsequently, activity in the mid-temporal motion-sensitive areas, MT+, peaked at 120 ms, followed by peaks in activity in the more dorsal area, V3A, at 160 ms and the lateral occipital complex at 180 ms. Approximately 250 ms after stimulus onset, activity fast motion stimuli was predominant in area V6 along the parieto-occipital sulcus. Finally, at 350 ms (100 ms after the motion offset) brain activity was visible again in area V1. For fast motion stimuli, the spatio-temporal brain pattern was similar, except that the first activity was detected at 70 ms in area MT+. Comparing functional magnetic resonance data for slow vs. fast motion, we found signs of slow-fast motion stimulus topography along the posterior brain in at least three cortical regions (MT+, V3A and LOR). PMID:22558222

  4. Optoacoustic mapping of cerebral blood oxygenation in humans

    NASA Astrophysics Data System (ADS)

    Petrov, Yuriy; Prough, Donald S.; Petrov, Irene Y.; Richardson, C. Joan; Fonseca, Rafael A.; Robertson, Claudia S.; Esenaliev, Rinat O.

    2017-03-01

    Noninvasive, transcranial mapping, monitoring, and imaging are highly important for detection and management of cerebral abnormalities and neuroscience research. Mapping, imaging, and monitoring of cerebral blood oxygenation are necessary for diagnostics and management of patients with traumatic brain injury, stroke, and other neurological conditions. We proposed to use optoacoustic technology for noninvasive, transcranial monitoring and imaging. In this work, we developed optoacoustic systems for mapping of cerebral blood oxygenation in humans and tested them in adults and neonates. The systems provide noninvasive, transcranial optoacoustic measurements in the transmission (forward) and reflection (backward) modes in the near infrared spectral range. Novel, ultra-sensitive probes were built for detection of optoacoustic signals and measurement of blood oxygenation in neonates and adults. Cerebral oxygenation was measured at different lateral sites from the superior sagittal sinus (SSS), a large central cerebral vein, located immediately beneath the midline of the human skull. In neonates, cerebral oxygenation was measured through open anterior and posterior fontanelles. Optoacoustic signal detection at different locations allowed for mapping of cerebral blood oxygenation. Our future studies will be focused on 3D mapping of cerebral blood oxygenation.

  5. Altered metabolomic-genomic signature: A potential noninvasive biomarker of epilepsy.

    PubMed

    Wu, Helen C; Dachet, Fabien; Ghoddoussi, Farhad; Bagla, Shruti; Fuerst, Darren; Stanley, Jeffrey A; Galloway, Matthew P; Loeb, Jeffrey A

    2017-09-01

    This study aimed to identify noninvasive biomarkers of human epilepsy that can reliably detect and localize epileptic brain regions. Having noninvasive biomarkers would greatly enhance patient diagnosis, patient monitoring, and novel therapy development. At the present time, only surgically invasive, direct brain recordings are capable of detecting these regions with precision, which severely limits the pace and scope of both clinical management and research progress in epilepsy. We compared high versus low or nonspiking regions in nine medically intractable epilepsy surgery patients by performing integrated metabolomic-genomic-histological analyses of electrically mapped human cortical regions using high-resolution magic angle spinning proton magnetic resonance spectroscopy, cDNA microarrays, and histological analysis. We found a highly consistent and predictive metabolite logistic regression model with reduced lactate and increased creatine plus phosphocreatine and choline, suggestive of a chronically altered metabolic state in epileptic brain regions. Linking gene expression, cellular, and histological differences to these key metabolites using a hierarchical clustering approach predicted altered metabolic vascular coupling in the affected regions. Consistently, these predictions were validated histologically, showing both neovascularization and newly discovered, millimeter-sized microlesions. Using a systems biology approach on electrically mapped human cortex provides new evidence for spatially segregated, metabolic derangements in both neurovascular and synaptic architecture in human epileptic brain regions that could be a noninvasively detectable biomarker of epilepsy. These findings both highlight the immense power of a systems biology approach and identify a potentially important role that magnetic resonance spectroscopy can play in the research and clinical management of epilepsy. Wiley Periodicals, Inc. © 2017 International League Against Epilepsy.

  6. Data Mining in Cyber Operations

    DTIC Science & Technology

    2014-07-01

    information processing units intended to mimic the network of neurons in the human brain for performing pattern recognition  Self- organizing maps (SOM...patterns are mined from in order to influence the learning model . An exploratory attack does not alter the training process , but rather uses other...New Jersey: Prentice Hall. 21) Kohonen, T. (1982). Self- organized formation of topologically correct feature maps. Biological Cybernetics , 43, 59–69

  7. Why Fight the Enemy That You Can Reprogram

    DTIC Science & Technology

    2010-02-17

    2: A good map will get you there Since humans developed self awareness, there has been an interest in knowing how the brain works, how to fix the...2 Section 2: A good map will get you there...and essential asset for the commander than any gift for cunning.” 2 Throughout history, military leaders tried to get “into the head” of their

  8. A Unique Procedure to Identify Cell Surface Markers Through a Spherical Self-Organizing Map Applied to DNA Microarray Analysis.

    PubMed

    Sugii, Yuh; Kasai, Tomonari; Ikeda, Masashi; Vaidyanath, Arun; Kumon, Kazuki; Mizutani, Akifumi; Seno, Akimasa; Tokutaka, Heizo; Kudoh, Takayuki; Seno, Masaharu

    2016-01-01

    To identify cell-specific markers, we designed a DNA microarray platform with oligonucleotide probes for human membrane-anchored proteins. Human glioma cell lines were analyzed using microarray and compared with normal and fetal brain tissues. For the microarray analysis, we employed a spherical self-organizing map, which is a clustering method suitable for the conversion of multidimensional data into two-dimensional data and displays the relationship on a spherical surface. Based on the gene expression profile, the cell surface characteristics were successfully mirrored onto the spherical surface, thereby distinguishing normal brain tissue from the disease model based on the strength of gene expression. The clustered glioma-specific genes were further analyzed by polymerase chain reaction procedure and immunocytochemical staining of glioma cells. Our platform and the following procedure were successfully demonstrated to categorize the genes coding for cell surface proteins that are specific to glioma cells. Our assessment demonstrates that a spherical self-organizing map is a valuable tool for distinguishing cell surface markers and can be employed in marker discovery studies for the treatment of cancer.

  9. Baby Brain Map

    MedlinePlus

    ... a Member Home Resources & Services Professional Resource Baby Brain Map Mar 17, 2016 The Brain Map was adapted in 2006 by ZERO TO ... supports Adobe Flash Player. To view the Baby Brain Map, please visit this page on a browser ...

  10. A Novel Perspective on Dopaminergic Processing of Human Addiction.

    PubMed

    Badgaiyan, Rajendra D

    2013-01-01

    Converging evidence from clinical, animal, and neuroimaging experiments suggests that the addictive behavior is associated with dysregulated dopamine neurotransmission. The precise role of dopamine in establishment and maintenance of addiction however is unclear. In this context animal studies on the brain reward system and the associative memory processing provide a novel insight. It was shown that both processing involve dopamine neurotransmission and both are disrupted in addiction. These findings indicate that dysregulated dopamine neurotransmission alters the brain processing of not only the reward system but also that of the memory of association between an addictive substance and reward. These alterations lead to maladaptive motivational behavior leading to chemical dependency. This concept however is based mostly on the data obtained in laboratory animals because of the paucity of human data. Due to lack of a reliable technique to study neurotransmission in the live human brain, it has been a problem to study the role of dopamine in human volunteers. A recently developed dynamic molecular imaging technique however, provides an opportunity to study these concepts in human volunteers because the technique allows detection, mapping and measurement of dopamine released in the live human brain during task performance.

  11. Evaluation of MRI sequences for quantitative T1 brain mapping

    NASA Astrophysics Data System (ADS)

    Tsialios, P.; Thrippleton, M.; Glatz, A.; Pernet, C.

    2017-11-01

    T1 mapping constitutes a quantitative MRI technique finding significant application in brain imaging. It allows evaluation of contrast uptake, blood perfusion, volume, providing a more specific biomarker of disease progression compared to conventional T1-weighted images. While there are many techniques for T1-mapping there is a wide range of reported T1-values in tissues, raising the issue of protocols reproducibility and standardization. The gold standard for obtaining T1-maps is based on acquiring IR-SE sequence. Widely used alternative sequences are IR-SE-EPI, VFA (DESPOT), DESPOT-HIFI and MP2RAGE that speed up scanning and fitting procedures. A custom MRI phantom was used to assess the reproducibility and accuracy of the different methods. All scans were performed using a 3T Siemens Prisma scanner. The acquired data processed using two different codes. The main difference was observed for VFA (DESPOT) which grossly overestimated T1 relaxation time by 214 ms [126 270] compared to the IR-SE sequence. MP2RAGE and DESPOT-HIFI sequences gave slightly shorter time than IR-SE (~20 to 30ms) and can be considered as alternative and time-efficient methods for acquiring accurate T1 maps of the human brain, while IR-SE-EPI gave identical result, at a cost of a lower image quality.

  12. Identification of prefrontal cortex (BA10) activation while performing Stroop test using diffuse optical tomography

    NASA Astrophysics Data System (ADS)

    Khadka, Sabin; Chityala, Srujan R.; Tian, Fenghua; Liu, Hanli

    2011-03-01

    Stroop test is commonly used as a behavior-testing tool for psychological examinations that are related to attention and cognitive control of the human brain. Studies have shown activations in Broadmann area 10 (BA10) of prefrontal cortex (PFC) during attention and cognitive process. The use of diffuse optical tomography (DOT) for human brain mapping is becoming more prevalent. In this study we expect to find neural correlates between the performed cognitive tasks and hemodynamic signals detected by a DOT system. Our initial observation showed activation of oxy-hemoglobin concentration in BA 10, which is consistent with some results seen by positron emission tomography (PET) and functional magnetic resonance imaging (fMRI). Our study demonstrates the possibility of combining DOT with Stroop test to quantitatively investigate cognitive functions of the human brain at the prefrontal cortex.

  13. Functional brain microstate predicts the outcome in a visuospatial working memory task.

    PubMed

    Muthukrishnan, Suriya-Prakash; Ahuja, Navdeep; Mehta, Nalin; Sharma, Ratna

    2016-11-01

    Humans have limited capacity of processing just up to 4 integrated items of information in the working memory. Thus, it is inevitable to commit more errors when challenged with high memory loads. However, the neural mechanisms that determine the accuracy of response at high memory loads still remain unclear. High temporal resolution of Electroencephalography (EEG) technique makes it the best tool to resolve the temporal dynamics of brain networks. EEG-defined microstate is the quasi-stable scalp electrical potential topography that represents the momentary functional state of brain. Thus, it has been possible to assess the information processing currently performed by the brain using EEG microstate analysis. We hypothesize that the EEG microstate preceding the trial could determine its outcome in a visuospatial working memory (VSWM) task. Twenty-four healthy participants performed a high memory load VSWM task, while their brain activity was recorded using EEG. Four microstate maps were found to represent the functional brain state prior to the trials in the VSWM task. One pre-trial microstate map was found to determine the accuracy of subsequent behavioural response. The intracranial generators of the pre-trial microstate map that determined the response accuracy were localized to the visuospatial processing areas at bilateral occipital, right temporal and limbic cortices. Our results imply that the behavioural outcome in a VSWM task could be determined by the intensity of activation of memory representations in the visuospatial processing brain regions prior to the trial. Copyright © 2016 Elsevier B.V. All rights reserved.

  14. Evaluation of potential models for imprinted and nonimprinted components of human chromosome 15q11-q13 syndromes by fine-structure homology mapping in the mouse.

    PubMed Central

    Nicholls, R D; Gottlieb, W; Russell, L B; Davda, M; Horsthemke, B; Rinchik, E M

    1993-01-01

    Prader-Willi and Angelman syndromes are complex neurobehavioral contiguous gene syndromes whose expression depends on the unmasking of genomic imprinting for different genetic loci in human chromosome 15q11-q13. The homologous chromosomal region in the mouse genome has been fine-mapped by using interspecific (Mus spretus) crosses and overlapping, radiation-induced deletions to evaluate potential animal models for both imprinted and nonimprinted components of these syndromes. Four evolutionarily conserved sequences from human 15q11-q13, including two cDNAs from fetal brain (DN10, D15S12h; DN34, D15S9h-1), a microdissected clone (MN7; D15F37S1h) expressed in mouse brain, and the gene for the beta 3 subunit of the gamma-aminobutyric acid type A receptor (Gabrb3), were mapped in mouse chromosome 7 by analysis of deletions at the pink-eyed dilution (p) locus. Three of these loci are deleted in pre- and postnatally lethal p-locus mutations, which extend up to 5.5 +/- 1.7 centimorgans (cM) proximal to p; D15S9h-1, which maps 1.1 +/- 0.8 cM distal to p and is the mouse homolog of the human gene D15S9 (which shows a DNA methylation imprint), is not deleted in any of the p-locus deletion series. A transcript from the Gabrb3 gene, but not the transcript detected by MN7 at the D15F37S1h locus, is expressed in mice homozygous for the p6H deletion, which have an abnormal neurological phenotype. Furthermore, the Gabrb3 transcript is expressed equally well from the maternal or paternal chromosome 7 and, therefore, its expression is not imprinted in mouse brain. Deletions at the mouse p locus should serve as intermediate genetic reagents and models with which to analyze the genetics and etiology of individual components of human 15q11-q13 disorders. Images Fig. 1 Fig. 2 Fig. 4 Fig. 5 PMID:8095339

  15. 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

  16. Novel methodology to characterize electromagnetic exposure of the brain

    NASA Astrophysics Data System (ADS)

    Crespo-Valero, Pedro; Christopoulou, Maria; Zefferer, Marcel; Christ, Andreas; Achermann, Peter; Nikita, Konstantina S.; Kuster, Niels

    2011-01-01

    Due to the greatly non-uniform field distribution induced in brain tissues by radio frequency electromagnetic sources, the exposure of anatomical and functional regions of the brain may be a key issue in interpreting laboratory findings and epidemiological studies concerning endpoints related to the central nervous system. This paper introduces the Talairach atlas in characterization of the electromagnetic exposure of the brain. A hierarchical labeling scheme is mapped onto high-resolution human models. This procedure is fully automatic and allows identification of over a thousand different sites all over the brain. The electromagnetic absorption can then be extracted and interpreted in every region or combination of regions in the brain, depending on the characterization goals. The application examples show how this methodology enhances the dosimetry assessment of the brain based on results obtained by either finite difference time domain simulations or measurements delivered by test compliance dosimetry systems. Applications include, among others, the detailed dosimetric analysis of the exposure of the brain during cell phone use, improved design of exposure setups for human studies or medical diagnostic and therapeutic devices using electromagnetic fields or ultrasound.

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

    PubMed Central

    Barrett, H. Clark

    2012-01-01

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

  18. Interpreting fMRI data: maps, modules and dimensions

    PubMed Central

    Op de Beeck, Hans P.; Haushofer, Johannes; Kanwisher, Nancy G.

    2009-01-01

    Neuroimaging research over the past decade has revealed a detailed picture of the functional organization of the human brain. Here we focus on two fundamental questions that are raised by the detailed mapping of sensory and cognitive functions and illustrate these questions with findings from the object-vision pathway. First, are functionally specific regions that are located close together best understood as distinct cortical modules or as parts of a larger-scale cortical map? Second, what functional properties define each cortical map or module? We propose a model in which overlapping continuous maps of simple features give rise to discrete modules that are selective for complex stimuli. PMID:18200027

  19. Human brain atlas for automated region of interest selection in quantitative susceptibility mapping: application to determine iron content in deep gray matter structures

    PubMed Central

    Lim, Issel Anne L.; Faria, Andreia V.; Li, Xu; Hsu, Johnny T.C.; Airan, Raag D.; Mori, Susumu; van Zijl, Peter C. M.

    2013-01-01

    The purpose of this paper is to extend the single-subject Eve atlas from Johns Hopkins University, which currently contains diffusion tensor and T1-weighted anatomical maps, by including contrast based on quantitative susceptibility mapping. The new atlas combines a “deep gray matter parcellation map” (DGMPM) derived from a single-subject quantitative susceptibility map with the previously established “white matter parcellation map” (WMPM) from the same subject’s T1-weighted and diffusion tensor imaging data into an MNI coordinate map named the “Everything Parcellation Map in Eve Space,” also known as the “EvePM.” It allows automated segmentation of gray matter and white matter structures. Quantitative susceptibility maps from five healthy male volunteers (30 to 33 years of age) were coregistered to the Eve Atlas with AIR and Large Deformation Diffeomorphic Metric Mapping (LDDMM), and the transformation matrices were applied to the EvePM to produce automated parcellation in subject space. Parcellation accuracy was measured with a kappa analysis for the left and right structures of six deep gray matter regions. For multi-orientation QSM images, the Kappa statistic was 0.85 between automated and manual segmentation, with the inter-rater reproducibility Kappa being 0.89 for the human raters, suggesting “almost perfect” agreement between all segmentation methods. Segmentation seemed slightly more difficult for human raters on single-orientation QSM images, with the Kappa statistic being 0.88 between automated and manual segmentation, and 0.85 and 0.86 between human raters. Overall, this atlas provides a time-efficient tool for automated coregistration and segmentation of quantitative susceptibility data to analyze many regions of interest. These data were used to establish a baseline for normal magnetic susceptibility measurements for over 60 brain structures of 30- to 33-year-old males. Correlating the average susceptibility with age-based iron concentrations in gray matter structures measured by Hallgren and Sourander (1958) allowed interpolation of the average iron concentration of several deep gray matter regions delineated in the EvePM. PMID:23769915

  20. Global differential expression of genes located in the Down Syndrome Critical Region in normal human brain

    PubMed Central

    Montoya, Julio Cesar; Fajardo, Dianora; Peña, Angela; Sánchez, Adalberto; Domínguez, Martha C; Satizábal, José María

    2014-01-01

    Background: The information of gene expression obtained from databases, have made possible the extraction and analysis of data related with several molecular processes involving not only in brain homeostasis but its disruption in some neuropathologies; principally in Down syndrome and the Alzheimer disease. Objective: To correlate the levels of transcription of 19 genes located in the Down Syndrome Critical Region (DSCR) with their expression in several substructures of normal human brain. Methods: There were obtained expression profiles of 19 DSCR genes in 42 brain substructures, from gene expression values available at the database of the human brain of the Brain Atlas of the Allen Institute for Brain Sciences", (http://human.brain-map.org/). The co-expression patterns of DSCR genes in brain were calculated by using multivariate statistical methods. Results: Highest levels of gene expression were registered at caudate nucleus, nucleus accumbens and putamen among central areas of cerebral cortex. Increased expression levels of RCAN1 that encode by a protein involved in signal transduction process of the CNS were recorded for PCP4 that participates in the binding to calmodulin and TTC3; a protein that is associated with differentiation of neurons. That previously identified brain structures play a crucial role in the learning process, in different class of memory and in motor skills. Conclusion: The precise regulation of DSCR gene expression is crucial to maintain the brain homeostasis, especially in those areas with high levels of gene expression associated with a remarkable process of learning and cognition. PMID:25767303

  1. Data-driven analysis of functional brain interactions during free listening to music and speech.

    PubMed

    Fang, Jun; Hu, Xintao; Han, Junwei; Jiang, Xi; Zhu, Dajiang; Guo, Lei; Liu, Tianming

    2015-06-01

    Natural stimulus functional magnetic resonance imaging (N-fMRI) such as fMRI acquired when participants were watching video streams or listening to audio streams has been increasingly used to investigate functional mechanisms of the human brain in recent years. One of the fundamental challenges in functional brain mapping based on N-fMRI is to model the brain's functional responses to continuous, naturalistic and dynamic natural stimuli. To address this challenge, in this paper we present a data-driven approach to exploring functional interactions in the human brain during free listening to music and speech streams. Specifically, we model the brain responses using N-fMRI by measuring the functional interactions on large-scale brain networks with intrinsically established structural correspondence, and perform music and speech classification tasks to guide the systematic identification of consistent and discriminative functional interactions when multiple subjects were listening music and speech in multiple categories. The underlying premise is that the functional interactions derived from N-fMRI data of multiple subjects should exhibit both consistency and discriminability. Our experimental results show that a variety of brain systems including attention, memory, auditory/language, emotion, and action networks are among the most relevant brain systems involved in classic music, pop music and speech differentiation. Our study provides an alternative approach to investigating the human brain's mechanism in comprehension of complex natural music and speech.

  2. Methodological dimensions of transcranial brain stimulation with the electrical current in human.

    PubMed

    Rostami, Maryam; Golesorkhi, Mehrshad; Ekhtiari, Hamed

    2013-01-01

    Transcranial current stimulation (TCS) is a neuromodulation method in which the patient is exposed to a mild electric current (direct or alternating) at 1-2 mA, resulting in an increase or a decrease in the brain excitability. This modification in neural activities can be used as a method for functional human brain mapping with causal inferences. This method might also facilitate the treatments of many neuropsychiatric disorders based on its inexpensive, simple, safe, noninvasive, painless, semi-focal excitatory and inhibitory effects. Given this, a comparison amongst different brain stimulation modalities has been made to determine the potential advantages of the TCS method. In addition, considerable methodological details on using TCS in basic and clinical neuroscience studies in human subjects have been introduced. Technical characteristics of TCS devices and their related accessories with regard to safety concerns have also been well articulated. Finally, some TCS application opportunities have been emphasized, including its potential use in the near future.

  3. Diffusion Tensor Magnetic Resonance Imaging Strategies for Color Mapping of Human Brain Anatomy

    PubMed Central

    Boujraf, Saïd

    2018-01-01

    Background: A color mapping of fiber tract orientation using diffusion tensor imaging (DTI) can be prominent in clinical practice. The goal of this paper is to perform a comparative study of visualized diffusion anisotropy in the human brain anatomical entities using three different color-mapping techniques based on diffusion-weighted imaging (DWI) and DTI. Methods: The first technique is based on calculating a color map from DWIs measured in three perpendicular directions. The second technique is based on eigenvalues derived from the diffusion tensor. The last technique is based on three eigenvectors corresponding to sorted eigenvalues derived from the diffusion tensor. All magnetic resonance imaging measurements were achieved using a 1.5 Tesla Siemens Vision whole body imaging system. A single-shot DW echoplanar imaging sequence used a Stejskal–Tanner approach. Trapezoidal diffusion gradients are used. The slice orientation was transverse. The basic measurement yielded a set of 13 images. Each series consists of a single image without diffusion weighting, besides two DWIs for each of the next six noncollinear magnetic field gradient directions. Results: The three types of color maps were calculated consequently using the DWI obtained and the DTI. Indeed, we established an excellent similarity between the image data in the color maps and the fiber directions of known anatomical structures (e.g., corpus callosum and gray matter). Conclusions: In the meantime, rotationally invariant quantities such as the eigenvectors of the diffusion tensor reflected better, the real orientation found in the studied tissue. PMID:29928631

  4. Language Mapping in Awake Surgery: Report of Two Cases with Review of Language Networks.

    PubMed

    Lim, Liang Hooi; Idris, Zamzuri; Reza, Faruque; Wan Hassan, Wan Mohd Nazaruddin; Mukmin, Laila Abd; Abdullah, Jafri Malin

    2018-01-01

    The role of language in communication plays a crucial role in human development and function. In patients who have a surgical lesion at the functional language areas, surgery should be intricately planned to avoid incurring further morbidity. This normally requires extensive functional and anatomical mappings of the brain to identify regions that are involved in language processing and production. In our case report, regions of the brain that are important for language functions were studied before surgery by employing (a) extraoperative methods such as functional magnetic resonance imaging, transmagnetic stimulation, and magnetoencephalography; (b) during the surgery by utilizing intraoperative awake surgical methods such as an intraoperative electrical stimulation; and (c) a two-stage surgery, in which electrical stimulation and first mapping are made thoroughly in the ward before second remapping during surgery. The extraoperative methods before surgery can guide the neurosurgeon to localize the functional language regions and tracts preoperatively. This will be confirmed using single-stage intraoperative electrical brain stimulation during surgery or a two-stage electrical brain stimulation before and during surgery. Here, we describe two cases in whom one has a superficial lesion and another a deep-seated lesion at language-related regions, in which language mapping was done to preserve its function. Additional review on the neuroanatomy of language regions, language network, and its impairment was also described.

  5. Analysis of neoplastic lesions in magnetic resonance imaging using self-organizing maps.

    PubMed

    Mei, Paulo Afonso; de Carvalho Carneiro, Cleyton; Fraser, Stephen J; Min, Li Li; Reis, Fabiano

    2015-12-15

    To provide an improved method for the identification and analysis of brain tumors in MRI scans using a semi-automated computational approach, that has the potential to provide a more objective, precise and quantitatively rigorous analysis, compared to human visual analysis. Self-Organizing Maps (SOM) is an unsupervised, exploratory data analysis tool, which can automatically domain an image into selfsimilar regions or clusters, based on measures of similarity. It can be used to perform image-domain of brain tissue on MR images, without prior knowledge. We used SOM to analyze T1, T2 and FLAIR acquisitions from two MRI machines in our service from 14 patients with brain tumors confirmed by biopsies--three lymphomas, six glioblastomas, one meningioma, one ganglioglioma, two oligoastrocytomas and one astrocytoma. The SOM software was used to analyze the data from the three image acquisitions from each patient and generated a self-organized map for each containing 25 clusters. Damaged tissue was separated from the normal tissue using the SOM technique. Furthermore, in some cases it allowed to separate different areas from within the tumor--like edema/peritumoral infiltration and necrosis. In lesions with less precise boundaries in FLAIR, the estimated damaged tissue area in the resulting map appears bigger. Our results showed that SOM has the potential to be a powerful MR imaging analysis technique for the assessment of brain tumors. Copyright © 2015. Published by Elsevier B.V.

  6. Dynamic patterns of cortical expansion during folding of the preterm human brain.

    PubMed

    Garcia, Kara E; Robinson, Emma C; Alexopoulos, Dimitrios; Dierker, Donna L; Glasser, Matthew F; Coalson, Timothy S; Ortinau, Cynthia M; Rueckert, Daniel; Taber, Larry A; Van Essen, David C; Rogers, Cynthia E; Smyser, Christopher D; Bayly, Philip V

    2018-03-20

    During the third trimester of human brain development, the cerebral cortex undergoes dramatic surface expansion and folding. Physical models suggest that relatively rapid growth of the cortical gray matter helps drive this folding, and structural data suggest that growth may vary in both space (by region on the cortical surface) and time. In this study, we propose a unique method to estimate local growth from sequential cortical reconstructions. Using anatomically constrained multimodal surface matching (aMSM), we obtain accurate, physically guided point correspondence between younger and older cortical reconstructions of the same individual. From each pair of surfaces, we calculate continuous, smooth maps of cortical expansion with unprecedented precision. By considering 30 preterm infants scanned two to four times during the period of rapid cortical expansion (28-38 wk postmenstrual age), we observe significant regional differences in growth across the cortical surface that are consistent with the emergence of new folds. Furthermore, these growth patterns shift over the course of development, with noninjured subjects following a highly consistent trajectory. This information provides a detailed picture of dynamic changes in cortical growth, connecting what is known about patterns of development at the microscopic (cellular) and macroscopic (folding) scales. Since our method provides specific growth maps for individual brains, we are also able to detect alterations due to injury. This fully automated surface analysis, based on tools freely available to the brain-mapping community, may also serve as a useful approach for future studies of abnormal growth due to genetic disorders, injury, or other environmental variables.

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

    PubMed Central

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

    2015-01-01

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

  8. Distribution of vesicular glutamate transporters in the human brain

    PubMed Central

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

    2015-01-01

    Glutamate is the major excitatory transmitter in the brain. Vesicular glutamate transporters (VGLUT1-3) are responsible for uploading glutamate into synaptic vesicles. VGLUT1 and VGLUT2 are considered as specific markers of canonical glutamatergic neurons, while VGLUT3 is found in neurons previously shown to use other neurotransmitters than glutamate. Although there exists a rich literature on the localization of these glutamatergic markers in the rodent brain, little is currently known about the distribution of VGLUT1-3 in the human brain. In the present study, using subtype specific probes and antisera, we examined the localization of the three vesicular glutamate transporters in the human brain by in situ hybridization, immunoautoradiography and immunohistochemistry. We found that the VGLUT1 transcript was highly expressed in the cerebral cortex, hippocampus and cerebellum, whereas VGLUT2 mRNA was mainly found in the thalamus and brainstem. VGLUT3 mRNA was localized in scarce neurons within the cerebral cortex, hippocampus, striatum and raphe nuclei. Following immunoautoradiographic labeling, intense VGLUT1- and VGLUT2-immunoreactivities were observed in all regions investigated (cerebral cortex, hippocampus, caudate-putamen, cerebellum, thalamus, amygdala, substantia nigra, raphe) while VGLUT3 was absent from the thalamus and cerebellum. This extensive mapping of VGLUT1-3 in human brain reveals distributions that correspond for the most part to those previously described in rodent brains. PMID:25798091

  9. Distribution of vesicular glutamate transporters in the human brain.

    PubMed

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

    2015-01-01

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

  10. 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.

  11. Simultaneous mapping of water shift and B1 (WASABI)-Application to field-Inhomogeneity correction of CEST MRI data.

    PubMed

    Schuenke, Patrick; Windschuh, Johannes; Roeloffs, Volkert; Ladd, Mark E; Bachert, Peter; Zaiss, Moritz

    2017-02-01

    Together with the development of MRI contrasts that are inherently small in their magnitude, increased magnetic field accuracy is also required. Hence, mapping of the static magnetic field (B 0 ) and the excitation field (B 1 ) is not only important to feedback shim algorithms, but also for postprocess contrast-correction procedures. A novel field-inhomogeneity mapping method is presented that allows simultaneous mapping of the water shift and B 1 (WASABI) using an off-resonant rectangular preparation pulse. The induced Rabi oscillations lead to a sinc-like spectrum in the frequency-offset dimension and allow for determination of B 0 by its symmetry axis and of B 1 by its oscillation frequency. Stability of the WASABI method with regard to the influences of T 1 , T 2 , magnetization transfer, and repetition time was investigated and its convergence interval was verified. B 0 and B 1 maps obtained simultaneously by means of WASABI in the human brain at 3 T and 7 T can compete well with maps obtained by standard methods. Finally, the method was applied successfully for B 0 and B 1 correction of chemical exchange saturation transfer MRI (CEST-MRI) data of the human brain. The proposed WASABI method yields a novel simultaneous B 0 and B 1 mapping within 1 min that is robust and easy to implement. Magn Reson Med 77:571-580, 2017. © 2016 International Society for Magnetic Resonance in Medicine. © 2016 International Society for Magnetic Resonance in Medicine.

  12. Magnetic Tunnel Junction Mimics Stochastic Cortical Spiking Neurons

    NASA Astrophysics Data System (ADS)

    Sengupta, Abhronil; Panda, Priyadarshini; Wijesinghe, Parami; Kim, Yusung; Roy, Kaushik

    2016-07-01

    Brain-inspired computing architectures attempt to mimic the computations performed in the neurons and the synapses in the human brain in order to achieve its efficiency in learning and cognitive tasks. In this work, we demonstrate the mapping of the probabilistic spiking nature of pyramidal neurons in the cortex to the stochastic switching behavior of a Magnetic Tunnel Junction in presence of thermal noise. We present results to illustrate the efficiency of neuromorphic systems based on such probabilistic neurons for pattern recognition tasks in presence of lateral inhibition and homeostasis. Such stochastic MTJ neurons can also potentially provide a direct mapping to the probabilistic computing elements in Belief Networks for performing regenerative tasks.

  13. Morphology, morphometry and probability mapping of the pars opercularis of the inferior frontal gyrus: an in vivo MRI analysis.

    PubMed

    Tomaiuolo, F; MacDonald, J D; Caramanos, Z; Posner, G; Chiavaras, M; Evans, A C; Petrides, M

    1999-09-01

    The pars opercularis occupies the posterior part of the inferior frontal gyrus. Electrical stimulation or damage of this region interferes with language production. The present study investigated the morphology and morphometry of the pars opercularis in 108 normal adult human cerebral hemispheres by means of magnetic resonance imaging. The brain images were transformed into a standardized proportional steoreotaxic space (i.e. that of Talairach and Tournoux) in order to minimize interindividual brain size variability. There was considerable variability in the shape and location of the pars opercularis across brains and between cerebral hemispheres. There was no significant difference or correlation between left and right hemisphere grey matter volumes. There was also no significant difference between sex and side of asymmetry of the pars opercularis. A probability map of the pars opercularis was constructed by averaging its location and extent in each individual normalized brain into Talairach space to aid in localization of activity changes in functional neuroimaging studies.

  14. Mapping Epileptic Activity: Sources or Networks for the Clinicians?

    PubMed Central

    Pittau, Francesca; Mégevand, Pierre; Sheybani, Laurent; Abela, Eugenio; Grouiller, Frédéric; Spinelli, Laurent; Michel, Christoph M.; Seeck, Margitta; Vulliemoz, Serge

    2014-01-01

    Epileptic seizures of focal origin are classically considered to arise from a focal epileptogenic zone and then spread to other brain regions. This is a key concept for semiological electro-clinical correlations, localization of relevant structural lesions, and selection of patients for epilepsy surgery. Recent development in neuro-imaging and electro-physiology and combinations, thereof, have been validated as contributory tools for focus localization. In parallel, these techniques have revealed that widespread networks of brain regions, rather than a single epileptogenic region, are implicated in focal epileptic activity. Sophisticated multimodal imaging and analysis strategies of brain connectivity patterns have been developed to characterize the spatio-temporal relationships within these networks by combining the strength of both techniques to optimize spatial and temporal resolution with whole-brain coverage and directional connectivity. In this paper, we review the potential clinical contribution of these functional mapping techniques as well as invasive electrophysiology in human beings and animal models for characterizing network connectivity. PMID:25414692

  15. EEG mapping and low-resolution brain electromagnetic tomography (LORETA) in diagnosis and therapy of psychiatric disorders: evidence for a key-lock principle.

    PubMed

    Saletu, Bernd; Anderer, Peter; Saletu-Zyhlarz, Gerda M; Pascual-Marqui, Roberto D

    2005-04-01

    Different psychiatric disorders, such as schizophrenia with predominantly positive and negative symptomatology, major depression, generalized anxiety disorder, agoraphobia, obsessive-compulsive disorder, multi-infarct dementia, senile dementia of the Alzheimer type and alcohol dependence, show EEG maps that differ statistically both from each other and from normal controls. Representative drugs of the main psychopharmacological classes, such as sedative and non-sedative neuroleptics and antidepressants, tranquilizers, hypnotics, psychostimulants and cognition-enhancing drugs, induce significant and typical changes to normal human brain function, which in many variables are opposite to the above-mentioned differences between psychiatric patients and normal controls. Thus, by considering these differences between psychotropic drugs and placebo in normal subjects, as well as between mental disorder patients and normal controls, it may be possible to choose the optimum drug for a specific patient according to a key-lock principle, since the drug should normalize the deviant brain function. This is supported by 3-dimensional low-resolution brain electromagnetic tomography (LORETA), which identifies regions within the brain that are affected by psychiatric disorders and psychopharmacological substances.

  16. Detection and mapping of delays in early cortical folding derived from in utero MRI

    NASA Astrophysics Data System (ADS)

    Habas, Piotr A.; Rajagopalan, Vidya; Scott, Julia A.; Kim, Kio; Roosta, Ahmad; Rousseau, Francois; Barkovich, A. James; Glenn, Orit A.; Studholme, Colin

    2011-03-01

    Understanding human brain development in utero and detecting cortical abnormalities related to specific clinical conditions is an important area of research. In this paper, we describe and evaluate methodology for detection and mapping of delays in early cortical folding from population-based studies of fetal brain anatomies imaged in utero. We use a general linear modeling framework to describe spatiotemporal changes in curvature of the developing brain and explore the ability to detect and localize delays in cortical folding in the presence of uncertainty in estimation of the fetal age. We apply permutation testing to examine which regions of the brain surface provide the most statistical power to detect a given folding delay at a given developmental stage. The presented methodology is evaluated using MR scans of fetuses with normal brain development and gestational ages ranging from 20.57 to 27.86 weeks. This period is critical in early cortical folding and the formation of the primary and secondary sulci. Finally, we demonstrate a clinical application of the framework for detection and localization of folding delays in fetuses with isolated mild ventriculomegaly.

  17. Dynamic multi-coil technique (DYNAMITE) shimming for echo-planar imaging of the human brain at 7 Tesla.

    PubMed

    Juchem, Christoph; Umesh Rudrapatna, S; Nixon, Terence W; de Graaf, Robin A

    2015-01-15

    Gradient-echo echo-planar imaging (EPI) is the primary method of choice in functional MRI and other methods relying on fast MRI to image brain activation and connectivity. However, the high susceptibility of EPI towards B0 magnetic field inhomogeneity poses serious challenges. Conventional magnetic field shimming with low-order spherical harmonic (SH) functions is capable of compensating shallow field distortions, but performs poorly for global brain shimming or on specific areas with strong susceptibility-induced B0 distortions such as the prefrontal cortex (PFC). Excellent B0 homogeneity has been demonstrated recently in the human brain at 7 Tesla with the DYNAmic Multi-coIl TEchnique (DYNAMITE) for magnetic field shimming (J Magn Reson (2011) 212:280-288). Here, we report the benefits of DYNAMITE shimming for multi-slice EPI and T2* mapping. A standard deviation of 13Hz was achieved for the residual B0 distribution in the human brain at 7 Tesla with DYNAMITE shimming and was 60% lower compared to conventional shimming that employs static zero through third order SH shapes. The residual field inhomogeneity with SH shimming led to an average 8mm shift at acquisition parameters commonly used for fMRI and was reduced to 1.5-3mm with DYNAMITE shimming. T2* values obtained from the prefrontal and temporal cortices with DYNAMITE shimming were 10-50% longer than those measured with SH shimming. The reduction of the confounding macroscopic B0 field gradients with DYNAMITE shimming thereby promises improved access to the relevant microscopic T2* effects. The combination of high spatial resolution and DYNAMITE shimming allows largely artifact-free EPI and T2* mapping throughout the brain, including prefrontal and temporal lobe areas. DYNAMITE shimming is expected to critically benefit a wide range of MRI applications that rely on excellent B0 magnetic field conditions including EPI-based fMRI to study various cognitive processes and assessing large-scale brain connectivity in vivo. As such, DYNAMITE shimming has the potential to replace conventional SH shim systems in human MR scanners. Copyright © 2014 Elsevier Inc. All rights reserved.

  18. Dynamic Multi-Coil Technique (DYNAMITE) Shimming for Echo-Planar Imaging of the Human Brain at 7 Tesla

    PubMed Central

    Juchem, Christoph; Rudrapatna, S. Umesh; Nixon, Terence W.; de Graaf, Robin A.

    2014-01-01

    Gradient-echo echo-planar imaging (EPI) is the primary method of choice in functional MRI and other methods relying on fast MRI to image brain activation and connectivity. However, the high susceptibility of EPI towards B0 magnetic field inhomogeneity poses serious challenges. Conventional magnetic field shimming with low-order spherical harmonic (SH) functions is capable of compensating shallow field distortions, but performs poorly for global brain shimming or on specific areas with strong susceptibility-induced B0 distortions such as the prefrontal cortex (PFC). Excellent B0 homogeneity has been demonstrated recently in the human brain at 7 Tesla with the DYNAmic Multi-coIl TEchnique (DYNAMITE) for magnetic field shimming (Juchem et al., J Magn Reson (2011) 212:280-288). Here, we report the benefits of DYNAMITE shimming for multi-slice EPI and T2* mapping. A standard deviation of 13 Hz was achieved for the residual B0 distribution in the human brain at 7 Tesla with DYNAMITE shimming and was 60% lower compared to conventional shimming that employs static zero through third order SH shapes. The residual field inhomogeneity with SH shimming led to an average 8 mm shift at acquisition parameters commonly used for fMRI and was reduced to 1.5-3 mm with DYNAMITE shimming. T2* values obtained from the prefrontal and temporal cortices with DYNAMITE shimming were 10-50% longer than those measured with SH shimming. The reduction of the confounding macroscopic B0 field gradients with DYNAMITE shimming thereby promises improved access to the relevant microscopic T2* effects. The combination of high spatial resolution and DYNAMITE shimming allows largely artifact-free EPI and T2* mapping throughout the brain, including prefrontal and temporal lobe areas. DYNAMITE shimming is expected to critically benefit a wide range of MRI applications that rely on excellent B0 magnetic field conditions including EPI-based fMRI to study various cognitive processes and assessing large-scale brain connectivity in vivo. As such, DYNAMITE shimming has the potential to replace conventional SH shim systems in human MR scanners. PMID:25462795

  19. The BRAIN Initiative Cell Census Consortium: Lessons Learned toward Generating a Comprehensive Brain Cell Atlas.

    PubMed

    Ecker, Joseph R; Geschwind, Daniel H; Kriegstein, Arnold R; Ngai, John; Osten, Pavel; Polioudakis, Damon; Regev, Aviv; Sestan, Nenad; Wickersham, Ian R; Zeng, Hongkui

    2017-11-01

    A comprehensive characterization of neuronal cell types, their distributions, and patterns of connectivity is critical for understanding the properties of neural circuits and how they generate behaviors. Here we review the experiences of the BRAIN Initiative Cell Census Consortium, ten pilot projects funded by the U.S. BRAIN Initiative, in developing, validating, and scaling up emerging genomic and anatomical mapping technologies for creating a complete inventory of neuronal cell types and their connections in multiple species and during development. These projects lay the foundation for a larger and longer-term effort to generate whole-brain cell atlases in species including mice and humans. Copyright © 2017 Elsevier Inc. All rights reserved.

  20. L1 retrotransposons and somatic mosaicism in the brain.

    PubMed

    Richardson, Sandra R; Morell, Santiago; Faulkner, Geoffrey J

    2014-01-01

    Long interspersed element 1 (LINE-1 or L1) retrotransposons have generated one-third of the human genome, and their ongoing mobility is a source of inter- and intraindividual genetic diversity. Although retrotransposition in metazoans has long been considered a germline phenomenon, recent experiments using cultured cells, animal models, and human tissues have revealed extensive L1 mobilization in rodent and human neurons, as well as mobile element activity in the Drosophila brain. In this review, we evaluate the available evidence for L1 retrotransposition in the brain and discuss mechanisms that may regulate neuronal retrotransposition in vivo. We compare experimental strategies used to map de novo somatic retrotransposition events and present the optimal criteria to identify a somatic L1 insertion. Finally, we discuss the unresolved impact of L1-mediated somatic mosaicism upon normal neurobiology, as well as its potential to drive neurological disease.

  1. Inter-species activity correlations reveal functional correspondences between monkey and human brain areas

    PubMed Central

    Mantini, Dante; Hasson, Uri; Betti, Viviana; Perrucci, Mauro G.; Romani, Gian Luca; Corbetta, Maurizio; Orban, Guy A.; Vanduffel, Wim

    2012-01-01

    Evolution-driven functional changes in the primate brain are typically assessed by aligning monkey and human activation maps using cortical surface expansion models. These models use putative homologous areas as registration landmarks, assuming they are functionally correspondent. In cases where functional changes have occurred in an area, this assumption prohibits to reveal whether other areas may have assumed lost functions. Here we describe a method to examine functional correspondences across species. Without making spatial assumptions, we assess similarities in sensory-driven functional magnetic resonance imaging responses between monkey (Macaca mulatta) and human brain areas by means of temporal correlation. Using natural vision data, we reveal regions for which functional processing has shifted to topologically divergent locations during evolution. We conclude that substantial evolution-driven functional reorganizations have occurred, not always consistent with cortical expansion processes. This novel framework for evaluating changes in functional architecture is crucial to building more accurate evolutionary models. PMID:22306809

  2. Elemental mapping of biological samples using a scanning proton microprobe

    NASA Astrophysics Data System (ADS)

    Watt, F.; Grime, G. W.

    1988-03-01

    Elemental mapping using a scanning proton microprobe (SPM) can be a powerful technique for probing trace elements in biology, allowing complex interfaces to be studied in detail, identifying contamination and artefacts present in the specimen, and in certain circumstances obtaining indirect chemical information. Examples used to illustrate the advantages of the technique include the elemental mapping of growing pollen tubes, honey bee brain section, a mouse macrophage cell, human liver section exhibiting primary biliary cirrhosis, and the attack by a mildew fungus on a pea leaf.

  3. Template‐based field map prediction for rapid whole brain B0 shimming

    PubMed Central

    Shi, Yuhang; Vannesjo, S. Johanna; Miller, Karla L.

    2017-01-01

    Purpose In typical MRI protocols, time is spent acquiring a field map to calculate the shim settings for best image quality. We propose a fast template‐based field map prediction method that yields near‐optimal shims without measuring the field. Methods The template‐based prediction method uses prior knowledge of the B0 distribution in the human brain, based on a large database of field maps acquired from different subjects, together with subject‐specific structural information from a quick localizer scan. The shimming performance of using the template‐based prediction is evaluated in comparison to a range of potential fast shimming methods. Results Static B0 shimming based on predicted field maps performed almost as well as shimming based on individually measured field maps. In experimental evaluations at 7 T, the proposed approach yielded a residual field standard deviation in the brain of on average 59 Hz, compared with 50 Hz using measured field maps and 176 Hz using no subject‐specific shim. Conclusions This work demonstrates that shimming based on predicted field maps is feasible. The field map prediction accuracy could potentially be further improved by generating the template from a subset of subjects, based on parameters such as head rotation and body mass index. Magn Reson Med 80:171–180, 2018. © 2017 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 License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited. PMID:29193340

  4. 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

  5. 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.

  6. Assessing Variations in Areal Organization for the Intrinsic Brain: From Fingerprints to Reliability

    PubMed Central

    Xu, Ting; Opitz, Alexander; Craddock, R. Cameron; Wright, Margaret J.; Zuo, Xi-Nian; Milham, Michael P.

    2016-01-01

    Resting state fMRI (R-fMRI) is a powerful in-vivo tool for examining the functional architecture of the human brain. Recent studies have demonstrated the ability to characterize transitions between functionally distinct cortical areas through the mapping of gradients in intrinsic functional connectivity (iFC) profiles. To date, this novel approach has primarily been applied to iFC profiles averaged across groups of individuals, or in one case, a single individual scanned multiple times. Here, we used a publically available R-fMRI dataset, in which 30 healthy participants were scanned 10 times (10 min per session), to investigate differences in full-brain transition profiles (i.e., gradient maps, edge maps) across individuals, and their reliability. 10-min R-fMRI scans were sufficient to achieve high accuracies in efforts to “fingerprint” individuals based upon full-brain transition profiles. Regarding test–retest reliability, the image-wise intraclass correlation coefficient (ICC) was moderate, and vertex-level ICC varied depending on region; larger durations of data yielded higher reliability scores universally. Initial application of gradient-based methodologies to a recently published dataset obtained from twins suggested inter-individual variation in areal profiles might have genetic and familial origins. Overall, these results illustrate the utility of gradient-based iFC approaches for studying inter-individual variation in brain function. PMID:27600846

  7. Task-evoked brain functional magnetic susceptibility mapping by independent component analysis (χICA).

    PubMed

    Chen, Zikuan; Calhoun, Vince D

    2016-03-01

    Conventionally, independent component analysis (ICA) is performed on an fMRI magnitude dataset to analyze brain functional mapping (AICA). By solving the inverse problem of fMRI, we can reconstruct the brain magnetic susceptibility (χ) functional states. Upon the reconstructed χ dataspace, we propose an ICA-based brain functional χ mapping method (χICA) to extract task-evoked brain functional map. A complex division algorithm is applied to a timeseries of fMRI phase images to extract temporal phase changes (relative to an OFF-state snapshot). A computed inverse MRI (CIMRI) model is used to reconstruct a 4D brain χ response dataset. χICA is implemented by applying a spatial InfoMax ICA algorithm to the reconstructed 4D χ dataspace. With finger-tapping experiments on a 7T system, the χICA-extracted χ-depicted functional map is similar to the SPM-inferred functional χ map by a spatial correlation of 0.67 ± 0.05. In comparison, the AICA-extracted magnitude-depicted map is correlated with the SPM magnitude map by 0.81 ± 0.05. The understanding of the inferiority of χICA to AICA for task-evoked functional map is an ongoing research topic. For task-evoked brain functional mapping, we compare the data-driven ICA method with the task-correlated SPM method. In particular, we compare χICA with AICA for extracting task-correlated timecourses and functional maps. χICA can extract a χ-depicted task-evoked brain functional map from a reconstructed χ dataspace without the knowledge about brain hemodynamic responses. The χICA-extracted brain functional χ map reveals a bidirectional BOLD response pattern that is unavailable (or different) from AICA. Copyright © 2016 Elsevier B.V. All rights reserved.

  8. On testing for spatial correspondence between maps of human brain structure and function.

    PubMed

    Alexander-Bloch, Aaron F; Shou, Haochang; Liu, Siyuan; Satterthwaite, Theodore D; Glahn, David C; Shinohara, Russell T; Vandekar, Simon N; Raznahan, Armin

    2018-06-01

    A critical issue in many neuroimaging studies is the comparison between brain maps. Nonetheless, it remains unclear how one should test hypotheses focused on the overlap or spatial correspondence between two or more brain maps. This "correspondence problem" affects, for example, the interpretation of comparisons between task-based patterns of functional activation, resting-state networks or modules, and neuroanatomical landmarks. To date, this problem has been addressed with remarkable variability in terms of methodological approaches and statistical rigor. In this paper, we address the correspondence problem using a spatial permutation framework to generate null models of overlap by applying random rotations to spherical representations of the cortical surface, an approach for which we also provide a theoretical statistical foundation. We use this method to derive clusters of cognitive functions that are correlated in terms of their functional neuroatomical substrates. In addition, using publicly available data, we formally demonstrate the correspondence between maps of task-based functional activity, resting-state fMRI networks and gyral-based anatomical landmarks. We provide open-access code to implement the methods presented for two commonly-used tools for surface based cortical analysis (https://www.github.com/spin-test). This spatial permutation approach constitutes a useful advance over widely-used methods for the comparison of cortical maps, thereby opening new possibilities for the integration of diverse neuroimaging data. Copyright © 2018 Elsevier Inc. All rights reserved.

  9. Background field removal using a region adaptive kernel for quantitative susceptibility mapping of human brain

    NASA Astrophysics Data System (ADS)

    Fang, Jinsheng; Bao, Lijun; Li, Xu; van Zijl, Peter C. M.; Chen, Zhong

    2017-08-01

    Background field removal is an important MR phase preprocessing step for quantitative susceptibility mapping (QSM). It separates the local field induced by tissue magnetic susceptibility sources from the background field generated by sources outside a region of interest, e.g. brain, such as air-tissue interface. In the vicinity of air-tissue boundary, e.g. skull and paranasal sinuses, where large susceptibility variations exist, present background field removal methods are usually insufficient and these regions often need to be excluded by brain mask erosion at the expense of losing information of local field and thus susceptibility measures in these regions. In this paper, we propose an extension to the variable-kernel sophisticated harmonic artifact reduction for phase data (V-SHARP) background field removal method using a region adaptive kernel (R-SHARP), in which a scalable spherical Gaussian kernel (SGK) is employed with its kernel radius and weights adjustable according to an energy "functional" reflecting the magnitude of field variation. Such an energy functional is defined in terms of a contour and two fitting functions incorporating regularization terms, from which a curve evolution model in level set formation is derived for energy minimization. We utilize it to detect regions of with a large field gradient caused by strong susceptibility variation. In such regions, the SGK will have a small radius and high weight at the sphere center in a manner adaptive to the voxel energy of the field perturbation. Using the proposed method, the background field generated from external sources can be effectively removed to get a more accurate estimation of the local field and thus of the QSM dipole inversion to map local tissue susceptibility sources. Numerical simulation, phantom and in vivo human brain data demonstrate improved performance of R-SHARP compared to V-SHARP and RESHARP (regularization enabled SHARP) methods, even when the whole paranasal sinus regions are preserved in the brain mask. Shadow artifacts due to strong susceptibility variations in the derived QSM maps could also be largely eliminated using the R-SHARP method, leading to more accurate QSM reconstruction.

  10. Background field removal using a region adaptive kernel for quantitative susceptibility mapping of human brain.

    PubMed

    Fang, Jinsheng; Bao, Lijun; Li, Xu; van Zijl, Peter C M; Chen, Zhong

    2017-08-01

    Background field removal is an important MR phase preprocessing step for quantitative susceptibility mapping (QSM). It separates the local field induced by tissue magnetic susceptibility sources from the background field generated by sources outside a region of interest, e.g. brain, such as air-tissue interface. In the vicinity of air-tissue boundary, e.g. skull and paranasal sinuses, where large susceptibility variations exist, present background field removal methods are usually insufficient and these regions often need to be excluded by brain mask erosion at the expense of losing information of local field and thus susceptibility measures in these regions. In this paper, we propose an extension to the variable-kernel sophisticated harmonic artifact reduction for phase data (V-SHARP) background field removal method using a region adaptive kernel (R-SHARP), in which a scalable spherical Gaussian kernel (SGK) is employed with its kernel radius and weights adjustable according to an energy "functional" reflecting the magnitude of field variation. Such an energy functional is defined in terms of a contour and two fitting functions incorporating regularization terms, from which a curve evolution model in level set formation is derived for energy minimization. We utilize it to detect regions of with a large field gradient caused by strong susceptibility variation. In such regions, the SGK will have a small radius and high weight at the sphere center in a manner adaptive to the voxel energy of the field perturbation. Using the proposed method, the background field generated from external sources can be effectively removed to get a more accurate estimation of the local field and thus of the QSM dipole inversion to map local tissue susceptibility sources. Numerical simulation, phantom and in vivo human brain data demonstrate improved performance of R-SHARP compared to V-SHARP and RESHARP (regularization enabled SHARP) methods, even when the whole paranasal sinus regions are preserved in the brain mask. Shadow artifacts due to strong susceptibility variations in the derived QSM maps could also be largely eliminated using the R-SHARP method, leading to more accurate QSM reconstruction. Copyright © 2017. Published by Elsevier Inc.

  11. Neuroticism modulates brain visuo-vestibular and anxiety systems during a virtual rollercoaster task.

    PubMed

    Riccelli, Roberta; Indovina, Iole; Staab, Jeffrey P; Nigro, Salvatore; Augimeri, Antonio; Lacquaniti, Francesco; Passamonti, Luca

    2017-02-01

    Different lines of research suggest that anxiety-related personality traits may influence the visual and vestibular control of balance, although the brain mechanisms underlying this effect remain unclear. To our knowledge, this is the first functional magnetic resonance imaging (fMRI) study that investigates how individual differences in neuroticism and introversion, two key personality traits linked to anxiety, modulate brain regional responses and functional connectivity patterns during a fMRI task simulating self-motion. Twenty-four healthy individuals with variable levels of neuroticism and introversion underwent fMRI while performing a virtual reality rollercoaster task that included two main types of trials: (1) trials simulating downward or upward self-motion (vertical motion), and (2) trials simulating self-motion in horizontal planes (horizontal motion). Regional brain activity and functional connectivity patterns when comparing vertical versus horizontal motion trials were correlated with personality traits of the Five Factor Model (i.e., neuroticism, extraversion-introversion, openness, agreeableness, and conscientiousness). When comparing vertical to horizontal motion trials, we found a positive correlation between neuroticism scores and regional activity in the left parieto-insular vestibular cortex (PIVC). For the same contrast, increased functional connectivity between the left PIVC and right amygdala was also detected as a function of higher neuroticism scores. Together, these findings provide new evidence that individual differences in personality traits linked to anxiety are significantly associated with changes in the activity and functional connectivity patterns within visuo-vestibular and anxiety-related systems during simulated vertical self-motion. Hum Brain Mapp 38:715-726, 2017. © 2016 The Authors Human Brain Mapping Published by Wiley Periodicals, Inc. © 2016 The Authors Human Brain Mapping Published by Wiley Periodicals, Inc.

  12. The "social brain" is highly sensitive to the mere presence of social information: An automated meta-analysis and an independent study.

    PubMed

    Tso, Ivy F; Rutherford, Saige; Fang, Yu; Angstadt, Mike; Taylor, Stephan F

    2018-01-01

    How the human brain processes social information is an increasingly researched topic in psychology and neuroscience, advancing our understanding of basic human cognition and psychopathologies. Neuroimaging studies typically seek to isolate one specific aspect of social cognition when trying to map its neural substrates. It is unclear if brain activation elicited by different social cognitive processes and task instructions are also spontaneously elicited by general social information. In this study, we investigated whether these brain regions are evoked by the mere presence of social information using an automated meta-analysis and confirmatory data from an independent study of simple appraisal of social vs. non-social images. Results of 1,000 published fMRI studies containing the keyword of "social" were subject to an automated meta-analysis (http://neurosynth.org). To confirm that significant brain regions in the meta-analysis were driven by a social effect, these brain regions were used as regions of interest (ROIs) to extract and compare BOLD fMRI signals of social vs. non-social conditions in the independent study. The NeuroSynth results indicated that the dorsal and ventral medial prefrontal cortex, posterior cingulate cortex, bilateral amygdala, bilateral occipito-temporal junction, right fusiform gyrus, bilateral temporal pole, and right inferior frontal gyrus are commonly engaged in studies with a prominent social element. The social-non-social contrast in the independent study showed a strong resemblance to the NeuroSynth map. ROI analyses revealed that a social effect was credible in 9 out of the 11 NeuroSynth regions in the independent dataset. The findings support the conclusion that the "social brain" is highly sensitive to the mere presence of social information.

  13. White Matter Connectivity of the Thalamus Delineates the Functional Architecture of Competing Thalamocortical Systems

    PubMed Central

    O'Muircheartaigh, Jonathan; Keller, Simon S.; Barker, Gareth J.; Richardson, Mark P.

    2015-01-01

    There is an increasing awareness of the involvement of thalamic connectivity on higher level cortical functioning in the human brain. This is reflected by the influence of thalamic stimulation on cortical activity and behavior as well as apparently cortical lesion syndromes occurring as a function of small thalamic insults. Here, we attempt to noninvasively test the correspondence of structural and functional connectivity of the human thalamus using diffusion-weighted and resting-state functional MRI. Using a large sample of 102 adults, we apply tensor independent component analysis to diffusion MRI tractography data to blindly parcellate bilateral thalamus according to diffusion tractography-defined structural connectivity. Using resting-state functional MRI collected in the same subjects, we show that the resulting structurally defined thalamic regions map to spatially distinct, and anatomically predictable, whole-brain functional networks in the same subjects. Although there was significant variability in the functional connectivity patterns, the resulting 51 structural and functional patterns could broadly be reduced to a subset of 7 similar core network types. These networks were distinct from typical cortical resting-state networks. Importantly, these networks were distributed across the brain and, in a subset, map extremely well to known thalamocortico-basal-ganglial loops. PMID:25899706

  14. Brain Mapping in a Patient with Congenital Blindness – A Case for Multimodal Approaches

    PubMed Central

    Roland, Jarod L.; Hacker, Carl D.; Breshears, Jonathan D.; Gaona, Charles M.; Hogan, R. Edward; Burton, Harold; Corbetta, Maurizio; Leuthardt, Eric C.

    2013-01-01

    Recent advances in basic neuroscience research across a wide range of methodologies have contributed significantly to our understanding of human cortical electrophysiology and functional brain imaging. Translation of this research into clinical neurosurgery has opened doors for advanced mapping of functionality that previously was prohibitively difficult, if not impossible. Here we present the case of a unique individual with congenital blindness and medically refractory epilepsy who underwent neurosurgical treatment of her seizures. Pre-operative evaluation presented the challenge of accurately and robustly mapping the cerebral cortex for an individual with a high probability of significant cortical re-organization. Additionally, a blind individual has unique priorities in one’s ability to read Braille by touch and sense the environment primarily by sound than the non-vision impaired person. For these reasons we employed additional measures to map sensory, motor, speech, language, and auditory perception by employing a number of cortical electrophysiologic mapping and functional magnetic resonance imaging methods. Our data show promising results in the application of these adjunctive methods in the pre-operative mapping of otherwise difficult to localize, and highly variable, functional cortical areas. PMID:23914170

  15. Areas activated during naturalistic reading comprehension overlap topological visual, auditory, and somatotomotor maps

    PubMed Central

    2016-01-01

    Abstract Cortical mapping techniques using fMRI have been instrumental in identifying the boundaries of topological (neighbor‐preserving) maps in early sensory areas. The presence of topological maps beyond early sensory areas raises the possibility that they might play a significant role in other cognitive systems, and that topological mapping might help to delineate areas involved in higher cognitive processes. In this study, we combine surface‐based visual, auditory, and somatomotor mapping methods with a naturalistic reading comprehension task in the same group of subjects to provide a qualitative and quantitative assessment of the cortical overlap between sensory‐motor maps in all major sensory modalities, and reading processing regions. Our results suggest that cortical activation during naturalistic reading comprehension overlaps more extensively with topological sensory‐motor maps than has been heretofore appreciated. Reading activation in regions adjacent to occipital lobe and inferior parietal lobe almost completely overlaps visual maps, whereas a significant portion of frontal activation for reading in dorsolateral and ventral prefrontal cortex overlaps both visual and auditory maps. Even classical language regions in superior temporal cortex are partially overlapped by topological visual and auditory maps. By contrast, the main overlap with somatomotor maps is restricted to a small region on the anterior bank of the central sulcus near the border between the face and hand representations of M‐I. Hum Brain Mapp 37:2784–2810, 2016. © 2016 The Authors Human Brain Mapping Published by Wiley Periodicals, Inc. PMID:27061771

  16. Building the Ferretome

    PubMed Central

    Sukhinin, Dmitrii I.; Engel, Andreas K.; Manger, Paul; Hilgetag, Claus C.

    2016-01-01

    Databases of structural connections of the mammalian brain, such as CoCoMac (cocomac.g-node.org) or BAMS (https://bams1.org), are valuable resources for the analysis of brain connectivity and the modeling of brain dynamics in species such as the non-human primate or the rodent, and have also contributed to the computational modeling of the human brain. Another animal model that is widely used in electrophysiological or developmental studies is the ferret; however, no systematic compilation of brain connectivity is currently available for this species. Thus, we have started developing a database of anatomical connections and architectonic features of the ferret brain, the Ferret(connect)ome, www.Ferretome.org. The Ferretome database has adapted essential features of the CoCoMac methodology and legacy, such as the CoCoMac data model. This data model was simplified and extended in order to accommodate new data modalities that were not represented previously, such as the cytoarchitecture of brain areas. The Ferretome uses a semantic parcellation of brain regions as well as a logical brain map transformation algorithm (objective relational transformation, ORT). The ORT algorithm was also adopted for the transformation of architecture data. The database is being developed in MySQL and has been populated with literature reports on tract-tracing observations in the ferret brain using a custom-designed web interface that allows efficient and validated simultaneous input and proofreading by multiple curators. The database is equipped with a non-specialist web interface. This interface can be extended to produce connectivity matrices in several formats, including a graphical representation superimposed on established ferret brain maps. An important feature of the Ferretome database is the possibility to trace back entries in connectivity matrices to the original studies archived in the system. Currently, the Ferretome contains 50 reports on connections comprising 20 injection reports with more than 150 labeled source and target areas, the majority reflecting connectivity of subcortical nuclei and 15 descriptions of regional brain architecture. We hope that the Ferretome database will become a useful resource for neuroinformatics and neural modeling, and will support studies of the ferret brain as well as facilitate advances in comparative studies of mesoscopic brain connectivity. PMID:27242503

  17. Building the Ferretome.

    PubMed

    Sukhinin, Dmitrii I; Engel, Andreas K; Manger, Paul; Hilgetag, Claus C

    2016-01-01

    Databases of structural connections of the mammalian brain, such as CoCoMac (cocomac.g-node.org) or BAMS (https://bams1.org), are valuable resources for the analysis of brain connectivity and the modeling of brain dynamics in species such as the non-human primate or the rodent, and have also contributed to the computational modeling of the human brain. Another animal model that is widely used in electrophysiological or developmental studies is the ferret; however, no systematic compilation of brain connectivity is currently available for this species. Thus, we have started developing a database of anatomical connections and architectonic features of the ferret brain, the Ferret(connect)ome, www.Ferretome.org. The Ferretome database has adapted essential features of the CoCoMac methodology and legacy, such as the CoCoMac data model. This data model was simplified and extended in order to accommodate new data modalities that were not represented previously, such as the cytoarchitecture of brain areas. The Ferretome uses a semantic parcellation of brain regions as well as a logical brain map transformation algorithm (objective relational transformation, ORT). The ORT algorithm was also adopted for the transformation of architecture data. The database is being developed in MySQL and has been populated with literature reports on tract-tracing observations in the ferret brain using a custom-designed web interface that allows efficient and validated simultaneous input and proofreading by multiple curators. The database is equipped with a non-specialist web interface. This interface can be extended to produce connectivity matrices in several formats, including a graphical representation superimposed on established ferret brain maps. An important feature of the Ferretome database is the possibility to trace back entries in connectivity matrices to the original studies archived in the system. Currently, the Ferretome contains 50 reports on connections comprising 20 injection reports with more than 150 labeled source and target areas, the majority reflecting connectivity of subcortical nuclei and 15 descriptions of regional brain architecture. We hope that the Ferretome database will become a useful resource for neuroinformatics and neural modeling, and will support studies of the ferret brain as well as facilitate advances in comparative studies of mesoscopic brain connectivity.

  18. Brain-machine interfacing control of whole-body humanoid motion

    PubMed Central

    Bouyarmane, Karim; Vaillant, Joris; Sugimoto, Norikazu; Keith, François; Furukawa, Jun-ichiro; Morimoto, Jun

    2014-01-01

    We propose to tackle in this paper the problem of controlling whole-body humanoid robot behavior through non-invasive brain-machine interfacing (BMI), motivated by the perspective of mapping human motor control strategies to human-like mechanical avatar. Our solution is based on the adequate reduction of the controllable dimensionality of a high-DOF humanoid motion in line with the state-of-the-art possibilities of non-invasive BMI technologies, leaving the complement subspace part of the motion to be planned and executed by an autonomous humanoid whole-body motion planning and control framework. The results are shown in full physics-based simulation of a 36-degree-of-freedom humanoid motion controlled by a user through EEG-extracted brain signals generated with motor imagery task. PMID:25140134

  19. High-resolution x-ray absorption spectroscopy studies of metal compounds in neurodegenerative brain tissue

    NASA Astrophysics Data System (ADS)

    Collingwood, J. F.; Mikhaylova, A.; Davidson, M. R.; Batich, C.; Streit, W. J.; Eskin, T.; Terry, J.; Barrea, R.; Underhill, R. S.; Dobson, J.

    2005-01-01

    Fluorescence mapping and microfocus X-ray absorption spectroscopy are used to detect, locate and identify iron biominerals and other inorganic metal accumulations in neurodegenerative brain tissue at sub-cellular resolution (<5 microns). Recent progress in developing the technique is reviewed. Synchrotron X-rays are used to map tissue sections for metals of interest, and XANES and XAFS are used to characterise anomalous concentrations of the metals in-situ so that they can be correlated with tissue structures and disease pathology. Iron anomalies associated with biogenic magnetite, ferritin and haemoglobin are located and identified in an avian tissue model with a pixel resolution ~5 microns. Subsequent studies include brain tissue sections from transgenic Huntington's mice, and the first high-resolution mapping and identification of iron biominerals in human Alzheimer's and control autopsy brain tissue. Technical developments include use of microfocus diffraction to obtain structural information about biominerals in-situ, and depositing sample location grids by lithography for the location of anomalies by conventional microscopy. The combined techniques provide a breakthrough in the study of both intra- and extra-cellular iron compounds and related metals in tissue. The information to be gained from this approach has implications for future diagnosis and treatment of neurodegeneration, and for our understanding of the mechanisms involved.

  20. Fast periodic stimulation (FPS): a highly effective approach in fMRI brain mapping.

    PubMed

    Gao, Xiaoqing; Gentile, Francesco; Rossion, Bruno

    2018-06-01

    Defining the neural basis of perceptual categorization in a rapidly changing natural environment with low-temporal resolution methods such as functional magnetic resonance imaging (fMRI) is challenging. Here, we present a novel fast periodic stimulation (FPS)-fMRI approach to define face-selective brain regions with natural images. Human observers are presented with a dynamic stream of widely variable natural object images alternating at a fast rate (6 images/s). Every 9 s, a short burst of variable face images contrasting with object images in pairs induces an objective face-selective neural response at 0.111 Hz. A model-free Fourier analysis achieves a twofold increase in signal-to-noise ratio compared to a conventional block-design approach with identical stimuli and scanning duration, allowing to derive a comprehensive map of face-selective areas in the ventral occipito-temporal cortex, including the anterior temporal lobe (ATL), in all individual brains. Critically, periodicity of the desired category contrast and random variability among widely diverse images effectively eliminates the contribution of low-level visual cues, and lead to the highest values (80-90%) of test-retest reliability in the spatial activation map yet reported in imaging higher level visual functions. FPS-fMRI opens a new avenue for understanding brain function with low-temporal resolution methods.

  1. 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.

  2. Natural speech reveals the semantic maps that tile human cerebral cortex

    PubMed Central

    Huth, Alexander G.; de Heer, Wendy A.; Griffiths, Thomas L.; Theunissen, Frédéric E.; Gallant, Jack L.

    2016-01-01

    The meaning of language is represented in regions of the cerebral cortex collectively known as the “semantic system”. However, little of the semantic system has been mapped comprehensively, and the semantic selectivity of most regions is unknown. Here we systematically map semantic selectivity across the cortex using voxel-wise modeling of fMRI data collected while subjects listened to hours of narrative stories. We show that the semantic system is organized into intricate patterns that appear consistent across individuals. We then use a novel generative model to create a detailed semantic atlas. Our results suggest that most areas within the semantic system represent information about specific semantic domains, or groups of related concepts, and our atlas shows which domains are represented in each area. This study demonstrates that data-driven methods—commonplace in studies of human neuroanatomy and functional connectivity—provide a powerful and efficient means for mapping functional representations in the brain. PMID:27121839

  3. Sticking with the nice guy: trait warmth information impairs learning and modulates person perception brain network activity.

    PubMed

    Lee, Victoria K; Harris, Lasana T

    2014-12-01

    Social learning requires inferring social information about another person, as well as evaluating outcomes. Previous research shows that prior social information biases decision making and reduces reliance on striatal activity during learning (Delgado, Frank, & Phelps, Nature Neuroscience 8 (11): 1611-1618, 2005). A rich literature in social psychology on person perception demonstrates that people spontaneously infer social information when viewing another person (Fiske & Taylor, 2013) and engage a network of brain regions, including the medial prefrontal cortex, temporal parietal junction, superior temporal sulcus, and precuneus (Amodio & Frith, Nature Reviews Neuroscience, 7(4), 268-277, 2006; Haxby, Gobbini, & Montgomery, 2004; van Overwalle Human Brain Mapping, 30, 829-858, 2009). We investigate the role of these brain regions during social learning about well-established dimensions of person perception-trait warmth and trait competence. We test the hypothesis that activity in person perception brain regions interacts with learning structures during social learning. Participants play an investment game where they must choose an agent to invest on their behalf. This choice is guided by cues signaling trait warmth or trait competence based on framing of monetary returns. Trait warmth information impairs learning about human but not computer agents, while trait competence information produces similar learning rates for human and computer agents. We see increased activation to warmth information about human agents in person perception brain regions. Interestingly, activity in person perception brain regions during the decision phase negatively predicts activity in the striatum during feedback for trait competence inferences about humans. These results suggest that social learning may engage additional processing within person perception brain regions that hampers learning in economic contexts.

  4. Detection of Human Brain Cancer Infiltration ex vivo and in vivo Using Quantitative Optical Coherence Tomography*

    PubMed Central

    Kut, Carmen; Chaichana, Kaisorn L.; Xi, Jiefeng; Raza, Shaan M.; Ye, Xiaobu; McVeigh, Elliot R.; Rodriguez, Fausto J.; Quinones-Hinojosa, Alfredo; Li, Xingde

    2015-01-01

    More complete brain cancer resection can prolong survival and delay recurrence. However, it is challenging to distinguish cancer from non-cancer tissues intraoperatively, especially at the transitional, infiltrative zones. This is especially critical in eloquent regions (e.g. speech and motor areas). This study tested the feasibility of label-free, quantitative optical coherence tomography (OCT) for differentiating cancer from non-cancer in human brain tissues. Fresh ex vivo human brain tissues were obtained from 32 patients with grades II-IV brain cancer and 5 patients with non-cancer brain pathologies. Based on volumetric OCT imaging data, pathologically confirmed brain cancer tissues (both high-grade and low-grade) had significantly lower optical attenuation values at both cancer core and infiltrated zones when compared with non-cancer white matter, and OCT achieved high sensitivity and specificity at an attenuation threshold of 5.5 mm-1 for brain cancer patients. We also used this attenuation threshold to confirm the intraoperative feasibility of performing in vivo OCT-guided surgery using a murine model harboring human brain cancer. Our OCT system was capable of processing and displaying a color-coded optical property map in real time at a rate of 110-215 frames per second, or 1.2-2.4 seconds for an 8-16 mm3 tissue volume, thus providing direct visual cues for cancer versus non-cancer areas. Our study demonstrates the translational and practical potential of OCT in differentiating cancer from non-cancer tissue. Its intraoperative use may facilitate safe and extensive resection of infiltrative brain cancers and consequently lead to improved outcomes when compared with current clinical standards. PMID:26084803

  5. In vivo mapping of brain myo-inositol.

    PubMed

    Haris, Mohammad; Cai, Kejia; Singh, Anup; Hariharan, Hari; Reddy, Ravinder

    2011-02-01

    Myo-Inositol (MI) is one of the most abundant metabolites in the human brain located mainly in glial cells and functions as an osmolyte. The concentration of MI is altered in many brain disorders including Alzheimer's disease and brain tumors. Currently available magnetic resonance spectroscopy (MRS) methods for measuring MI are limited to low spatial resolution. Here, we demonstrate that the hydroxyl protons on MI exhibit chemical exchange with bulk water and saturation of these protons leads to reduction in bulk water signal through a mechanism known as chemical exchange saturation transfer (CEST). The hydroxyl proton exchange rate (k=600 s(-1)) is determined to be in the slow to intermediate exchange regime on the NMR time scale (chemical shift (∆ω)>k), suggesting that the CEST effect of MI (MICEST) can be imaged at high fields such as 7 T (∆ω=1.2×10(3)rad/s) and 9.4 T (∆ω=1.6×10(3) rad/s). Using optimized imaging parameters, concentration dependent broad CEST asymmetry between ~0.2 and 1.5 ppm with a peak at ~0.6 ppm from bulk water was observed. Further, it is demonstrated that MICEST detection is feasible in the human brain at ultra high fields (7 T) without exceeding the allowed limits on radiofrequency specific absorption rate. Results from healthy human volunteers (N=5) showed significantly higher (p=0.03) MICEST effect from white matter (5.2±0.5%) compared to gray matter (4.3±0.5%). The mean coefficient of variations for intra-subject MICEST contrast in WM and GM were 0.49 and 0.58 respectively. Potential overlap of CEST signals from other brain metabolites with the observed MICEST map is discussed. This noninvasive approach potentially opens the way to image MI in vivo and to monitor its alteration in many disease conditions. Copyright © 2010 Elsevier Inc. All rights reserved.

  6. 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

  7. 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.

  8. 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

  9. Evaluation of Atlas-Based Attenuation Correction for Integrated PET/MR in Human Brain: Application of a Head Atlas and Comparison to True CT-Based Attenuation Correction.

    PubMed

    Sekine, Tetsuro; Buck, Alfred; Delso, Gaspar; Ter Voert, Edwin E G W; Huellner, Martin; Veit-Haibach, Patrick; Warnock, Geoffrey

    2016-02-01

    Attenuation correction (AC) for integrated PET/MR imaging in the human brain is still an open problem. In this study, we evaluated a simplified atlas-based AC (Atlas-AC) by comparing (18)F-FDG PET data corrected using either Atlas-AC or true CT data (CT-AC). We enrolled 8 patients (median age, 63 y). All patients underwent clinically indicated whole-body (18)F-FDG PET/CT for staging, restaging, or follow-up of malignant disease. All patients volunteered for an additional PET/MR of the head (additional tracer was not injected). For each patient, 2 AC maps were generated: an Atlas-AC map registered to a patient-specific liver accelerated volume acquisition-Flex MR sequence and using a vendor-provided head atlas generated from multiple CT head images and a CT-based AC map. For comparative AC, the CT-AC map generated from PET/CT was superimposed on the Atlas-AC map. PET images were reconstructed from the list-mode raw data from the PET/MR imaging scanner using each AC map. All PET images were normalized to the SPM5 PET template, and (18)F-FDG accumulation was quantified in 67 volumes of interest (VOIs; automated anatomic labeling atlas). Relative difference (%diff) between images based on Atlas-AC and CT-AC was calculated, and averaged difference images were generated. (18)F-FDG uptake in all VOIs was compared using Bland-Altman analysis. The range of error in all 536 VOIs was -3.0%-7.3%. Whole-brain (18)F-FDG uptake based on Atlas-AC was slightly underestimated (%diff = 2.19% ± 1.40%). The underestimation was most pronounced in the regions below the anterior/posterior commissure line, such as the cerebellum, temporal lobe, and central structures (%diff = 3.69% ± 1.43%, 3.25% ± 1.42%, and 3.05% ± 1.18%), suggesting that Atlas-AC tends to underestimate the attenuation values of the skull base bone. When compared with the gold-standard CT-AC, errors introduced using Atlas-AC did not exceed 8% in any brain region investigated. Underestimation of (18)F-FDG uptake was minor (<4%) but significant in regions near the skull base. © 2016 by the Society of Nuclear Medicine and Molecular Imaging, Inc.

  10. Human Factors and Information Operation for a Nuclear Power Space Vehicle

    NASA Technical Reports Server (NTRS)

    Trujillo, Anna C.; Brown-VanHoozer, S. Alenka

    2002-01-01

    This paper describes human-interactive systems needed for a crewed nuclear-enabled space mission. A synthesis of aircraft engine and nuclear power plant displays, biofeedback of sensory input, virtual control, brain mapping for control process and manipulation, and so forth are becoming viable solutions. These aspects must maintain the crew's situation awareness and performance, which entails a delicate function allocation between crew and automation.

  11. The Expression of DJ-1 (PARK7) in Normal Human CNS and Idiopathic Parkinson's Disease

    ERIC Educational Resources Information Center

    Bandopadhyay, Rina; Kingsbury, Ann E.; Cookson, Mark R.; Reid, Andrew R.; Evans, Ian M.; Hope, Andrew D.; Pittman, Alan M.; Lashley, Tammaryn; Canet-Aviles, Rosa; Miller, David W.; McLendon, Chris; Strand, Catherine; Leonard, Andrew J.; Abou-Sleiman, Patrick M.; Healy, Daniel G.; Ariga, Hiroyashi; Wood, Nicholas W.; de Silva, Rohan; Revesz, Tamas; Hardy, John A.; Lees, Andrew J.

    2004-01-01

    Two mutations in the DJ-1 gene on chromosome1p36 have been identified recently to cause early-onset, autosomal recessive Parkinson's disease. As no information is available regarding the distribution of DJ-1 protein in the human brain, in this study we used a monoclonal antibody for DJ-1 to map its distribution in frontal cortex and substantia…

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

    PubMed Central

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

    2014-01-01

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

  13. Expansion microscopy: development and neuroscience applications.

    PubMed

    Karagiannis, Emmanouil D; Boyden, Edward S

    2018-06-01

    Many neuroscience questions center around understanding how the molecules and wiring in neural circuits mechanistically yield behavioral functions, or go awry in disease states. However, mapping the molecules and wiring of neurons across the large scales of neural circuits has posed a great challenge. We recently developed expansion microscopy (ExM), a process in which we physically magnify biological specimens such as brain circuits. We synthesize throughout preserved brain specimens a dense, even mesh of a swellable polymer such as sodium polyacrylate, anchoring key biomolecules such as proteins and nucleic acids to the polymer. After mechanical homogenization of the specimen-polymer composite, we add water, and the polymer swells, pulling biomolecules apart. Due to the larger separation between molecules, ordinary microscopes can then perform nanoscale resolution imaging. We here review the ExM technology as well as applications to the mapping of synapses, cells, and circuits, including deployment in species such as Drosophila, mouse, non-human primate, and human. Copyright © 2017 Elsevier Ltd. All rights reserved.

  14. Joint genetic analysis of hippocampal size in mouse and human identifies a novel gene linked to neurodegenerative disease.

    PubMed

    Ashbrook, David G; Williams, Robert W; Lu, Lu; Stein, Jason L; Hibar, Derrek P; Nichols, Thomas E; Medland, Sarah E; Thompson, Paul M; Hager, Reinmar

    2014-10-03

    Variation in hippocampal volume has been linked to significant differences in memory, behavior, and cognition among individuals. To identify genetic variants underlying such differences and associated disease phenotypes, multinational consortia such as ENIGMA have used large magnetic resonance imaging (MRI) data sets in human GWAS studies. In addition, mapping studies in mouse model systems have identified genetic variants for brain structure variation with great power. A key challenge is to understand how genetically based differences in brain structure lead to the propensity to develop specific neurological disorders. We combine the largest human GWAS of brain structure with the largest mammalian model system, the BXD recombinant inbred mouse population, to identify novel genetic targets influencing brain structure variation that are linked to increased risk for neurological disorders. We first use a novel cross-species, comparative analysis using mouse and human genetic data to identify a candidate gene, MGST3, associated with adult hippocampus size in both systems. We then establish the coregulation and function of this gene in a comprehensive systems-analysis. We find that MGST3 is associated with hippocampus size and is linked to a group of neurodegenerative disorders, such as Alzheimer's.

  15. NeuroVault.org: A repository for sharing unthresholded statistical maps, parcellations, and atlases of the human brain.

    PubMed

    Gorgolewski, Krzysztof J; Varoquaux, Gael; Rivera, Gabriel; Schwartz, Yannick; Sochat, Vanessa V; Ghosh, Satrajit S; Maumet, Camille; Nichols, Thomas E; Poline, Jean-Baptiste; Yarkoni, Tal; Margulies, Daniel S; Poldrack, Russell A

    2016-01-01

    NeuroVault.org is dedicated to storing outputs of analyses in the form of statistical maps, parcellations and atlases, a unique strategy that contrasts with most neuroimaging repositories that store raw acquisition data or stereotaxic coordinates. Such maps are indispensable for performing meta-analyses, validating novel methodology, and deciding on precise outlines for regions of interest (ROIs). NeuroVault is open to maps derived from both healthy and clinical populations, as well as from various imaging modalities (sMRI, fMRI, EEG, MEG, PET, etc.). The repository uses modern web technologies such as interactive web-based visualization, cognitive decoding, and comparison with other maps to provide researchers with efficient, intuitive tools to improve the understanding of their results. Each dataset and map is assigned a permanent Universal Resource Locator (URL), and all of the data is accessible through a REST Application Programming Interface (API). Additionally, the repository supports the NIDM-Results standard and has the ability to parse outputs from popular FSL and SPM software packages to automatically extract relevant metadata. This ease of use, modern web-integration, and pioneering functionality holds promise to improve the workflow for making inferences about and sharing whole-brain statistical maps. Copyright © 2015 Elsevier Inc. All rights reserved.

  16. Characterizing and Modulating Brain Circuitry through Transcranial Magnetic Stimulation Combined with Electroencephalography.

    PubMed

    Farzan, Faranak; Vernet, Marine; Shafi, Mouhsin M D; Rotenberg, Alexander; Daskalakis, Zafiris J; Pascual-Leone, Alvaro

    2016-01-01

    The concurrent combination of transcranial magnetic stimulation (TMS) with electroencephalography (TMS-EEG) is a powerful technology for characterizing and modulating brain networks across developmental, behavioral, and disease states. Given the global initiatives in mapping the human brain, recognition of the utility of this technique is growing across neuroscience disciplines. Importantly, TMS-EEG offers translational biomarkers that can be applied in health and disease, across the lifespan, and in humans and animals, bridging the gap between animal models and human studies. However, to utilize the full potential of TMS-EEG methodology, standardization of TMS-EEG study protocols is needed. In this article, we review the principles of TMS-EEG methodology, factors impacting TMS-EEG outcome measures, and the techniques for preventing and correcting artifacts in TMS-EEG data. To promote the standardization of this technique, we provide comprehensive guides for designing TMS-EEG studies and conducting TMS-EEG experiments. We conclude by reviewing the application of TMS-EEG in basic, cognitive and clinical neurosciences, and evaluate the potential of this emerging technology in brain research.

  17. Characterizing and Modulating Brain Circuitry through Transcranial Magnetic Stimulation Combined with Electroencephalography

    PubMed Central

    Farzan, Faranak; Vernet, Marine; Shafi, Mouhsin M. D.; Rotenberg, Alexander; Daskalakis, Zafiris J.; Pascual-Leone, Alvaro

    2016-01-01

    The concurrent combination of transcranial magnetic stimulation (TMS) with electroencephalography (TMS-EEG) is a powerful technology for characterizing and modulating brain networks across developmental, behavioral, and disease states. Given the global initiatives in mapping the human brain, recognition of the utility of this technique is growing across neuroscience disciplines. Importantly, TMS-EEG offers translational biomarkers that can be applied in health and disease, across the lifespan, and in humans and animals, bridging the gap between animal models and human studies. However, to utilize the full potential of TMS-EEG methodology, standardization of TMS-EEG study protocols is needed. In this article, we review the principles of TMS-EEG methodology, factors impacting TMS-EEG outcome measures, and the techniques for preventing and correcting artifacts in TMS-EEG data. To promote the standardization of this technique, we provide comprehensive guides for designing TMS-EEG studies and conducting TMS-EEG experiments. We conclude by reviewing the application of TMS-EEG in basic, cognitive and clinical neurosciences, and evaluate the potential of this emerging technology in brain research. PMID:27713691

  18. Chemical exchange saturation transfer MRI contrast in the human brain at 9.4 T.

    PubMed

    Zaiss, Moritz; Schuppert, Mark; Deshmane, Anagha; Herz, Kai; Ehses, Philipp; Füllbier, Lars; Lindig, Tobias; Bender, Benjamin; Ernemann, Ulrike; Scheffler, Klaus

    2018-06-15

    The high chemical shift separation at 9.4 T allows for selective saturation of proton pools in exchange with water protons. For the first time, highly selective and comprehensive chemical exchange saturation transfer (CEST) experiments were performed in the human brain at 9.4 T. This work provides insight into CEST signals in the human brain in comparison with existing animal studies, as well as with CEST effects in vivo at lower field strengths. A novel snapshot-CEST method for human brain scans at 9.4 T was optimized and employed for highly-spectrally-resolved (95 offsets) CEST measurements in healthy subjects and one brain tumor patient. Reproducibility and stability between scans was verified in grey and white matter after B 0 , B 1 , and motion correction of the acquired 3D CEST volumes. Two-step Lorentzian fitting was used to further improve separation of spectrally discernible signals to create known and novel CEST contrast maps at 9.4 T. At a saturation power of B 1  = 0.5 μT most selective CEST effects could be obtained in the human brain with high inter-scan reproducibility. While contrast behavior of previously measured signals at lower field, namely amide-, guanidyl- and NOE-CEST effects, could be reproduced, novel signals at 2.7 ppm, and -1.6 ppm could be verified in healthy subjects and in a brain tumor patient for the first time. High spectral resolution chemical exchange saturation transfer at 9.4 T allows deeper insights into the Z-spectrum structure of the human brain, and provides many different contrasts showing different correlations in healthy tissue and in tumor-affected areas of the brain, generating hypotheses for future investigations of in-vivo-CEST at UHF. Copyright © 2018 Elsevier Inc. All rights reserved.

  19. Minimum spanning tree analysis of the human connectome.

    PubMed

    van Dellen, Edwin; Sommer, Iris E; Bohlken, Marc M; Tewarie, Prejaas; Draaisma, Laurijn; Zalesky, Andrew; Di Biase, Maria; Brown, Jesse A; Douw, Linda; Otte, Willem M; Mandl, René C W; Stam, Cornelis J

    2018-06-01

    One of the challenges of brain network analysis is to directly compare network organization between subjects, irrespective of the number or strength of connections. In this study, we used minimum spanning tree (MST; a unique, acyclic subnetwork with a fixed number of connections) analysis to characterize the human brain network to create an empirical reference network. Such a reference network could be used as a null model of connections that form the backbone structure of the human brain. We analyzed the MST in three diffusion-weighted imaging datasets of healthy adults. The MST of the group mean connectivity matrix was used as the empirical null-model. The MST of individual subjects matched this reference MST for a mean 58%-88% of connections, depending on the analysis pipeline. Hub nodes in the MST matched with previously reported locations of hub regions, including the so-called rich club nodes (a subset of high-degree, highly interconnected nodes). Although most brain network studies have focused primarily on cortical connections, cortical-subcortical connections were consistently present in the MST across subjects. Brain network efficiency was higher when these connections were included in the analysis, suggesting that these tracts may be utilized as the major neural communication routes. Finally, we confirmed that MST characteristics index the effects of brain aging. We conclude that the MST provides an elegant and straightforward approach to analyze structural brain networks, and to test network topological features of individual subjects in comparison to empirical null models. © 2018 The Authors Human Brain Mapping Published by Wiley Periodicals, Inc.

  20. Reference frames in virtual spatial navigation are viewpoint dependent

    PubMed Central

    Török, Ágoston; Nguyen, T. Peter; Kolozsvári, Orsolya; Buchanan, Robert J.; Nadasdy, Zoltan

    2014-01-01

    Spatial navigation in the mammalian brain relies on a cognitive map of the environment. Such cognitive maps enable us, for example, to take the optimal route from a given location to a known target. The formation of these maps is naturally influenced by our perception of the environment, meaning it is dependent on factors such as our viewpoint and choice of reference frame. Yet, it is unknown how these factors influence the construction of cognitive maps. Here, we evaluated how various combinations of viewpoints and reference frames affect subjects' performance when they navigated in a bounded virtual environment without landmarks. We measured both their path length and time efficiency and found that (1) ground perspective was associated with egocentric frame of reference, (2) aerial perspective was associated with allocentric frame of reference, (3) there was no appreciable performance difference between first and third person egocentric viewing positions and (4) while none of these effects were dependent on gender, males tended to perform better in general. Our study provides evidence that there are inherent associations between visual perspectives and cognitive reference frames. This result has implications about the mechanisms of path integration in the human brain and may also inspire designs of virtual reality applications. Lastly, we demonstrated the effective use of a tablet PC and spatial navigation tasks for studying spatial and cognitive aspects of human memory. PMID:25249956

  1. Reference frames in virtual spatial navigation are viewpoint dependent.

    PubMed

    Török, Agoston; Nguyen, T Peter; Kolozsvári, Orsolya; Buchanan, Robert J; Nadasdy, Zoltan

    2014-01-01

    Spatial navigation in the mammalian brain relies on a cognitive map of the environment. Such cognitive maps enable us, for example, to take the optimal route from a given location to a known target. The formation of these maps is naturally influenced by our perception of the environment, meaning it is dependent on factors such as our viewpoint and choice of reference frame. Yet, it is unknown how these factors influence the construction of cognitive maps. Here, we evaluated how various combinations of viewpoints and reference frames affect subjects' performance when they navigated in a bounded virtual environment without landmarks. We measured both their path length and time efficiency and found that (1) ground perspective was associated with egocentric frame of reference, (2) aerial perspective was associated with allocentric frame of reference, (3) there was no appreciable performance difference between first and third person egocentric viewing positions and (4) while none of these effects were dependent on gender, males tended to perform better in general. Our study provides evidence that there are inherent associations between visual perspectives and cognitive reference frames. This result has implications about the mechanisms of path integration in the human brain and may also inspire designs of virtual reality applications. Lastly, we demonstrated the effective use of a tablet PC and spatial navigation tasks for studying spatial and cognitive aspects of human memory.

  2. Top-down predictions in the cognitive brain

    PubMed Central

    Kveraga, Kestutis; Ghuman, Avniel S.; Bar, Moshe

    2007-01-01

    The human brain is not a passive organ simply waiting to be activated by external stimuli. Instead, it is proposed tat the brain continuously employs memory of past experiences to interpret sensory information and predict the immediately relevant future. This review concentrates on visual recognition as the model system for developing and testing ideas about the role and mechanisms of top-down predictions in the brain. We cover relevant behavioral, computational and neural aspects. These ideas are then extended to other domains. The basic elements of this proposal include analogical mapping, associative representations and the generation of predictions. Connections to a host of cognitive processes will be made and implications to several mental disorders will be proposed. PMID:17923222

  3. Salt-Induced Hypertension in a Mouse Model of Liddle's Syndrome is Mediated by Epithelial Sodium Channels in the Brain

    PubMed Central

    Van Huysse, James W.; Amin, Md. Shahrier; Yang, Baoli; Leenen, Frans H. H.

    2012-01-01

    Neural precursor cell expressed and developmentally downregulated 4-2 protein (Nedd4-2) facilitates the endocytosis of epithelial Na channels (ENaC). Both mice and humans with a loss of regulation of ENaC by Nedd4-2 have salt-induced hypertension. ENaC is also expressed in the brain, where it is critical for hypertension on high salt diet in salt-sensitive rats. In the present studies we assessed whether Nedd4-2 knockout (−/−) mice have: 1) increased brain ENaC; 2) elevated CSF sodium on high salt diet; and 3) enhanced pressor responses to CSF sodium and hypertension on high salt diet, both mediated by brain ENaC. Prominent choroid plexus and neuronal ENaC staining was present in −/− but not in wild-type (W/T) mice. In chronically instrumented mice, intracerebroventricular (icv) infusion of Na-rich aCSF increased MAP 3-fold higher in −/− than W/T. Icv infusion of the ENaC blocker benzamil abolished this enhancement. In telemetered −/− mice on high salt diet (8% NaCl), CSF [Na+], MAP and HR increased significantly, MAP by 30-35 mmHg. These MAP and HR responses were largely prevented by icv benzamil, but only to a minor extent by sc benzamil at the icv rate. We conclude that increased ENaC expression in the brain of Nedd 4-2 −/− mice mediates their hypertensive response to high salt diet, by causing increased sodium levels in the CSF as well as hyper-responsiveness to CSF sodium. These findings highlight the possible causative contribution of CNS ENaC in the etiology of salt-induced hypertension. PMID:22802227

  4. Brain temperature in volunteers subjected to intranasal cooling.

    PubMed

    Covaciu, L; Weis, J; Bengtsson, C; Allers, M; Lunderquist, A; Ahlström, H; Rubertsson, S

    2011-08-01

    Intranasal cooling can be used to initiate therapeutic hypothermia. However, direct measurement of brain temperature is difficult and the intra-cerebral distribution of temperature changes with cooling is unknown. The purpose of this study was to measure the brain temperature of human volunteers subjected to intranasal cooling using non-invasive magnetic resonance (MR) methods. Intranasal balloons catheters circulated with saline at 20°C were applied for 60 min in ten awake volunteers. No sedation was used. Brain temperature changes were measured and mapped using MR spectroscopic imaging (MRSI) and phase-mapping techniques. Heart rate and blood pressure were monitored throughout the experiment. Rectal temperature was measured before and after the cooling. Mini Mental State Examination (MMSE) test and nasal inspection were done before and after the cooling. Questionnaires about the subjects' personal experience were completed after the experiment. Brain temperature decrease measured by MRSI was -1.7 ± 0.8°C and by phase-mapping -1.8 ± 0.9°C (n = 9) at the end of cooling. Spatial distribution of temperature changes was relatively uniform. Rectal temperature decreased by -0.5 ± 0.3°C (n = 5). The physiological parameters were stable and no shivering was reported. The volunteers remained alert during cooling and no cognitive dysfunctions were apparent in the MMSE test. Postcooling nasal examination detected increased nasal secretion in nine of the ten volunteers. Volunteers' acceptance of the method was good. Both MR techniques revealed brain temperature reductions after 60 min of intranasal cooling with balloons circulated with saline at 20°C in awake, unsedated volunteers.

  5. Reading in the brain of children and adults: A meta‐analysis of 40 functional magnetic resonance imaging studies

    PubMed Central

    Martin, Anna; Schurz, Matthias; Kronbichler, Martin

    2015-01-01

    Abstract We used quantitative, coordinate‐based meta‐analysis to objectively synthesize age‐related commonalities and differences in brain activation patterns reported in 40 functional magnetic resonance imaging (fMRI) studies of reading in children and adults. Twenty fMRI studies with adults (age means: 23–34 years) were matched to 20 studies with children (age means: 7–12 years). The separate meta‐analyses of these two sets showed a pattern of reading‐related brain activation common to children and adults in left ventral occipito‐temporal (OT), inferior frontal, and posterior parietal regions. The direct statistical comparison between the two meta‐analytic maps of children and adults revealed higher convergence in studies with children in left superior temporal and bilateral supplementary motor regions. In contrast, higher convergence in studies with adults was identified in bilateral posterior OT/cerebellar and left dorsal precentral regions. The results are discussed in relation to current neuroanatomical models of reading and tentative functional interpretations of reading‐related activation clusters in children and adults are provided. Hum Brain Mapp 36:1963–1981, 2015. © 2015 The Authors Human Brain Mapping Published by Wiley Periodicals, Inc.. PMID:25628041

  6. Robust and fast characterization of OCT-based optical attenuation using a novel frequency-domain algorithm for brain cancer detection

    NASA Astrophysics Data System (ADS)

    Yuan, Wu; Kut, Carmen; Liang, Wenxuan; Li, Xingde

    2017-03-01

    Cancer is known to alter the local optical properties of tissues. The detection of OCT-based optical attenuation provides a quantitative method to efficiently differentiate cancer from non-cancer tissues. In particular, the intraoperative use of quantitative OCT is able to provide a direct visual guidance in real time for accurate identification of cancer tissues, especially these without any obvious structural layers, such as brain cancer. However, current methods are suboptimal in providing high-speed and accurate OCT attenuation mapping for intraoperative brain cancer detection. In this paper, we report a novel frequency-domain (FD) algorithm to enable robust and fast characterization of optical attenuation as derived from OCT intensity images. The performance of this FD algorithm was compared with traditional fitting methods by analyzing datasets containing images from freshly resected human brain cancer and from a silica phantom acquired by a 1310 nm swept-source OCT (SS-OCT) system. With graphics processing unit (GPU)-based CUDA C/C++ implementation, this new attenuation mapping algorithm can offer robust and accurate quantitative interpretation of OCT images in real time during brain surgery.

  7. 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.

  8. Uses, misuses, new uses and fundamental limitations of magnetic resonance imaging in cognitive science

    PubMed Central

    2016-01-01

    When blood oxygenation level-dependent (BOLD) contrast functional magnetic resonance imaging (fMRI) was discovered in the early 1990s, it provoked an explosion of interest in exploring human cognition, using brain mapping techniques based on MRI. Standards for data acquisition and analysis were rapidly put in place, in order to assist comparison of results across laboratories. Recently, MRI data acquisition capabilities have improved dramatically, inviting a rethink of strategies for relating functional brain activity at the systems level with its neuronal substrates and functional connections. This paper reviews the established capabilities of BOLD contrast fMRI, the perceived weaknesses of major methods of analysis, and current results that may provide insights into improved brain modelling. These results have inspired the use of in vivo myeloarchitecture for localizing brain activity, individual subject analysis without spatial smoothing and mapping of changes in cerebral blood volume instead of BOLD activation changes. The apparent fundamental limitations of all methods based on nuclear magnetic resonance are also discussed. This article is part of the themed issue ‘Interpreting BOLD: a dialogue between cognitive and cellular neuroscience’. PMID:27574303

  9. Uses, misuses, new uses and fundamental limitations of magnetic resonance imaging in cognitive science.

    PubMed

    Turner, Robert

    2016-10-05

    When blood oxygenation level-dependent (BOLD) contrast functional magnetic resonance imaging (fMRI) was discovered in the early 1990s, it provoked an explosion of interest in exploring human cognition, using brain mapping techniques based on MRI. Standards for data acquisition and analysis were rapidly put in place, in order to assist comparison of results across laboratories. Recently, MRI data acquisition capabilities have improved dramatically, inviting a rethink of strategies for relating functional brain activity at the systems level with its neuronal substrates and functional connections. This paper reviews the established capabilities of BOLD contrast fMRI, the perceived weaknesses of major methods of analysis, and current results that may provide insights into improved brain modelling. These results have inspired the use of in vivo myeloarchitecture for localizing brain activity, individual subject analysis without spatial smoothing and mapping of changes in cerebral blood volume instead of BOLD activation changes. The apparent fundamental limitations of all methods based on nuclear magnetic resonance are also discussed.This article is part of the themed issue 'Interpreting BOLD: a dialogue between cognitive and cellular neuroscience'. © 2016 The Authors.

  10. Brain maps 4.0-Structure of the rat brain: An open access atlas with global nervous system nomenclature ontology and flatmaps.

    PubMed

    Swanson, Larry W

    2018-04-15

    The fourth edition (following editions in 1992, 1998, 2004) of Brain maps: structure of the rat brain is presented here as an open access internet resource for the neuroscience community. One new feature is a set of 10 hierarchical nomenclature tables that define and describe all parts of the rat nervous system within the framework of a strictly topographic system devised previously for the human nervous system. These tables constitute a global ontology for knowledge management systems dealing with neural circuitry. A second new feature is an aligned atlas of bilateral flatmaps illustrating rat nervous system development from the neural plate stage to the adult stage, where most gray matter regions, white matter tracts, ganglia, and nerves listed in the nomenclature tables are illustrated schematically. These flatmaps are convenient for future development of online applications analogous to "Google Maps" for systems neuroscience. The third new feature is a completely revised Atlas of the rat brain in spatially aligned transverse sections that can serve as a framework for 3-D modeling. Atlas parcellation is little changed from the preceding edition, but the nomenclature for rat is now aligned with an emerging panmammalian neuroanatomical nomenclature. All figures are presented in Adobe Illustrator vector graphics format that can be manipulated, modified, and resized as desired, and freely used with a Creative Commons license. © 2018 The Authors The Journal of Comparative Neurology Published by Wiley Periodicals, Inc.

  11. Being First Matters: Topographical Representational Similarity Analysis of ERP Signals Reveals Separate Networks for Audiovisual Temporal Binding Depending on the Leading Sense.

    PubMed

    Cecere, Roberto; Gross, Joachim; Willis, Ashleigh; Thut, Gregor

    2017-05-24

    In multisensory integration, processing in one sensory modality is enhanced by complementary information from other modalities. Intersensory timing is crucial in this process because only inputs reaching the brain within a restricted temporal window are perceptually bound. Previous research in the audiovisual field has investigated various features of the temporal binding window, revealing asymmetries in its size and plasticity depending on the leading input: auditory-visual (AV) or visual-auditory (VA). Here, we tested whether separate neuronal mechanisms underlie this AV-VA dichotomy in humans. We recorded high-density EEG while participants performed an audiovisual simultaneity judgment task including various AV-VA asynchronies and unisensory control conditions (visual-only, auditory-only) and tested whether AV and VA processing generate different patterns of brain activity. After isolating the multisensory components of AV-VA event-related potentials (ERPs) from the sum of their unisensory constituents, we ran a time-resolved topographical representational similarity analysis (tRSA) comparing the AV and VA ERP maps. Spatial cross-correlation matrices were built from real data to index the similarity between the AV and VA maps at each time point (500 ms window after stimulus) and then correlated with two alternative similarity model matrices: AV maps = VA maps versus AV maps ≠ VA maps The tRSA results favored the AV maps ≠ VA maps model across all time points, suggesting that audiovisual temporal binding (indexed by synchrony perception) engages different neural pathways depending on the leading sense. The existence of such dual route supports recent theoretical accounts proposing that multiple binding mechanisms are implemented in the brain to accommodate different information parsing strategies in auditory and visual sensory systems. SIGNIFICANCE STATEMENT Intersensory timing is a crucial aspect of multisensory integration, determining whether and how inputs in one modality enhance stimulus processing in another modality. Our research demonstrates that evaluating synchrony of auditory-leading (AV) versus visual-leading (VA) audiovisual stimulus pairs is characterized by two distinct patterns of brain activity. This suggests that audiovisual integration is not a unitary process and that different binding mechanisms are recruited in the brain based on the leading sense. These mechanisms may be relevant for supporting different classes of multisensory operations, for example, auditory enhancement of visual attention (AV) and visual enhancement of auditory speech (VA). Copyright © 2017 Cecere et al.

  12. Revealing pathologies in the liquid crystalline structures of the brain by polarimetric studies (Presentation Recording)

    NASA Astrophysics Data System (ADS)

    Bakhshetyan, Karen; Melkonyan, Gurgen G.; Galstian, Tigran V.; Saghatelyan, Armen

    2015-10-01

    Natural or "self" alignment of molecular complexes in living tissue represents many similarities with liquid crystals (LC), which are anisotropic liquids. The orientational characteristics of those complexes may be related to many important functional parameters and their study may reveal important pathologies. The know-how, accumulated thanks to the study of LC materials, may thus be used to this end. One of the traditionally used methods, to characterize those materials, is the polarized light imaging (PLI) that allows for label-free analysis of anisotropic structures in the brain tissue and can be used, for example, for the analysis of myelinated fiber bundles. In the current work, we first attempted to apply the PLI on the mouse histological brain sections to create a map of anisotropic structures using cross-polarizer transmission light. Then we implemented the PLI for comparative study of histological sections of human postmortem brain samples under normal and pathological conditions, such as Parkinson's disease (PD). Imaging the coronal, sagittal and horizontal sections of mouse brain allowed us to create a false color-coded fiber orientation map under polarized light. In human brain datasets for both control and PD groups we measured the pixel intensities in myelin-rich subregions of internal capsule and normalized these to non-myelinated background signal from putamen and caudate nucleus. Quantification of intensities revealed a statistically significant reduction of fiber intensity of PD compared to control subjects (2.801 +/- 0.303 and 3.724 +/- 0.07 respectively; *p < 0.05). Our study confirms the validity of PLI method for visualizing myelinated axonal fibers. This relatively simple technique can become a promising tool for study of neurodegenerative diseases where labeling-free imaging is an important benefit.

  13. Mapping neurotransmitter networks with PET: an example on serotonin and opioid systems.

    PubMed

    Tuominen, Lauri; Nummenmaa, Lauri; Keltikangas-Järvinen, Liisa; Raitakari, Olli; Hietala, Jarmo

    2014-05-01

    All functions of the human brain are consequences of altered activity of specific neural pathways and neurotransmitter systems. Although the knowledge of "system level" connectivity in the brain is increasing rapidly, we lack "molecular level" information on brain networks and connectivity patterns. We introduce novel voxel-based positron emission tomography (PET) methods for studying internal neurotransmitter network structure and intercorrelations of different neurotransmitter systems in the human brain. We chose serotonin transporter and μ-opioid receptor for this analysis because of their functional interaction at the cellular level and similar regional distribution in the brain. Twenty-one healthy subjects underwent two consecutive PET scans using [(11)C]MADAM, a serotonin transporter tracer, and [(11)C]carfentanil, a μ-opioid receptor tracer. First, voxel-by-voxel "intracorrelations" (hub and seed analyses) were used to study the internal structure of opioid and serotonin systems. Second, voxel-level opioid-serotonin intercorrelations (between neurotransmitters) were computed. Regional μ-opioid receptor binding potentials were uniformly correlated throughout the brain. However, our analyses revealed nonuniformity in the serotonin transporter intracorrelations and identified a highly connected local network (midbrain-striatum-thalamus-amygdala). Regionally specific intercorrelations between the opioid and serotonin tracers were found in anteromedial thalamus, amygdala, anterior cingulate cortex, dorsolateral prefrontal cortex, and left parietal cortex, i.e., in areas relevant for several neuropsychiatric disorders, especially affective disorders. This methodology enables in vivo mapping of connectivity patterns within and between neurotransmitter systems. Quantification of functional neurotransmitter balances may be a useful approach in etiological studies of neuropsychiatric disorders and also in drug development as a biomarker-based rationale for targeted modulation of neurotransmitter networks. Copyright © 2013 Wiley Periodicals, Inc.

  14. 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.

  15. White Matter Fiber-based Analysis of T1w/T2w Ratio Map.

    PubMed

    Chen, Haiwei; Budin, Francois; Noel, Jean; Prieto, Juan Carlos; Gilmore, John; Rasmussen, Jerod; Wadhwa, Pathik D; Entringer, Sonja; Buss, Claudia; Styner, Martin

    2017-02-01

    To develop, test, evaluate and apply a novel tool for the white matter fiber-based analysis of T1w/T2w ratio maps quantifying myelin content. The cerebral white matter in the human brain develops from a mostly non-myelinated state to a nearly fully mature white matter myelination within the first few years of life. High resolution T1w/T2w ratio maps are believed to be effective in quantitatively estimating myelin content on a voxel-wise basis. We propose the use of a fiber-tract-based analysis of such T1w/T2w ratio data, as it allows us to separate fiber bundles that a common regional analysis imprecisely groups together, and to associate effects to specific tracts rather than large, broad regions. We developed an intuitive, open source tool to facilitate such fiber-based studies of T1w/T2w ratio maps. Via its Graphical User Interface (GUI) the tool is accessible to non-technical users. The framework uses calibrated T1w/T2w ratio maps and a prior fiber atlas as an input to generate profiles of T1w/T2w values. The resulting fiber profiles are used in a statistical analysis that performs along-tract functional statistical analysis. We applied this approach to a preliminary study of early brain development in neonates. We developed an open-source tool for the fiber based analysis of T1w/T2w ratio maps and tested it in a study of brain development.

  16. Wide-area mapping of resting state hemodynamic correlations at microvascular resolution with multi-contrast optical imaging (Conference Presentation)

    NASA Astrophysics Data System (ADS)

    Senarathna, Janaka; Hadjiabadi, Darian; Gil, Stacy; Thakor, Nitish V.; Pathak, Arvind P.

    2017-02-01

    Different brain regions exhibit complex information processing even at rest. Therefore, assessing temporal correlations between regions permits task-free visualization of their `resting state connectivity'. Although functional MRI (fMRI) is widely used for mapping resting state connectivity in the human brain, it is not well suited for `microvascular scale' imaging in rodents because of its limited spatial resolution. Moreover, co-registered cerebral blood flow (CBF) and total hemoglobin (HbT) data are often unavailable in conventional fMRI experiments. Therefore, we built a customized system that combines laser speckle contrast imaging (LSCI), intrinsic optical signal (IOS) imaging and fluorescence imaging (FI) to generate multi-contrast functional connectivity maps at a spatial resolution of 10 μm. This system comprised of three illumination sources: a 632 nm HeNe laser (for LSCI), a 570 nm ± 5 nm filtered white light source (for IOS), and a 473 nm blue laser (for FI), as well as a sensitive CCD camera operating at 10 frames per second for image acquisition. The acquired data enabled visualization of changes in resting state neurophysiology at microvascular spatial scales. Moreover, concurrent mapping of CBF and HbT-based temporal correlations enabled in vivo mapping of how resting brain regions were linked in terms of their hemodynamics. Additionally, we complemented this approach by exploiting the transit times of a fluorescent tracer (Dextran-FITC) to distinguish arterial from venous perfusion. Overall, we demonstrated the feasibility of wide area mapping of resting state connectivity at microvascular resolution and created a new toolbox for interrogating neurovascular function.

  17. White matter fiber-based analysis of T1w/T2w ratio map

    NASA Astrophysics Data System (ADS)

    Chen, Haiwei; Budin, Francois; Noel, Jean; Prieto, Juan Carlos; Gilmore, John; Rasmussen, Jerod; Wadhwa, Pathik D.; Entringer, Sonja; Buss, Claudia; Styner, Martin

    2017-02-01

    Purpose: To develop, test, evaluate and apply a novel tool for the white matter fiber-based analysis of T1w/T2w ratio maps quantifying myelin content. Background: The cerebral white matter in the human brain develops from a mostly non-myelinated state to a nearly fully mature white matter myelination within the first few years of life. High resolution T1w/T2w ratio maps are believed to be effective in quantitatively estimating myelin content on a voxel-wise basis. We propose the use of a fiber-tract-based analysis of such T1w/T2w ratio data, as it allows us to separate fiber bundles that a common regional analysis imprecisely groups together, and to associate effects to specific tracts rather than large, broad regions. Methods: We developed an intuitive, open source tool to facilitate such fiber-based studies of T1w/T2w ratio maps. Via its Graphical User Interface (GUI) the tool is accessible to non-technical users. The framework uses calibrated T1w/T2w ratio maps and a prior fiber atlas as an input to generate profiles of T1w/T2w values. The resulting fiber profiles are used in a statistical analysis that performs along-tract functional statistical analysis. We applied this approach to a preliminary study of early brain development in neonates. Results: We developed an open-source tool for the fiber based analysis of T1w/T2w ratio maps and tested it in a study of brain development.

  18. Women's clitoris, vagina and cervix mapped on the sensory cortex: fMRI evidence

    PubMed Central

    Komisaruk, Barry R.; Wise, Nan; Frangos, Eleni; Liu, Wen-Ching; Allen, Kachina; Brody, Stuart

    2011-01-01

    Introduction The projection of vagina, uterine cervix, and nipple to the sensory cortex in humans has not been reported. Aims To map the sensory cortical fields of the clitoris, vagina, cervix and nipple, toward an elucidation of the neural systems underlying sexual response. Methods Using functional Magnetic Resonance Imaging (fMRI) we mapped sensory cortical responses to clitoral, vaginal, cervical, and nipple self-stimulation. For points of reference on the homunculus, we also mapped responses to the thumb and great toe (hallux) stimulation. Main Outcome Measures fMRI of brain regions activated by the various sensory stimuli. Results Clitoral, vaginal, and cervical self-stimulation activate differentiable sensory cortical regions, all clustered in the medial cortex (medial paracentral lobule). Nipple self-stimulation activated the genital sensory cortex (as well as the thoracic) region of the homuncular map. Conclusion The genital sensory cortex, identified in the classical Penfield homunculus based on electrical stimulation of the brain only in men, was confirmed for the first time in the literature by the present study in women, applying clitoral, vaginal, and cervical self-stimulation, and observing their regional brain responses using fMRI. Vaginal, clitoral, and cervical regions of activation were differentiable, consistent with innervation by different afferent nerves and different behavioral correlates. Activation of the genital sensory cortex by nipple self-stimulation was unexpected, but suggests a neurological basis for women’s reports of its erotogenic quality. PMID:21797981

  19. 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.

  20. Study of the development of fetal baboon brain using magnetic resonance imaging at 3 Tesla

    PubMed Central

    Liu, Feng; Garland, Marianne; Duan, Yunsuo; Stark, Raymond I.; Xu, Dongrong; Dong, Zhengchao; Bansal, Ravi; Peterson, Bradley S.; Kangarlu, Alayar

    2008-01-01

    Direct observational data on the development of the brains of human and nonhuman primates is on remarkably scant, and most of our understanding of primate brain development is extrapolated from findings in rodent models. Magnetic resonance imaging (MRI) is a promising tool for the noninvasive, longitudinal study of the developing primate brain. We devised a protocol to scan pregnant baboons serially at 3 T for up to 3 h per session. Seven baboons were scanned 1–6 times, beginning as early as 56 days post-conceptional age, and as late as 185 days (term ~185 days). Successful scanning of the fetal baboon required careful animal preparation and anesthesia, in addition to optimization of the scanning protocol. We successfully acquired maps of relaxation times (T1 and T2) and high-resolution anatomical images of the brains of fetal baboons at multiple time points during the course of gestation. These images demonstrated the convergence of gray and white matter contrast near term, and furthermore demonstrated that the loss of contrast at that age is a consequence of the continuous change in relaxation times during fetal brain development. These data furthermore demonstrate that maps of relaxation times have clear advantages over the relaxation time weighted images for the tracking of the changes in brain structure during fetal development. This protocol for in utero MRI of fetal baboon brains will help to advance the use of nonhuman primate models to study fetal brain development longitudinally. PMID:18155925

  1. Whole-brain activity mapping onto a zebrafish brain atlas.

    PubMed

    Randlett, Owen; Wee, Caroline L; Naumann, Eva A; Nnaemeka, Onyeka; Schoppik, David; Fitzgerald, James E; Portugues, Ruben; Lacoste, Alix M B; Riegler, Clemens; Engert, Florian; Schier, Alexander F

    2015-11-01

    In order to localize the neural circuits involved in generating behaviors, it is necessary to assign activity onto anatomical maps of the nervous system. Using brain registration across hundreds of larval zebrafish, we have built an expandable open-source atlas containing molecular labels and definitions of anatomical regions, the Z-Brain. Using this platform and immunohistochemical detection of phosphorylated extracellular signal–regulated kinase (ERK) as a readout of neural activity, we have developed a system to create and contextualize whole-brain maps of stimulus- and behavior-dependent neural activity. This mitogen-activated protein kinase (MAP)-mapping assay is technically simple, and data analysis is completely automated. Because MAP-mapping is performed on freely swimming fish, it is applicable to studies of nearly any stimulus or behavior. Here we demonstrate our high-throughput approach using pharmacological, visual and noxious stimuli, as well as hunting and feeding. The resultant maps outline hundreds of areas associated with behaviors.

  2. Mapping of Human FOXP2 Enhancers Reveals Complex Regulation.

    PubMed

    Becker, Martin; Devanna, Paolo; Fisher, Simon E; Vernes, Sonja C

    2018-01-01

    Mutations of the FOXP2 gene cause a severe speech and language disorder, providing a molecular window into the neurobiology of language. Individuals with FOXP2 mutations have structural and functional alterations affecting brain circuits that overlap with sites of FOXP2 expression, including regions of the cortex, striatum, and cerebellum. FOXP2 displays complex patterns of expression in the brain, as well as in non-neuronal tissues, suggesting that sophisticated regulatory mechanisms control its spatio-temporal expression. However, to date, little is known about the regulation of FOXP2 or the genomic elements that control its expression. Using chromatin conformation capture (3C), we mapped the human FOXP2 locus to identify putative enhancer regions that engage in long-range interactions with the promoter of this gene. We demonstrate the ability of the identified enhancer regions to drive gene expression. We also show regulation of the FOXP2 promoter and enhancer regions by candidate regulators - FOXP family and TBR1 transcription factors. These data point to regulatory elements that may contribute to the temporal- or tissue-specific expression patterns of human FOXP2 . Understanding the upstream regulatory pathways controlling FOXP2 expression will bring new insight into the molecular networks contributing to human language and related disorders.

  3. Mapping of Human FOXP2 Enhancers Reveals Complex Regulation

    PubMed Central

    Becker, Martin; Devanna, Paolo; Fisher, Simon E.; Vernes, Sonja C.

    2018-01-01

    Mutations of the FOXP2 gene cause a severe speech and language disorder, providing a molecular window into the neurobiology of language. Individuals with FOXP2 mutations have structural and functional alterations affecting brain circuits that overlap with sites of FOXP2 expression, including regions of the cortex, striatum, and cerebellum. FOXP2 displays complex patterns of expression in the brain, as well as in non-neuronal tissues, suggesting that sophisticated regulatory mechanisms control its spatio-temporal expression. However, to date, little is known about the regulation of FOXP2 or the genomic elements that control its expression. Using chromatin conformation capture (3C), we mapped the human FOXP2 locus to identify putative enhancer regions that engage in long-range interactions with the promoter of this gene. We demonstrate the ability of the identified enhancer regions to drive gene expression. We also show regulation of the FOXP2 promoter and enhancer regions by candidate regulators – FOXP family and TBR1 transcription factors. These data point to regulatory elements that may contribute to the temporal- or tissue-specific expression patterns of human FOXP2. Understanding the upstream regulatory pathways controlling FOXP2 expression will bring new insight into the molecular networks contributing to human language and related disorders. PMID:29515369

  4. From Complex B1 Mapping to Local SAR Estimation for Human Brain MR Imaging Using Multi-channel Transceiver Coil at 7T

    PubMed Central

    Zhang, Xiaotong; Schmitter, Sebastian; Van de Moortel, Pierre-François; Liu, Jiaen

    2014-01-01

    Elevated Specific Absorption Rate (SAR) associated with increased main magnetic field strength remains as a major safety concern in ultra-high-field (UHF) Magnetic Resonance Imaging (MRI) applications. The calculation of local SAR requires the knowledge of the electric field induced by radiofrequency (RF) excitation, and the local electrical properties of tissues. Since electric field distribution cannot be directly mapped in conventional MR measurements, SAR estimation is usually performed using numerical model-based electromagnetic simulations which, however, are highly time consuming and cannot account for the specific anatomy and tissue properties of the subject undergoing a scan. In the present study, starting from the measurable RF magnetic fields (B1) in MRI, we conducted a series of mathematical deduction to estimate the local, voxel-wise and subject-specific SAR for each single coil element using a multi-channel transceiver array coil. We first evaluated the feasibility of this approach in numerical simulations including two different human head models. We further conducted experimental study in a physical phantom and in two human subjects at 7T using a multi-channel transceiver head coil. Accuracy of the results is discussed in the context of predicting local SAR in the human brain at UHF MRI using multi-channel RF transmission. PMID:23508259

  5. Proteomics analyses for the global proteins in the brain tissues of different human prion diseases.

    PubMed

    Shi, Qi; Chen, Li-Na; Zhang, Bao-Yun; Xiao, Kang; Zhou, Wei; Chen, Cao; Zhang, Xiao-Mei; Tian, Chan; Gao, Chen; Wang, Jing; Han, Jun; Dong, Xiao-Ping

    2015-04-01

    Proteomics changes of brain tissues have been described in different neurodegenerative diseases including Alzheimer's disease and Parkinson's disease. However, the brain proteomics of human prion disease remains less understood. In the study, the proteomics patterns of cortex and cerebellum of brain tissues of sporadic Creutzfeldt-Jakob disease, fatal familial insomnia, and G114V genetic CJD were analyzed with isobaric tags for relative and absolute quantitation combined with multidimensional liquid chromatography and MS analysis, with the brains from three normal individuals as controls. Global protein profiling, significant pathway, and functional categories were analyzed. In total, 2287 proteins were identified with quantitative information both in cortex and cerebellum regions. Cerebellum tissues appeared to contain more up- and down-regulated proteins (727 proteins) than cortex regions (312 proteins) of Creutzfeldt-Jakob disease, fatal familial insomnia, and G114V genetic CJD. Viral myocarditis, Parkinson's disease, Alzheimer's disease, lysosome, oxidative phosphorylation, protein export, and drug metabolism-cytochrome P450 were the most commonly affected pathways of the three kinds of diseases. Almost coincident biological functions were identified in the brain tissues of the three diseases. In all, data here demonstrate that the brain tissues of Creutzfeldt-Jakob disease, fatal familial insomnia, and G114V genetic CJD have obvious proteomics changes at their terminal stages, which show the similarities not only among human prion diseases but also with other neurodegeneration diseases. This is the first study to provide a reference proteome map for human prion diseases and will be helpful for future studies focused on potential biomarkers for the diagnosis and therapy of human prion diseases. © 2015 by The American Society for Biochemistry and Molecular Biology, Inc.

  6. fMRI evidence for areas that process surface gloss in the human visual cortex

    PubMed Central

    Sun, Hua-Chun; Ban, Hiroshi; Di Luca, Massimiliano; Welchman, Andrew E.

    2015-01-01

    Surface gloss is an important cue to the material properties of objects. Recent progress in the study of macaque’s brain has increased our understating of the areas involved in processing information about gloss, however the homologies with the human brain are not yet fully understood. Here we used human functional magnetic resonance imaging (fMRI) measurements to localize brain areas preferentially responding to glossy objects. We measured cortical activity for thirty-two rendered three-dimensional objects that had either Lambertian or specular surface properties. To control for differences in image structure, we overlaid a grid on the images and scrambled its cells. We found activations related to gloss in the posterior fusiform sulcus (pFs) and in area V3B/KO. Subsequent analysis with Granger causality mapping indicated that V3B/KO processes gloss information differently than pFs. Our results identify a small network of mid-level visual areas whose activity may be important in supporting the perception of surface gloss. PMID:25490434

  7. Ex vivo diffusion MRI of the human brain: Technical challenges and recent advances.

    PubMed

    Roebroeck, Alard; Miller, Karla L; Aggarwal, Manisha

    2018-06-04

    This review discusses ex vivo diffusion magnetic resonance imaging (dMRI) as an important research tool for neuroanatomical investigations and the validation of in vivo dMRI techniques, with a focus on the human brain. We review the challenges posed by the properties of post-mortem tissue, and discuss state-of-the-art tissue preparation methods and recent advances in pulse sequences and acquisition techniques to tackle these. We then review recent ex vivo dMRI studies of the human brain, highlighting the validation of white matter orientation estimates and the atlasing and mapping of large subcortical structures. We also give particular emphasis to the delineation of layered gray matter structure with ex vivo dMRI, as this application illustrates the strength of its mesoscale resolution over large fields of view. We end with a discussion and outlook on future and potential directions of the field. © 2018 The Authors. NMR in Biomedicine published by John Wiley & Sons Ltd.

  8. Persistent poliovirus infection of human fetal brain cells.

    PubMed

    Pavio, N; Buc-Caron, M H; Colbère-Garapin, F

    1996-09-01

    It has been suggested that poliovirus (PV), the causative agent of poliomyelitis, could persist in surviving patients. We have previously shown that PV can persistently infect some human cell lines in vitro, particularly neuroblastoma cell lines. We report here an ex vivo model in which PV can persistently infect primary cultures of human fetal brain cells. Two mutations involving capsid residues 142 of VP2 and 95 of VP1 were repeatedly selected during the persistent infections. These residues are located in capsid regions known to be involved in interactions between PV and its receptor. During the first week after infection, viral antigens were found in cells of both the neuronal and glial lineages. In contrast, 2 weeks after infection, viral antigens were detected almost exclusively in cells of the neuronal lineage. They were detected predominantly in cells expressing a marker of early commitment to the neuronal lineage, MAP-5, particularly in neuroblasts. Viral antigens were also found in immature progenitors expressing a neuroepithelium marker, nestin, and in cells expressing a marker of postmitotic neurons, MAP-2. The presence of viral antigens in postmitotic neurons suggests that PV can persist in neurons of patients who have survived poliomyelitis.

  9. Neuroscience thinks big (and collaboratively).

    PubMed

    Kandel, Eric R; Markram, Henry; Matthews, Paul M; Yuste, Rafael; Koch, Christof

    2013-09-01

    Despite cash-strapped times for research, several ambitious collaborative neuroscience projects have attracted large amounts of funding and media attention. In Europe, the Human Brain Project aims to develop a large-scale computer simulation of the brain, whereas in the United States, the Brain Activity Map is working towards establishing a functional connectome of the entire brain, and the Allen Institute for Brain Science has embarked upon a 10-year project to understand the mouse visual cortex (the MindScope project). US President Barack Obama's announcement of the BRAIN Initiative (Brain Research through Advancing Innovative Neurotechnologies Initiative) in April 2013 highlights the political commitment to neuroscience and is expected to further foster interdisciplinary collaborations, accelerate the development of new technologies and thus fuel much needed medical advances. In this Viewpoint article, five prominent neuroscientists explain the aims of the projects and how they are addressing some of the questions (and criticisms) that have arisen.

  10. Cortical Bases of Speech Perception: Evidence from Functional Lesion Studies

    ERIC Educational Resources Information Center

    Boatman, Dana

    2004-01-01

    Functional lesion studies have yielded new information about the cortical organization of speech perception in the human brain. We will review a number of recent findings, focusing on studies of speech perception that use the techniques of electrocortical mapping by cortical stimulation and hemispheric anesthetization by intracarotid amobarbital.…

  11. Brain metastases of breast cancer.

    PubMed

    Palmieri, Diane; Smith, Quentin R; Lockman, Paul R; Bronder, Julie; Gril, Brunilde; Chambers, Ann F; Weil, Robert J; Steeg, Patricia S

    Central nervous system or brain metastases traditionally occur in 10-16% of metastatic breast cancer patients and are associated with a dismal prognosis. The development of brain metastases has been associated with young age, and tumors that are estrogen receptor negative, Her-2+ or of the basal phenotype. Treatment typically includes whole brain irradiation, or either stereotactic radiosurgery or surgery with whole brain radiation, resulting in an approximately 20% one year survival. The blood-brain barrier is a formidable obstacle to the delivery of chemotherapeutics to the brain. Mouse experimental metastasis model systems have been developed for brain metastasis using selected sublines of human MDA-MB-231 breast carcinoma cells. Using micron sized iron particles and MRI imaging, the fate of MDA-MB-231BR cells has been mapped: Approximately 2% of injected cells form larger macroscopic metastases, while 5% of cells remain as dormant cells in the brain. New therapies with permeability for the blood-brain barrier are needed to counteract both types of tumor cells.

  12. Neuronal networks and mediators of cortical neurovascular coupling responses in normal and altered brain states.

    PubMed

    Lecrux, C; Hamel, E

    2016-10-05

    Brain imaging techniques that use vascular signals to map changes in neuronal activity, such as blood oxygenation level-dependent functional magnetic resonance imaging, rely on the spatial and temporal coupling between changes in neurophysiology and haemodynamics, known as 'neurovascular coupling (NVC)'. Accordingly, NVC responses, mapped by changes in brain haemodynamics, have been validated for different stimuli under physiological conditions. In the cerebral cortex, the networks of excitatory pyramidal cells and inhibitory interneurons generating the changes in neural activity and the key mediators that signal to the vascular unit have been identified for some incoming afferent pathways. The neural circuits recruited by whisker glutamatergic-, basal forebrain cholinergic- or locus coeruleus noradrenergic pathway stimulation were found to be highly specific and discriminative, particularly when comparing the two modulatory systems to the sensory response. However, it is largely unknown whether or not NVC is still reliable when brain states are altered or in disease conditions. This lack of knowledge is surprising since brain imaging is broadly used in humans and, ultimately, in conditions that deviate from baseline brain function. Using the whisker-to-barrel pathway as a model of NVC, we can interrogate the reliability of NVC under enhanced cholinergic or noradrenergic modulation of cortical circuits that alters brain states.This article is part of the themed issue 'Interpreting BOLD: a dialogue between cognitive and cellular neuroscience'. © 2016 The Author(s).

  13. High-resolution temporal and regional mapping of MAPT expression and splicing in human brain development.

    PubMed

    Hefti, Marco M; Farrell, Kurt; Kim, SoongHo; Bowles, Kathryn R; Fowkes, Mary E; Raj, Towfique; Crary, John F

    2018-01-01

    The microtubule associated protein tau plays a critical role in the pathogenesis of neurodegenerative disease. Recent studies suggest that tau also plays a role in disorders of neuronal connectivity, including epilepsy and post-traumatic stress disorder. Animal studies have shown that the MAPT gene, which codes for the tau protein, undergoes complex pre-mRNA alternative splicing to produce multiple isoforms during brain development. Human data, particularly on temporal and regional variation in tau splicing during development are however lacking. In this study, we present the first detailed examination of the temporal and regional sequence of MAPT alternative splicing in the developing human brain. We used a novel computational analysis of large transcriptomic datasets (total n = 502 patients), quantitative polymerase chain reaction (qPCR) and western blotting to examine tau expression and splicing in post-mortem human fetal, pediatric and adult brains. We found that MAPT exons 2 and 10 undergo abrupt shifts in expression during the perinatal period that are unique in the canonical human microtubule-associated protein family, while exon 3 showed small but significant temporal variation. Tau isoform expression may be a marker of neuronal maturation, temporally correlated with the onset of axonal growth. Immature brain regions such as the ganglionic eminence and rhombic lip had very low tau expression, but within more mature regions, there was little variation in tau expression or splicing. We thus demonstrate an abrupt, evolutionarily conserved shift in tau isoform expression during the human perinatal period that may be due to tau expression in maturing neurons. Alternative splicing of the MAPT pre-mRNA may play a vital role in normal brain development across multiple species and provides a basis for future investigations into the developmental and pathological functions of the tau protein.

  14. Whole-brain activity mapping onto a zebrafish brain atlas

    PubMed Central

    Randlett, Owen; Wee, Caroline L.; Naumann, Eva A.; Nnaemeka, Onyeka; Schoppik, David; Fitzgerald, James E.; Portugues, Ruben; Lacoste, Alix M.B.; Riegler, Clemens; Engert, Florian; Schier, Alexander F.

    2015-01-01

    In order to localize the neural circuits involved in generating behaviors, it is necessary to assign activity onto anatomical maps of the nervous system. Using brain registration across hundreds of larval zebrafish, we have built an expandable open source atlas containing molecular labels and anatomical region definitions, the Z-Brain. Using this platform and immunohistochemical detection of phosphorylated-Extracellular signal-regulated kinase (ERK/MAPK) as a readout of neural activity, we have developed a system to create and contextualize whole brain maps of stimulus- and behavior-dependent neural activity. This MAP-Mapping (Mitogen Activated Protein kinase – Mapping) assay is technically simple, fast, inexpensive, and data analysis is completely automated. Since MAP-Mapping is performed on fish that are freely swimming, it is applicable to nearly any stimulus or behavior. We demonstrate the utility of our high-throughput approach using hunting/feeding, pharmacological, visual and noxious stimuli. The resultant maps outline hundreds of areas associated with behaviors. PMID:26778924

  15. Acute functional reorganisation of the human motor cortex during resection of central lesions: a study using intraoperative brain mapping

    PubMed Central

    Duffau, H

    2001-01-01

    OBJECTIVES—Brain plasticity is supposed to allow the compensation of motor function in cases of rolandic lesion. The aim was to analyse the mechanisms of functional reorganisation during surgery in the central area.
METHODS—A motor brain mapping was performed in three right handed patients without any neurological deficit, operated on for a slow growing lesion near the rolandic region (two precentral resected under general anaesthesia and one retrocentral removed under local anaesthesia to allow also sensory mapping) using intraoperative direct electrical stimulations (5 mm space tips bipolar stimulator probe, biphasic square wave pulse current: 1 ms/phase, 60 Hz, 4 to 18mA).
RESULTS—For each patient, the motor areas of the hand and forearm in the primary motor cortex (M1) were identified before and after lesion removal with the same stimulation parameters: the same eloquent sites were found, plus the appearance after resection of additional sites in M1 inducing the same movement during stimulations as the previous areas.
CONCLUSIONS—Multiple cortical representations for hand and forearm movements in M1 seem to exist. In addition, the results demonstrate the short term capacity of the brain to make changes in local motor maps, by sudden unmasking after tumour resection of a second redundant site participating in the same movement. Finally, it seems not necessary for the whole of the redundant sites to be functional to provide normal movement, a concept with potential implications for surgery within the central region.

 PMID:11254775

  16. A new method for automated high-dimensional lesion segmentation evaluated in vascular injury and applied to the human occipital lobe.

    PubMed

    Mah, Yee-Haur; Jager, Rolf; Kennard, Christopher; Husain, Masud; Nachev, Parashkev

    2014-07-01

    Making robust inferences about the functional neuroanatomy of the brain is critically dependent on experimental techniques that examine the consequences of focal loss of brain function. Unfortunately, the use of the most comprehensive such technique-lesion-function mapping-is complicated by the need for time-consuming and subjective manual delineation of the lesions, greatly limiting the practicability of the approach. Here we exploit a recently-described general measure of statistical anomaly, zeta, to devise a fully-automated, high-dimensional algorithm for identifying the parameters of lesions within a brain image given a reference set of normal brain images. We proceed to evaluate such an algorithm in the context of diffusion-weighted imaging of the commonest type of lesion used in neuroanatomical research: ischaemic damage. Summary performance metrics exceed those previously published for diffusion-weighted imaging and approach the current gold standard-manual segmentation-sufficiently closely for fully-automated lesion-mapping studies to become a possibility. We apply the new method to 435 unselected images of patients with ischaemic stroke to derive a probabilistic map of the pattern of damage in lesions involving the occipital lobe, demonstrating the variation of anatomical resolvability of occipital areas so as to guide future lesion-function studies of the region. Copyright © 2012 Elsevier Ltd. All rights reserved.

  17. Influence of Fragrances on Human Psychophysiological Activity: With Special Reference to Human Electroencephalographic Response

    PubMed Central

    Sowndhararajan, Kandhasamy; Kim, Songmun

    2016-01-01

    The influence of fragrances such as perfumes and room fresheners on the psychophysiological activities of humans has been known for a long time, and its significance is gradually increasing in the medicinal and cosmetic industries. A fragrance consists of volatile chemicals with a molecular weight of less than 300 Da that humans perceive through the olfactory system. In humans, about 300 active olfactory receptor genes are devoted to detecting thousands of different fragrance molecules through a large family of olfactory receptors of a diverse protein sequence. The sense of smell plays an important role in the physiological effects of mood, stress, and working capacity. Electrophysiological studies have revealed that various fragrances affected spontaneous brain activities and cognitive functions, which are measured by an electroencephalograph (EEG). The EEG is a good temporal measure of responses in the central nervous system and it provides information about the physiological state of the brain both in health and disease. The EEG power spectrum is classified into different frequency bands such as delta (0.5–4 Hz), theta (4–8 Hz), alpha (8–13 Hz), beta (13–30 Hz) and gamma (30–50 Hz), and each band is correlated with different features of brain states. A quantitative EEG uses computer software to provide the topographic mapping of the brain activity in frontal, temporal, parietal and occipital brain regions. It is well known that decreases of alpha and beta activities and increases of delta and theta activities are associated with brain pathology and general cognitive decline. In the last few decades, many scientific studies were conducted to investigate the effect of inhalation of aroma on human brain functions. The studies have suggested a significant role for olfactory stimulation in the alteration of cognition, mood, and social behavior. This review aims to evaluate the available literature regarding the influence of fragrances on the psychophysiological activities of humans with special reference to EEG changes. PMID:27916830

  18. Detecting Large-Scale Brain Networks Using EEG: Impact of Electrode Density, Head Modeling and Source Localization

    PubMed Central

    Liu, Quanying; Ganzetti, Marco; Wenderoth, Nicole; Mantini, Dante

    2018-01-01

    Resting state networks (RSNs) in the human brain were recently detected using high-density electroencephalography (hdEEG). This was done by using an advanced analysis workflow to estimate neural signals in the cortex and to assess functional connectivity (FC) between distant cortical regions. FC analyses were conducted either using temporal (tICA) or spatial independent component analysis (sICA). Notably, EEG-RSNs obtained with sICA were very similar to RSNs retrieved with sICA from functional magnetic resonance imaging data. It still remains to be clarified, however, what technological aspects of hdEEG acquisition and analysis primarily influence this correspondence. Here we examined to what extent the detection of EEG-RSN maps by sICA depends on the electrode density, the accuracy of the head model, and the source localization algorithm employed. Our analyses revealed that the collection of EEG data using a high-density montage is crucial for RSN detection by sICA, but also the use of appropriate methods for head modeling and source localization have a substantial effect on RSN reconstruction. Overall, our results confirm the potential of hdEEG for mapping the functional architecture of the human brain, and highlight at the same time the interplay between acquisition technology and innovative solutions in data analysis. PMID:29551969

  19. Genetic effect of MTHFR C677T polymorphism on the structural covariance network and white-matter integrity in Alzheimer's disease.

    PubMed

    Chang, Yu-Tzu; Hsu, Shih-Wei; Tsai, Shih-Jen; Chang, Ya-Ting; Huang, Chi-Wei; Liu, Mu-En; Chen, Nai-Ching; Chang, Wen-Neng; Hsu, Jung-Lung; Lee, Chen-Chang; Chang, Chiung-Chih

    2017-06-01

    The 677 C to T transition in the MTHFR gene is a genetic determinant for hyperhomocysteinemia. We investigated whether this polymorphism modulates gray matter (GM) structural covariance networks independently of white-matter integrity in patients with Alzheimer's disease (AD). GM structural covariance networks were constructed by 3D T1-magnetic resonance imaging and seed-based analysis. The patients were divided into two genotype groups: C homozygotes (n = 73) and T carriers (n = 62). Using diffusion tensor imaging and white-matter parcellation, 11 fiber bundle integrities were compared between the two genotype groups. Cognitive test scores were the major outcome factors. The T carriers had higher homocysteine levels, lower posterior cingulate cortex GM volume, and more clusters in the dorsal medial lobe subsystem showing stronger covariance strength. Both posterior cingulate cortex seed and interconnected peak cluster volumes predicted cognitive test scores, especially in the T carriers. There were no between-group differences in fiber tract diffusion parameters. The MTHFR 677T polymorphism modulates posterior cingulate cortex-anchored structural covariance strength independently of white matter integrities. Hum Brain Mapp 38:3039-3051, 2017. © 2017 The Authors Human Brain Mapping Published Wiley by Periodicals, Inc. © 2017 The Authors Human Brain Mapping Published Wiley by Periodicals, Inc.

  20. fMRI mapping of the visual system in the mouse brain with interleaved snapshot GE-EPI.

    PubMed

    Niranjan, Arun; Christie, Isabel N; Solomon, Samuel G; Wells, Jack A; Lythgoe, Mark F

    2016-10-01

    The use of functional magnetic resonance imaging (fMRI) in mice is increasingly prevalent, providing a means to non-invasively characterise functional abnormalities associated with genetic models of human diseases. The predominant stimulus used in task-based fMRI in the mouse is electrical stimulation of the paw. Task-based fMRI in mice using visual stimuli remains underexplored, despite visual stimuli being common in human fMRI studies. In this study, we map the mouse brain visual system with BOLD measurements at 9.4T using flashing light stimuli with medetomidine anaesthesia. BOLD responses were observed in the lateral geniculate nucleus, the superior colliculus and the primary visual area of the cortex, and were modulated by the flashing frequency, diffuse vs focussed light and stimulus context. Negative BOLD responses were measured in the visual cortex at 10Hz flashing frequency; but turned positive below 5Hz. In addition, the use of interleaved snapshot GE-EPI improved fMRI image quality without diminishing the temporal contrast-noise-ratio. Taken together, this work demonstrates a novel methodological protocol in which the mouse brain visual system can be non-invasively investigated using BOLD fMRI. Copyright © 2016 The Authors. Published by Elsevier Inc. All rights reserved.

  1. Slice-to-Volume Nonrigid Registration of Histological Sections to MR Images of the Human Brain

    PubMed Central

    Osechinskiy, Sergey; Kruggel, Frithjof

    2011-01-01

    Registration of histological images to three-dimensional imaging modalities is an important step in quantitative analysis of brain structure, in architectonic mapping of the brain, and in investigation of the pathology of a brain disease. Reconstruction of histology volume from serial sections is a well-established procedure, but it does not address registration of individual slices from sparse sections, which is the aim of the slice-to-volume approach. This study presents a flexible framework for intensity-based slice-to-volume nonrigid registration algorithms with a geometric transformation deformation field parametrized by various classes of spline functions: thin-plate splines (TPS), Gaussian elastic body splines (GEBS), or cubic B-splines. Algorithms are applied to cross-modality registration of histological and magnetic resonance images of the human brain. Registration performance is evaluated across a range of optimization algorithms and intensity-based cost functions. For a particular case of histological data, best results are obtained with a TPS three-dimensional (3D) warp, a new unconstrained optimization algorithm (NEWUOA), and a correlation-coefficient-based cost function. PMID:22567290

  2. Statistical parametric mapping of stimuli-evoked changes in quantitative blood flow using extended-focus optical coherence microscopy (Conference Presentation)

    NASA Astrophysics Data System (ADS)

    Marchand, Paul J.; Bouwens, Arno; Shamaei, Vincent; Nguyen, David; Extermann, Jerome; Bolmont, Tristan; Lasser, Theo

    2016-03-01

    Magnetic Resonance Imaging has revolutionised our understanding of brain function through its ability to image human cerebral structures non-invasively over the entire brain. By exploiting the different magnetic properties of oxygenated and deoxygenated blood, functional MRI can indirectly map areas undergoing neural activation. Alongside the development of fMRI, powerful statistical tools have been developed in an effort to shed light on the neural pathways involved in processing of sensory and cognitive information. In spite of the major improvements made in fMRI technology, the obtained spatial resolution of hundreds of microns prevents MRI in resolving and monitoring processes occurring at the cellular level. In this regard, Optical Coherence Microscopy is an ideal instrumentation as it can image at high spatio-temporal resolution. Moreover, by measuring the mean and the width of the Doppler spectra of light scattered by moving particles, OCM allows extracting the axial and lateral velocity components of red blood cells. The ability to assess quantitatively total blood velocity, as opposed to classical axial velocity Doppler OCM, is of paramount importance in brain imaging as a large proportion of cortical vascular is oriented perpendicularly to the optical axis. We combine here quantitative blood flow imaging with extended-focus Optical Coherence Microscopy and Statistical Parametric Mapping tools to generate maps of stimuli-evoked cortical hemodynamics at the capillary level.

  3. 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.

  4. Spatial Hyperschematia without Spatial Neglect after Insulo-Thalamic Disconnection

    PubMed Central

    Saj, Arnaud; Wilcke, Juliane C.; Gschwind, Markus; Emond, Héloïse; Assal, Frédéric

    2013-01-01

    Different spatial representations are not stored as a single multipurpose map in the brain. Right brain-damaged patients can show a distortion, a compression of peripersonal and extrapersonal space. Here we report the case of a patient with a right insulo-thalamic disconnection without spatial neglect. The patient, compared with 10 healthy control subjects, showed a constant and reliable increase of her peripersonal and extrapersonal egocentric space representations - that we named spatial hyperschematia - yet left her allocentric space representations intact. This striking dissociation shows that our interactions with the surrounding world are represented and processed modularly in the human brain, depending on their frame of reference. PMID:24302992

  5. Three-dimensional functional magnetic resonance imaging of human brain on a clinical 1.5-T scanner.

    PubMed Central

    van Gelderen, P; Ramsey, N F; Liu, G; Duyn, J H; Frank, J A; Weinberger, D R; Moonen, C T

    1995-01-01

    Functional magnetic resonance imaging (fMRI) is a tool for mapping brain function that utilizes neuronal activity-induced changes in blood oxygenation. An efficient three-dimensional fMRI method is presented for imaging brain activity on conventional, widely available, 1.5-T scanners, without additional hardware. This approach uses large magnetic susceptibility weighting based on the echo-shifting principle combined with multiple gradient echoes per excitation. Motor stimulation, induced by self-paced finger tapping, reliably produced significant signal increase in the hand region of the contralateral primary motor cortex in every subject tested. Images Fig. 2 Fig. 3 PMID:7624341

  6. [Multiplexing mapping of human cDNAs]. Final report, September 1, 1991--February 28, 1994

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

    Not Available

    Using PCR with automated product analysis, 329 human brain cDNA sequences have been assigned to individual human chromosomes. Primers were designed from single-pass cDNA sequences expressed sequence tags (ESTs). Primers were used in PCR reactions with DNA from somatic cell hybrid mapping panels as templates, often with multiplexing. Many ESTs mapped match sequence database records. To evaluate of these matches, the position of the primers relative to the matching region (In), the BLAST scores and the Poisson probability values of the EST/sequence record match were determined. In cases where the gene product was stringently identified by the sequence match hadmore » already been mapped, the gene locus determined by EST was consistent with the previous position which strongly supports the validity of assigning unknown genes to human chromosomes based on the EST sequence matches. In the present cases mapping the ESTs to a chromosome can also be considered to have mapped the known gene product: rolipram-sensitive cAMP phosphodiesterase, chromosome 1; protein phosphatase 2A{beta}, chromosome 4; alpha-catenin, chromosome 5; the ELE1 oncogene, chromosome 10q11.2 or q2.1-q23; MXII protein, chromosome l0q24-qter; ribosomal protein L18a homologue, chromosome 14; ribosomal protein L3, chromosome 17; and moesin, Xp11-cen. There were also ESTs mapped that were closely related to non-human sequence records. These matches therefore can be considered to identify human counterparts of known gene products, or members of known gene families. Examples of these include membrane proteins, translation-associated proteins, structural proteins, and enzymes. These data then demonstrate that single pass sequence information is sufficient to design PCR primers useful for assigning cDNA sequences to human chromosomes. When the EST sequence matches previous sequence database records, the chromosome assignments of the EST can be used to make preliminary assignments of the human gene to a chromosome.« less

  7. Stomach-brain synchrony reveals a novel, delayed-connectivity resting-state network in humans

    PubMed Central

    Devauchelle, Anne-Dominique; Béranger, Benoît; Tallon-Baudry, Catherine

    2018-01-01

    Resting-state networks offer a unique window into the brain’s functional architecture, but their characterization remains limited to instantaneous connectivity thus far. Here, we describe a novel resting-state network based on the delayed connectivity between the brain and the slow electrical rhythm (0.05 Hz) generated in the stomach. The gastric network cuts across classical resting-state networks with partial overlap with autonomic regulation areas. This network is composed of regions with convergent functional properties involved in mapping bodily space through touch, action or vision, as well as mapping external space in bodily coordinates. The network is characterized by a precise temporal sequence of activations within a gastric cycle, beginning with somato-motor cortices and ending with the extrastriate body area and dorsal precuneus. Our results demonstrate that canonical resting-state networks based on instantaneous connectivity represent only one of the possible partitions of the brain into coherent networks based on temporal dynamics. PMID:29561263

  8. A Proteomics Analysis of the Effects of Chronic Hemiparetic Stroke on Troponin T Expression in Human Vastus Lateralis

    PubMed Central

    Rabek, Jeffrey P.; Hafer-Macko, Charlene E.; Amaning, James K.; DeFord, James H.; Dimayuga, Vincent L.; Madsen, Mark A.; Macko, Richard F.

    2009-01-01

    Stroke disability is attributed to upper motor neuron deficits resulting from ischemic brain injury. We have developed proteome maps of the Vastus lateralis to examine the effects of ischemic brain injury on paretic skeletal muscle myofilament proteins. Proteomics analyses from seven hemiparetic stroke patients have detected a decrease of three troponin T isoforms in the paretic muscle suggesting that myosin–actin interactions may be attenuated. We propose that ischemic brain injury may prevent troponin T participation in complex formation thereby affecting the protein interactions associated with excitation–contraction coupling. We have also detected a novel skeletal troponin T isoform that has a C-terminal variation. Our data suggest that the decreased slow troponin T isoform pools in the paretic limb may contribute to the gait deficit after stroke. The complexity of the neurological deficit on Vastus lateralis is suggested by the multiple changes in proteins detected by our proteomics mapping. PMID:19447848

  9. A super-resolution ultrasound method for brain vascular mapping

    PubMed Central

    O'Reilly, Meaghan A.; Hynynen, Kullervo

    2013-01-01

    Purpose: High-resolution vascular imaging has not been achieved in the brain due to limitations of current clinical imaging modalities. The authors present a method for transcranial ultrasound imaging of single micrometer-size bubbles within a tube phantom. Methods: Emissions from single bubbles within a tube phantom were mapped through an ex vivo human skull using a sparse hemispherical receiver array and a passive beamforming algorithm. Noninvasive phase and amplitude correction techniques were applied to compensate for the aberrating effects of the skull bone. The positions of the individual bubbles were estimated beyond the diffraction limit of ultrasound to produce a super-resolution image of the tube phantom, which was compared with microcomputed tomography (micro-CT). Results: The resulting super-resolution ultrasound image is comparable to results obtained via the micro-CT for small tissue specimen imaging. Conclusions: This method provides superior resolution to deep-tissue contrast ultrasound and has the potential to be extended to provide complete vascular network imaging in the brain. PMID:24320408

  10. Repeated mapping of cortical language sites by preoperative navigated transcranial magnetic stimulation compared to repeated intraoperative DCS mapping in awake craniotomy

    PubMed Central

    2014-01-01

    Background Repetitive navigated transcranial magnetic stimulation (rTMS) was recently described for mapping of human language areas. However, its capability of detecting language plasticity in brain tumor patients was not proven up to now. Thus, this study was designed to evaluate such data in order to compare rTMS language mapping to language mapping during repeated awake surgery during follow-up in patients suffering from language-eloquent gliomas. Methods Three right-handed patients with left-sided gliomas (2 opercular glioblastomas, 1 astrocytoma WHO grade III of the angular gyrus) underwent preoperative language mapping by rTMS as well as intraoperative language mapping provided via direct cortical stimulation (DCS) for initial as well as for repeated Resection 7, 10, and 15 months later. Results Overall, preoperative rTMS was able to elicit clear language errors in all mappings. A good correlation between initial rTMS and DCS results was observed. As a consequence of brain plasticity, initial DCS and rTMS findings only corresponded with the results obtained during the second examination in one out of three patients thus suggesting changes of language organization in two of our three patients. Conclusions This report points out the usefulness but also the limitations of preoperative rTMS language mapping to detect plastic changes in language function or for long-term follow-up prior to DCS even in recurrent gliomas. However, DCS still has to be regarded as gold standard. PMID:24479694

  11. Using Data-Driven Model-Brain Mappings to Constrain Formal Models of Cognition

    PubMed Central

    Borst, Jelmer P.; Nijboer, Menno; Taatgen, Niels A.; van Rijn, Hedderik; Anderson, John R.

    2015-01-01

    In this paper we propose a method to create data-driven mappings from components of cognitive models to brain regions. Cognitive models are notoriously hard to evaluate, especially based on behavioral measures alone. Neuroimaging data can provide additional constraints, but this requires a mapping from model components to brain regions. Although such mappings can be based on the experience of the modeler or on a reading of the literature, a formal method is preferred to prevent researcher-based biases. In this paper we used model-based fMRI analysis to create a data-driven model-brain mapping for five modules of the ACT-R cognitive architecture. We then validated this mapping by applying it to two new datasets with associated models. The new mapping was at least as powerful as an existing mapping that was based on the literature, and indicated where the models were supported by the data and where they have to be improved. We conclude that data-driven model-brain mappings can provide strong constraints on cognitive models, and that model-based fMRI is a suitable way to create such mappings. PMID:25747601

  12. A commonly carried allele of the obesity-related FTO gene is associated with reduced brain volume in the healthy elderly

    PubMed Central

    Stein, Jason L.; Hua, Xue; Lee, Suh; Hibar, Derrek P.; Leow, Alex D.; Dinov, Ivo D.; Toga, Arthur W.; Saykin, Andrew J.; Shen, Li; Foroud, Tatiana; Pankratz, Nathan; Huentelman, Matthew J.; Craig, David W.; Gerber, Jill D.; Allen, April N.; Corneveaux, Jason J.; Stephan, Dietrich A.; DeCarli, Charles S.; DeChairo, Bryan M.; Potkin, Steven G.; Jack, Clifford R.; Weiner, Michael W.; Raji, Cyrus A.; Lopez, Oscar L.; Becker, James T.; Carmichael, Owen T.; Thompson, Paul M.; Weiner, Michael; Thal, Leon; Petersen, Ronald; Jack, Clifford R.; Jagust, William; Trojanowki, John; Toga, Arthur W.; Beckett, Laurel; Green, Robert C.; Gamst, Anthony; Potter, William Z.; Montine, Tom; Anders, Dale; Bernstein, Matthew; Felmlee, Joel; Fox, Nick; Thompson, Paul; Schuff, Norbert; Alexander, Gene; Bandy, Dan; Koeppe, Robert A.; Foster, Norm; Reiman, Eric M.; Chen, Kewei; Trojanowki, John; Shaw, Les; Lee, Virginia M.-Y.; Korecka, Magdalena; Toga, Arthur W.; Crawford, Karen; Neu, Scott; Harvey, Danielle; Gamst, Anthony; Kornak, John; Kachaturian, Zaven; Frank, Richard; Snyder, Peter J.; Molchan, Susan; Kaye, Jeffrey; Vorobik, Remi; Quinn, Joseph; Schneider, Lon; Pawluczyk, Sonia; Spann, Bryan; Fleisher, Adam S.; Vanderswag, Helen; Heidebrink, Judith L.; Lord, Joanne L.; Johnson, Kris; Doody, Rachelle S.; Villanueva-Meyer, Javier; Chowdhury, Munir; Stern, Yaakov; Honig, Lawrence S.; Bell, Karen L.; Morris, John C.; Mintun, Mark A.; Schneider, Stacy; Marson, Daniel; Griffith, Randall; Badger, Beverly; Grossman, Hillel; Tang, Cheuk; Stern, Jessica; deToledo-Morrell, Leyla; Shah, Raj C.; Bach, Julie; Duara, Ranjan; Isaacson, Richard; Strauman, Silvia; Albert, Marilyn S.; Pedroso, Julia; Toroney, Jaimie; Rusinek, Henry; de Leon, Mony J; De Santi, Susan M; Doraiswamy, P. Murali; Petrella, Jeffrey R.; Aiello, Marilyn; Clark, Christopher M.; Pham, Cassie; Nunez, Jessica; Smith, Charles D.; Given II, Curtis A.; Hardy, Peter; DeKosky, Steven T.; Oakley, MaryAnn; Simpson, Donna M.; Ismail, M. Saleem; Porsteinsson, Anton; McCallum, Colleen; Cramer, Steven C.; Mulnard, Ruth A.; McAdams-Ortiz, Catherine; Diaz-Arrastia, Ramon; Martin-Cook, Kristen; DeVous, Michael; Levey, Allan I.; Lah, James J.; Cellar, Janet S.; Burns, Jeffrey M.; Anderson, Heather S.; Laubinger, Mary M.; Bartzokis, George; Silverman, Daniel H.S.; Lu, Po H.; Fletcher, Rita; Parfitt, Francine; Johnson, Heather; Farlow, Martin; Herring, Scott; Hake, Ann M.; van Dyck, Christopher H.; MacAvoy, Martha G.; Bifano, Laurel A.; Chertkow, Howard; Bergman, Howard; Hosein, Chris; Black, Sandra; Graham, Simon; Caldwell, Curtis; Feldman, Howard; Assaly, Michele; Hsiung, Ging-Yuek R.; Kertesz, Andrew; Rogers, John; Trost, Dick; Bernick, Charles; Gitelman, Darren; Johnson, Nancy; Mesulam, Marsel; Sadowsky, Carl; Villena, Teresa; Mesner, Scott; Aisen, Paul S.; Johnson, Kathleen B.; Behan, Kelly E.; Sperling, Reisa A.; Rentz, Dorene M.; Johnson, Keith A.; Rosen, Allyson; Tinklenberg, Jared; Ashford, Wes; Sabbagh, Marwan; Connor, Donald; Obradov, Sanja; Killiany, Ron; Norbash, Alex; Obisesan, Thomas O.; Jayam-Trouth, Annapurni; Wang, Paul; Auchus, Alexander P.; Huang, Juebin; Friedland, Robert P.; DeCarli, Charles; Fletcher, Evan; Carmichael, Owen; Kittur, Smita; Mirje, Seema; Johnson, Sterling C.; Borrie, Michael; Lee, T-Y; Asthana, Sanjay; Carlsson, Cynthia M.; Potkin, Steven G.; Highum, Diane; Preda, Adrian; Nguyen, Dana; Tariot, Pierre N.; Hendin, Barry A.; Scharre, Douglas W.; Kataki, Maria; Beversdorf, David Q.; Zimmerman, Earl A.; Celmins, Dzintra; Brown, Alice D.; Gandy, Sam; Marenberg, Marjorie E.; Rovner, Barry W.; Pearlson, Godfrey; Blank, Karen; Anderson, Karen; Saykin, Andrew J.; Santulli, Robert B.; Pare, Nadia; Williamson, Jeff D.; Sink, Kaycee M.; Potter, Huntington; Ashok Raj, B.; Giordano, Amy; Ott, Brian R.; Wu, Chuang-Kuo; Cohen, Ronald; Wilks, Kerri L.

    2010-01-01

    A recently identified variant within the fat mass and obesity-associated (FTO) gene is carried by 46% of Western Europeans and is associated with an ~1.2 kg higher weight, on average, in adults and an ~1 cm greater waist circumference. With >1 billion overweight and 300 million obese persons worldwide, it is crucial to understand the implications of carrying this very common allele for the health of our aging population. FTO is highly expressed in the brain and elevated body mass index (BMI) is associated with brain atrophy, but it is unknown how the obesity-associated risk allele affects human brain structure. We therefore generated 3D maps of regional brain volume differences in 206 healthy elderly subjects scanned with MRI and genotyped as part of the Alzheimer's Disease Neuroimaging Initiative. We found a pattern of systematic brain volume deficits in carriers of the obesity-associated risk allele versus noncarriers. Relative to structure volumes in the mean template, FTO risk allele carriers versus noncarriers had an average brain volume difference of ~8% in the frontal lobes and 12% in the occipital lobes—these regions also showed significant volume deficits in subjects with higher BMI. These brain differences were not attributable to differences in cholesterol levels, hypertension, or the volume of white matter hyperintensities; which were not detectably higher in FTO risk allele carriers versus noncarriers. These brain maps reveal that a commonly carried susceptibility allele for obesity is associated with structural brain atrophy, with implications for the health of the elderly. PMID:20404173

  13. A commonly carried allele of the obesity-related FTO gene is associated with reduced brain volume in the healthy elderly.

    PubMed

    Ho, April J; Stein, Jason L; Hua, Xue; Lee, Suh; Hibar, Derrek P; Leow, Alex D; Dinov, Ivo D; Toga, Arthur W; Saykin, Andrew J; Shen, Li; Foroud, Tatiana; Pankratz, Nathan; Huentelman, Matthew J; Craig, David W; Gerber, Jill D; Allen, April N; Corneveaux, Jason J; Stephan, Dietrich A; DeCarli, Charles S; DeChairo, Bryan M; Potkin, Steven G; Jack, Clifford R; Weiner, Michael W; Raji, Cyrus A; Lopez, Oscar L; Becker, James T; Carmichael, Owen T; Thompson, Paul M

    2010-05-04

    A recently identified variant within the fat mass and obesity-associated (FTO) gene is carried by 46% of Western Europeans and is associated with an approximately 1.2 kg higher weight, on average, in adults and an approximately 1 cm greater waist circumference. With >1 billion overweight and 300 million obese persons worldwide, it is crucial to understand the implications of carrying this very common allele for the health of our aging population. FTO is highly expressed in the brain and elevated body mass index (BMI) is associated with brain atrophy, but it is unknown how the obesity-associated risk allele affects human brain structure. We therefore generated 3D maps of regional brain volume differences in 206 healthy elderly subjects scanned with MRI and genotyped as part of the Alzheimer's Disease Neuroimaging Initiative. We found a pattern of systematic brain volume deficits in carriers of the obesity-associated risk allele versus noncarriers. Relative to structure volumes in the mean template, FTO risk allele carriers versus noncarriers had an average brain volume difference of approximately 8% in the frontal lobes and 12% in the occipital lobes-these regions also showed significant volume deficits in subjects with higher BMI. These brain differences were not attributable to differences in cholesterol levels, hypertension, or the volume of white matter hyperintensities; which were not detectably higher in FTO risk allele carriers versus noncarriers. These brain maps reveal that a commonly carried susceptibility allele for obesity is associated with structural brain atrophy, with implications for the health of the elderly.

  14. The 2007 Feinberg lecture: a new road map for neuroprotection.

    PubMed

    Donnan, Geoffrey A

    2008-01-01

    There have now been numerous phase III trials of neuroprotection that have failed to live up to the expectations created by preclinical testing in animal models, the most recent of which was the second pivotal trial of the spin trap agent NXY-059. We have reached a stage at which research in this area should stop altogether or radical new approaches adopted. The purpose of this article is to review how we reached this stage and make recommendations for a new approach to neuroprotection research. The background to neuroprotection research is reviewed and its problems are highlighted based on the research of others and of our own research group. From this, a series of questions are posed that require answers if the field is to progress. A road map for future research is then proposed. The road map involves the following steps for putative neuroprotectants: (1) better proof of efficacy in animal models; (2) in vivo evidence of efficacy in human tissue using cell cultures or brain slices; (3) in vivo studies of their distribution in the normal and ischemic human brain, particularly focusing on the ischemic penumbra; (4) demonstration of efficacy in novel human models of cerebral ischemia; and (5) phase II and III clinical trails with penumbral selection using imaging techniques. The accumulated evidence suggests that neuroprotection failure in clinical trial is due to identifiable preclinical and clinical factors. Neuroprotection research should be pursued but with a very different and more rigorous approach.

  15. Imaging human brain cyto- and myelo-architecture with quantitative OCT (Conference Presentation)

    NASA Astrophysics Data System (ADS)

    Boas, David A.; Wang, Hui; Konukoglu, Ender; Fischl, Bruce; Sakadzic, Sava; Magnain, Caroline V.

    2017-02-01

    No current imaging technology allows us to directly and without significant distortion visualize the microscopic and defining anatomical features of the human brain. Ex vivo histological techniques can yield exquisite planar images, but the cutting, mounting and staining that are required components of this type of imaging induce distortions that are different for each slice, introducing cross-slice differences that prohibit true 3D analysis. We are overcoming this issue by utilizing Optical Coherence Tomography (OCT) with the goal to image whole human brain cytoarchitectural and laminar properties with potentially 3.5 µm resolution in block-face without the need for exogenous staining. From the intrinsic scattering contrast of the brain tissue, OCT gives us images that are comparable to Nissl stains, but without the distortions introduced in standard histology as the OCT images are acquired from the block face prior to slicing and thus without the need for subsequent staining and mounting. We have shown that laminar and cytoarchitectural properties of the brain can be characterized with OCT just as well as with Nissl staining. We will present our recent advances to improve the axial resolution while maintaining contrast; improvements afforded by speckle reduction procedures; and efforts to obtain quantitative maps of the optical scattering coefficient, an intrinsic property of the tissue.

  16. Brain Injury Lesion Imaging Using Preconditioned Quantitative Susceptibility Mapping without Skull Stripping.

    PubMed

    Soman, S; Liu, Z; Kim, G; Nemec, U; Holdsworth, S J; Main, K; Lee, B; Kolakowsky-Hayner, S; Selim, M; Furst, A J; Massaband, P; Yesavage, J; Adamson, M M; Spincemallie, P; Moseley, M; Wang, Y

    2018-04-01

    Identifying cerebral microhemorrhage burden can aid in the diagnosis and management of traumatic brain injury, stroke, hypertension, and cerebral amyloid angiopathy. MR imaging susceptibility-based methods are more sensitive than CT for detecting cerebral microhemorrhage, but methods other than quantitative susceptibility mapping provide results that vary with field strength and TE, require additional phase maps to distinguish blood from calcification, and depict cerebral microhemorrhages as bloom artifacts. Quantitative susceptibility mapping provides universal quantification of tissue magnetic property without these constraints but traditionally requires a mask generated by skull-stripping, which can pose challenges at tissue interphases. We evaluated the preconditioned quantitative susceptibility mapping MR imaging method, which does not require skull-stripping, for improved depiction of brain parenchyma and pathology. Fifty-six subjects underwent brain MR imaging with a 3D multiecho gradient recalled echo acquisition. Mask-based quantitative susceptibility mapping images were created using a commonly used mask-based quantitative susceptibility mapping method, and preconditioned quantitative susceptibility images were made using precondition-based total field inversion. All images were reviewed by a neuroradiologist and a radiology resident. Ten subjects (18%), all with traumatic brain injury, demonstrated blood products on 3D gradient recalled echo imaging. All lesions were visible on preconditioned quantitative susceptibility mapping, while 6 were not visible on mask-based quantitative susceptibility mapping. Thirty-one subjects (55%) demonstrated brain parenchyma and/or lesions that were visible on preconditioned quantitative susceptibility mapping but not on mask-based quantitative susceptibility mapping. Six subjects (11%) demonstrated pons artifacts on preconditioned quantitative susceptibility mapping and mask-based quantitative susceptibility mapping; they were worse on preconditioned quantitative susceptibility mapping. Preconditioned quantitative susceptibility mapping MR imaging can bring the benefits of quantitative susceptibility mapping imaging to clinical practice without the limitations of mask-based quantitative susceptibility mapping, especially for evaluating cerebral microhemorrhage-associated pathologies, such as traumatic brain injury. © 2018 by American Journal of Neuroradiology.

  17. Brain structural plasticity with spaceflight.

    PubMed

    Koppelmans, Vincent; Bloomberg, Jacob J; Mulavara, Ajitkumar P; Seidler, Rachael D

    2016-01-01

    Humans undergo extensive sensorimotor adaptation during spaceflight due to altered vestibular inputs and body unloading. No studies have yet evaluated the effects of spaceflight on human brain structure despite the fact that recently reported optic nerve structural changes are hypothesized to occur due to increased intracranial pressure occurring with microgravity. This is the first report on human brain structural changes with spaceflight. We evaluated retrospective longitudinal T2-weighted MRI scans and balance data from 27 astronauts (thirteen ~2-week shuttle crew members and fourteen ~6-month International Space Station crew members) to determine spaceflight effects on brain structure, and whether any pre to postflight brain changes are associated with balance changes. Data were obtained from the NASA Lifetime Surveillance of Astronaut Health. Brain scans were segmented into gray matter maps and normalized into MNI space using a stepwise approach through subject specific templates. Non-parametric permutation testing was used to analyze pre to postflight volumetric gray matter changes. We found extensive volumetric gray matter decreases, including large areas covering the temporal and frontal poles and around the orbits. This effect was larger in International Space Station versus shuttle crew members in some regions. There were bilateral focal gray matter increases within the medial primary somatosensory and motor cortex; i.e., the cerebral areas where the lower limbs are represented. These intriguing findings are observed in a retrospective data set; future prospective studies should probe the underlying mechanisms and behavioral consequences.

  18. 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).

  19. No inherent left and right side in human 'mental number line': evidence from right brain damage.

    PubMed

    Aiello, Marilena; Jacquin-Courtois, Sophie; Merola, Sheila; Ottaviani, Teresa; Tomaiuolo, Francesco; Bueti, Domenica; Rossetti, Yves; Doricchi, Fabrizio

    2012-08-01

    Spatial reasoning has a relevant role in mathematics and helps daily computational activities. It is widely assumed that in cultures with left-to-right reading, numbers are organized along the mental equivalent of a ruler, the mental number line, with small magnitudes located to the left of larger ones. Patients with right brain damage can disregard smaller numbers while mentally setting the midpoint of number intervals. This has been interpreted as a sign of spatial neglect for numbers on the left side of the mental number line and taken as a strong argument for the intrinsic left-to-right organization of the mental number line. Here, we put forward the understanding of this cognitive disability by discovering that patients with right brain damage disregard smaller numbers both when these are mapped on the left side of the mental number line and on the right side of an imagined clock face. This shows that the right hemisphere supports the representation of small numerical magnitudes independently from their mapping on the left or the right side of a spatial-mental layout. In addition, the study of the anatomical correlates through voxel-based lesion-symptom mapping and the mapping of lesion peaks on the diffusion tensor imaging-based reconstruction of white matter pathways showed that the rightward bias in the imagined clock-face was correlated with lesions of high-level middle temporal visual areas that code stimuli in object-centred spatial coordinates, i.e. stimuli that, like a clock face, have an inherent left and right side. In contrast, bias towards higher numbers on the mental number line was linked to white matter damage in the frontal component of the parietal-frontal number network. These anatomical findings show that the human brain does not represent the mental number line as an object with an inherent left and right side. We conclude that the bias towards higher numbers in the mental bisection of number intervals does not depend on left side spatial, imagery or object-centred neglect and that it rather depends on disruption of an abstract non-spatial representation of small numerical magnitudes.

  20. Maps and streams in the auditory cortex: nonhuman primates illuminate human speech processing

    PubMed Central

    Rauschecker, Josef P; Scott, Sophie K

    2010-01-01

    Speech and language are considered uniquely human abilities: animals have communication systems, but they do not match human linguistic skills in terms of recursive structure and combinatorial power. Yet, in evolution, spoken language must have emerged from neural mechanisms at least partially available in animals. In this paper, we will demonstrate how our understanding of speech perception, one important facet of language, has profited from findings and theory in nonhuman primate studies. Chief among these are physiological and anatomical studies showing that primate auditory cortex, across species, shows patterns of hierarchical structure, topographic mapping and streams of functional processing. We will identify roles for different cortical areas in the perceptual processing of speech and review functional imaging work in humans that bears on our understanding of how the brain decodes and monitors speech. A new model connects structures in the temporal, frontal and parietal lobes linking speech perception and production. PMID:19471271

  1. Quantifying Mesoscale Neuroanatomy Using X-Ray Microtomography

    PubMed Central

    Gray Roncal, William; Prasad, Judy A.; Fernandes, Hugo L.; Gürsoy, Doga; De Andrade, Vincent; Fezzaa, Kamel; Xiao, Xianghui; Vogelstein, Joshua T.; Jacobsen, Chris; Körding, Konrad P.

    2017-01-01

    Methods for resolving the three-dimensional (3D) microstructure of the brain typically start by thinly slicing and staining the brain, followed by imaging numerous individual sections with visible light photons or electrons. In contrast, X-rays can be used to image thick samples, providing a rapid approach for producing large 3D brain maps without sectioning. Here we demonstrate the use of synchrotron X-ray microtomography (µCT) for producing mesoscale (∼1 µm 3 resolution) brain maps from millimeter-scale volumes of mouse brain. We introduce a pipeline for µCT-based brain mapping that develops and integrates methods for sample preparation, imaging, and automated segmentation of cells, blood vessels, and myelinated axons, in addition to statistical analyses of these brain structures. Our results demonstrate that X-ray tomography achieves rapid quantification of large brain volumes, complementing other brain mapping and connectomics efforts. PMID:29085899

  2. What the cognitive neurosciences mean to me.

    PubMed

    Pereira, Alfredo

    2007-01-01

    Cognitive Neuroscience is an interdisciplinary area of research that combines measurement of brain activity (mostly by means of neuroimaging) with a simultaneous performance of cognitive tasks by human subjects. These investigations have been successful in the task of connecting the sciences of the brain (Neurosciences) and the sciences of the mind (Cognitive Sciences). Advances on this kind of research provide a map of localization of cognitive functions in the human brain. Do these results help us to understand how mind relates to the brain? In my view, the results obtained by the Cognitive Neurosciences lead to new investigations in the domain of Molecular Neurobiology, aimed at discovering biophysical mechanisms that generate the activity measured by neuroimaging instruments. In this context, I argue that the understanding of how ionic/molecular processes support cognition and consciousness cannot be made by means of the standard reductionist explanations. Knowledge of ionic/molecular mechanisms can contribute to our understanding of the human mind as long as we assume an alternative form of explanation, based on psycho-physical similarities, together with an ontological view of mentality and spirituality as embedded in physical nature (and not outside nature, as frequently assumed in western culture).

  3. What The Cognitive Neurosciences Mean To Me

    PubMed Central

    Pereira, Alfredo

    2007-01-01

    Cognitive Neuroscience is an interdisciplinary area of research that combines measurement of brain activity (mostly by means of neuroimaging) with a simultaneous performance of cognitive tasks by human subjects. These investigations have been successful in the task of connecting the sciences of the brain (Neurosciences) and the sciences of the mind (Cognitive Sciences). Advances on this kind of research provide a map of localization of cognitive functions in the human brain. Do these results help us to understand how mind relates to the brain? In my view, the results obtained by the Cognitive Neurosciences lead to new investigations in the domain of Molecular Neurobiology, aimed at discovering biophysical mechanisms that generate the activity measured by neuroimaging instruments. In this context, I argue that the understanding of how ionic/molecular processes support cognition and consciousness cannot be made by means of the standard reductionist explanations. Knowledge of ionic/molecular mechanisms can contribute to our understanding of the human mind as long as we assume an alternative form of explanation, based on psycho-physical similarities, together with an ontological view of mentality and spirituality as embedded in physical nature (and not outside nature, as frequently assumed in western culture). PMID:22058629

  4. Construction of multi-scale consistent brain networks: methods and applications.

    PubMed

    Ge, Bao; Tian, Yin; Hu, Xintao; Chen, Hanbo; Zhu, Dajiang; Zhang, Tuo; Han, Junwei; Guo, Lei; Liu, Tianming

    2015-01-01

    Mapping human brain networks provides a basis for studying brain function and dysfunction, and thus has gained significant interest in recent years. However, modeling human brain networks still faces several challenges including constructing networks at multiple spatial scales and finding common corresponding networks across individuals. As a consequence, many previous methods were designed for a single resolution or scale of brain network, though the brain networks are multi-scale in nature. To address this problem, this paper presents a novel approach to constructing multi-scale common structural brain networks from DTI data via an improved multi-scale spectral clustering applied on our recently developed and validated DICCCOLs (Dense Individualized and Common Connectivity-based Cortical Landmarks). Since the DICCCOL landmarks possess intrinsic structural correspondences across individuals and populations, we employed the multi-scale spectral clustering algorithm to group the DICCCOL landmarks and their connections into sub-networks, meanwhile preserving the intrinsically-established correspondences across multiple scales. Experimental results demonstrated that the proposed method can generate multi-scale consistent and common structural brain networks across subjects, and its reproducibility has been verified by multiple independent datasets. As an application, these multi-scale networks were used to guide the clustering of multi-scale fiber bundles and to compare the fiber integrity in schizophrenia and healthy controls. In general, our methods offer a novel and effective framework for brain network modeling and tract-based analysis of DTI data.

  5. A 2.5-D Representation of the Human Hand

    ERIC Educational Resources Information Center

    Longo, Matthew R.; Haggard, Patrick

    2012-01-01

    Primary somatosensory maps in the brain represent the body as a discontinuous, fragmented set of two-dimensional (2-D) skin regions. We nevertheless experience our body as a coherent three-dimensional (3-D) volumetric object. The links between these different aspects of body representation, however, remain poorly understood. Perceiving the body's…

  6. The BRAIN Initiative: developing technology to catalyse neuroscience discovery.

    PubMed

    Jorgenson, Lyric A; Newsome, William T; Anderson, David J; Bargmann, Cornelia I; Brown, Emery N; Deisseroth, Karl; Donoghue, John P; Hudson, Kathy L; Ling, Geoffrey S F; MacLeish, Peter R; Marder, Eve; Normann, Richard A; Sanes, Joshua R; Schnitzer, Mark J; Sejnowski, Terrence J; Tank, David W; Tsien, Roger Y; Ugurbil, Kamil; Wingfield, John C

    2015-05-19

    The evolution of the field of neuroscience has been propelled by the advent of novel technological capabilities, and the pace at which these capabilities are being developed has accelerated dramatically in the past decade. Capitalizing on this momentum, the United States launched the Brain Research through Advancing Innovative Neurotechnologies (BRAIN) Initiative to develop and apply new tools and technologies for revolutionizing our understanding of the brain. In this article, we review the scientific vision for this initiative set forth by the National Institutes of Health and discuss its implications for the future of neuroscience research. Particular emphasis is given to its potential impact on the mapping and study of neural circuits, and how this knowledge will transform our understanding of the complexity of the human brain and its diverse array of behaviours, perceptions, thoughts and emotions.

  7. Hierarchical functional modularity in the resting-state human brain.

    PubMed

    Ferrarini, Luca; Veer, Ilya M; Baerends, Evelinda; van Tol, Marie-José; Renken, Remco J; van der Wee, Nic J A; Veltman, Dirk J; Aleman, André; Zitman, Frans G; Penninx, Brenda W J H; van Buchem, Mark A; Reiber, Johan H C; Rombouts, Serge A R B; Milles, Julien

    2009-07-01

    Functional magnetic resonance imaging (fMRI) studies have shown that anatomically distinct brain regions are functionally connected during the resting state. Basic topological properties in the brain functional connectivity (BFC) map have highlighted the BFC's small-world topology. Modularity, a more advanced topological property, has been hypothesized to be evolutionary advantageous, contributing to adaptive aspects of anatomical and functional brain connectivity. However, current definitions of modularity for complex networks focus on nonoverlapping clusters, and are seriously limited by disregarding inclusive relationships. Therefore, BFC's modularity has been mainly qualitatively investigated. Here, we introduce a new definition of modularity, based on a recently improved clustering measurement, which overcomes limitations of previous definitions, and apply it to the study of BFC in resting state fMRI of 53 healthy subjects. Results show hierarchical functional modularity in the brain. Copyright 2009 Wiley-Liss, Inc

  8. The BRAIN Initiative: developing technology to catalyse neuroscience discovery

    PubMed Central

    Jorgenson, Lyric A.; Newsome, William T.; Anderson, David J.; Bargmann, Cornelia I.; Brown, Emery N.; Deisseroth, Karl; Donoghue, John P.; Hudson, Kathy L.; Ling, Geoffrey S. F.; MacLeish, Peter R.; Marder, Eve; Normann, Richard A.; Sanes, Joshua R.; Schnitzer, Mark J.; Sejnowski, Terrence J.; Tank, David W.; Tsien, Roger Y.; Ugurbil, Kamil; Wingfield, John C.

    2015-01-01

    The evolution of the field of neuroscience has been propelled by the advent of novel technological capabilities, and the pace at which these capabilities are being developed has accelerated dramatically in the past decade. Capitalizing on this momentum, the United States launched the Brain Research through Advancing Innovative Neurotechnologies (BRAIN) Initiative to develop and apply new tools and technologies for revolutionizing our understanding of the brain. In this article, we review the scientific vision for this initiative set forth by the National Institutes of Health and discuss its implications for the future of neuroscience research. Particular emphasis is given to its potential impact on the mapping and study of neural circuits, and how this knowledge will transform our understanding of the complexity of the human brain and its diverse array of behaviours, perceptions, thoughts and emotions. PMID:25823863

  9. Focused ultrasound delivery of Raman nanoparticles across the blood-brain barrier: potential for targeting experimental brain tumors.

    PubMed

    Diaz, Roberto Jose; McVeigh, Patrick Z; O'Reilly, Meaghan A; Burrell, Kelly; Bebenek, Matthew; Smith, Christian; Etame, Arnold B; Zadeh, Gelareh; Hynynen, Kullervo; Wilson, Brian C; Rutka, James T

    2014-07-01

    Spectral mapping of nanoparticles with surface enhanced Raman scattering (SERS) capability in the near-infrared range is an emerging molecular imaging technique. We used magnetic resonance image-guided transcranial focused ultrasound (TcMRgFUS) to reversibly disrupt the blood-brain barrier (BBB) adjacent to brain tumor margins in rats. Glioma cells were found to internalize SERS capable nanoparticles of 50nm or 120nm physical diameter. Surface coating with anti-epidermal growth factor receptor antibody or non-specific human immunoglobulin G, resulted in enhanced cell uptake of nanoparticles in-vitro compared to nanoparticles with methyl terminated 12-unit polyethylene glycol surface. BBB disruption permitted the delivery of SERS capable spherical 50 or 120nm gold nanoparticles to the tumor margins. Thus, nanoparticles with SERS imaging capability can be delivered across the BBB non-invasively using TcMRgFUS and have the potential to be used as optical tracking agents at the invasive front of malignant brain tumors. This study demonstrates the use of magnetic resonance image-guided transcranial focused ultrasound to open the BBB and enable spectral mapping of nanoparticles with surface enhanced Raman scattering (SERS)-based molecular imaging for experimental tumor tracking. Copyright © 2014 Elsevier Inc. All rights reserved.

  10. Spatiotemporal patterns of ERP based on combined ICA-LORETA analysis

    NASA Astrophysics Data System (ADS)

    Zhang, Jiacai; Guo, Taomei; Xu, Yaqin; Zhao, Xiaojie; Yao, Li

    2007-03-01

    In contrast to the FMRI methods widely used up to now, this method try to understand more profoundly how the brain systems work under sentence processing task map accurately the spatiotemporal patterns of activity of the large neuronal populations in the human brain from the analysis of ERP data recorded on the brain scalp. In this study, an event-related brain potential (ERP) paradigm to record the on-line responses to the processing of sentences is chosen as an example. In order to give attention to both utilizing the ERPs' temporal resolution of milliseconds and overcoming the insensibility of cerebral location ERP sources, we separate these sources in space and time based on a combined method of independent component analysis (ICA) and low-resolution tomography (LORETA) algorithms. ICA blindly separate the input ERP data into a sum of temporally independent and spatially fixed components arising from distinct or overlapping brain or extra-brain sources. And then the spatial maps associated with each ICA component are analyzed, with use of LORETA to uniquely locate its cerebral sources throughout the full brain according to the assumption that neighboring neurons are simultaneously and synchronously activated. Our results show that the cerebral computation mechanism underlies content words reading is mediated by the orchestrated activity of several spatially distributed brain sources located in the temporal, frontal, and parietal areas, and activate at distinct time intervals and are grouped into different statistically independent components. Thus ICA-LORETA analysis provides an encouraging and effective method to study brain dynamics from ERP.

  11. Resting state cerebral blood flow with arterial spin labeling MRI in developing human brains.

    PubMed

    Liu, Feng; Duan, Yunsuo; Peterson, Bradley S; Asllani, Iris; Zelaya, Fernando; Lythgoe, David; Kangarlu, Alayar

    2018-07-01

    The development of brain circuits is coupled with changes in neurovascular coupling, which refers to the close relationship between neural activity and cerebral blood flow (CBF). Studying the characteristics of CBF during resting state in developing brain can be a complementary way to understand the functional connectivity of the developing brain. Arterial spin labeling (ASL), as a noninvasive MR technique, is particularly attractive for studying cerebral perfusion in children and even newborns. We have collected pulsed ASL data in resting state for 47 healthy subjects from young children to adolescence (aged from 6 to 20 years old). In addition to studying the developmental change of static CBF maps during resting state, we also analyzed the CBF time series to reveal the dynamic characteristics of CBF in differing age groups. We used the seed-based correlation analysis to examine the temporal relationship of CBF time series between the selected ROIs and other brain regions. We have shown the developmental patterns in both static CBF maps and dynamic characteristics of CBF. While higher CBF of default mode network (DMN) in all age groups supports that DMN is the prominent active network during the resting state, the CBF connectivity patterns of some typical resting state networks show distinct patterns of metabolic activity during the resting state in the developing brains. Copyright © 2018 European Paediatric Neurology Society. All rights reserved.

  12. The Structural Connectome of the Human Central Homeostatic Network.

    PubMed

    Edlow, Brian L; McNab, Jennifer A; Witzel, Thomas; Kinney, Hannah C

    2016-04-01

    Homeostatic adaptations to stress are regulated by interactions between the brainstem and regions of the forebrain, including limbic sites related to respiratory, autonomic, affective, and cognitive processing. Neuroanatomic connections between these homeostatic regions, however, have not been thoroughly identified in the human brain. In this study, we perform diffusion spectrum imaging tractography using the MGH-USC Connectome MRI scanner to visualize structural connections in the human brain linking autonomic and cardiorespiratory nuclei in the midbrain, pons, and medulla oblongata with forebrain sites critical to homeostatic control. Probabilistic tractography analyses in six healthy adults revealed connections between six brainstem nuclei and seven forebrain regions, several over long distances between the caudal medulla and cerebral cortex. The strongest evidence for brainstem-homeostatic forebrain connectivity in this study was between the brainstem midline raphe and the medial temporal lobe. The subiculum and amygdala were the sampled forebrain nodes with the most extensive brainstem connections. Within the human brainstem-homeostatic forebrain connectome, we observed that a lateral forebrain bundle, whose connectivity is distinct from that of rodents and nonhuman primates, is the primary conduit for connections between the brainstem and medial temporal lobe. This study supports the concept that interconnected brainstem and forebrain nodes form an integrated central homeostatic network (CHN) in the human brain. Our findings provide an initial foundation for elucidating the neuroanatomic basis of homeostasis in the normal human brain, as well as for mapping CHN disconnections in patients with disorders of homeostasis, including sudden and unexpected death, and epilepsy.

  13. No-carrier-added (18F)-N-methylspiroperidol

    DOEpatents

    Shiue, Chyng-Yann; Fowler, Joanna S.; Wolf, Alfred P.

    1993-01-01

    There is disclosed a radioligand labeled with a positron emitting radionuclide suitable for dynamic study in living humans with positron emission transaxial tomography. [.sup.18 F]-N-methylspiroperidol, exhibiting extremely high affinity for the dopamine receptors, provides enhanced uptake and retention in the brain concomitant with reduced radiation burden. These characteristics all combine to provide [.sup.18 F]-N-methylspiroperidol as a radioligand superior to known radioligands for mapping dopamine receptors in normal and disease states in the living brain. Additionally, a new synthetic procedure for this material is disclosed.

  14. No-carrier-added (18F)-N-methylspiroperidol

    DOEpatents

    Shiue, Chyng-Yann; Fowler, Joanna S.; Wolf, Alfred P.

    1993-07-06

    There is disclosed a radioligand labeled with a positron emitting radionuclide suitable for dynamic study in living humans with positron emission transaxial tomography. [.sup.18 F]-N-methylspiroperidol, exhibiting extremely high affinity for the dopamine receptors, provides enhanced uptake and retention in the brain concomitant with reduced radiation burden. These characteristics all combine to provide [.sup.18 F]-N-methylspiroperidol as a radioligand superior to known radioligands for mapping dopamine receptors in normal and disease states in the living brain. Additionally, a new synthetic procedure for this material is disclosed.

  15. Brain dynamics of post-task resting state are influenced by expertise: Insights from baseball players.

    PubMed

    Muraskin, Jordan; Dodhia, Sonam; Lieberman, Gregory; Garcia, Javier O; Verstynen, Timothy; Vettel, Jean M; Sherwin, Jason; Sajda, Paul

    2016-12-01

    Post-task resting state dynamics can be viewed as a task-driven state where behavioral performance is improved through endogenous, non-explicit learning. Tasks that have intrinsic value for individuals are hypothesized to produce post-task resting state dynamics that promote learning. We measured simultaneous fMRI/EEG and DTI in Division-1 collegiate baseball players and compared to a group of controls, examining differences in both functional and structural connectivity. Participants performed a surrogate baseball pitch Go/No-Go task before a resting state scan, and we compared post-task resting state connectivity using a seed-based analysis from the supplementary motor area (SMA), an area whose activity discriminated players and controls in our previous results using this task. Although both groups were equally trained on the task, the experts showed differential activity in their post-task resting state consistent with motor learning. Specifically, we found (1) differences in bilateral SMA-L Insula functional connectivity between experts and controls that may reflect group differences in motor learning, (2) differences in BOLD-alpha oscillation correlations between groups suggests variability in modulatory attention in the post-task state, and (3) group differences between BOLD-beta oscillations that may indicate cognitive processing of motor inhibition. Structural connectivity analysis identified group differences in portions of the functionally derived network, suggesting that functional differences may also partially arise from variability in the underlying white matter pathways. Generally, we find that brain dynamics in the post-task resting state differ as a function of subject expertise and potentially result from differences in both functional and structural connectivity. Hum Brain Mapp 37:4454-4471, 2016. © 2016 The Authors Human Brain Mapping Published by Wiley Periodicals, Inc. © 2016 The Authors Human Brain Mapping Published by Wiley Periodicals, Inc.

  16. Functional connectivity and information flow of the respiratory neural network in chronic obstructive pulmonary disease.

    PubMed

    Yu, Lianchun; De Mazancourt, Marine; Hess, Agathe; Ashadi, Fakhrul R; Klein, Isabelle; Mal, Hervé; Courbage, Maurice; Mangin, Laurence

    2016-08-01

    Breathing involves a complex interplay between the brainstem automatic network and cortical voluntary command. How these brain regions communicate at rest or during inspiratory loading is unknown. This issue is crucial for several reasons: (i) increased respiratory loading is a major feature of several respiratory diseases, (ii) failure of the voluntary motor and cortical sensory processing drives is among the mechanisms that precede acute respiratory failure, (iii) several cerebral structures involved in responding to inspiratory loading participate in the perception of dyspnea, a distressing symptom in many disease. We studied functional connectivity and Granger causality of the respiratory network in controls and patients with chronic obstructive pulmonary disease (COPD), at rest and during inspiratory loading. Compared with those of controls, the motor cortex area of patients exhibited decreased connectivity with their contralateral counterparts and no connectivity with the brainstem. In the patients, the information flow was reversed at rest with the source of the network shifted from the medulla towards the motor cortex. During inspiratory loading, the system was overwhelmed and the motor cortex became the sink of the network. This major finding may help to understand why some patients with COPD are prone to acute respiratory failure. Network connectivity and causality were related to lung function and illness severity. We validated our connectivity and causality results with a mathematical model of neural network. Our findings suggest a new therapeutic strategy involving the modulation of brain activity to increase motor cortex functional connectivity and improve respiratory muscles performance in patients. Hum Brain Mapp 37:2736-2754, 2016. © 2016 The Authors Human Brain Mapping Published by Wiley Periodicals, Inc. © 2016 The Authors Human Brain Mapping Published by Wiley Periodicals, Inc.

  17. Limbic grey matter changes in early Parkinson's disease.

    PubMed

    Li, Xingfeng; Xing, Yue; Schwarz, Stefan T; Auer, Dorothee P

    2017-05-02

    The purpose of this study was to investigate local and network-related changes of limbic grey matter in early Parkinson's disease (PD) and their inter-relation with non-motor symptom severity. We applied voxel-based morphometric methods in 538 T1 MRI images retrieved from the Parkinson's Progression Markers Initiative website. Grey matter densities and cross-sectional estimates of age-related grey matter change were compared between subjects with early PD (n = 366) and age-matched healthy controls (n = 172) within a regression model, and associations of grey matter density with symptoms were investigated. Structural brain networks were obtained using covariance analysis seeded in regions showing grey matter abnormalities in PD subject group. Patients displayed focally reduced grey matter density in the right amygdala, which was present from the earliest stages of the disease without further advance in mild-moderate disease stages. Right amygdala grey matter density showed negative correlation with autonomic dysfunction and positive with cognitive performance in patients, but no significant interrelations were found with anxiety scores. Patients with PD also demonstrated right amygdala structural disconnection with less structural connectivity of the right amygdala with the cerebellum and thalamus but increased covariance with bilateral temporal cortices compared with controls. Age-related grey matter change was also increased in PD preferentially in the limbic system. In conclusion, detailed brain morphometry in a large group of early PD highlights predominant limbic grey matter deficits with stronger age associations compared with controls and associated altered structural connectivity pattern. This provides in vivo evidence for early limbic grey matter pathology and structural network changes that may reflect extranigral disease spread in PD. Hum Brain Mapp, 2017. © 2017 The Authors Human Brain Mapping Published by Wiley Periodicals, Inc. © 2017 The Authors Human Brain Mapping Published by Wiley Periodicals, Inc.

  18. Iron biomineralization of brain tissue and neurodegenerative disorders

    NASA Astrophysics Data System (ADS)

    Mikhaylova (Mikhailova), Albina

    The brain is an organ with a high concentration of iron in specific areas, particularly in the globus pallidus, the substantia nigra, and the red nucleus. In certain pathological states, such as iron overload disease and neurodegenerative disorders, a disturbed iron metabolism can lead to increased accumulation of iron not only in these areas, but also in the brain regions that are typically low in iron content. Recent studies of the physical and magnetic properties of metalloproteins, and in particular the discovery of biogenic magnetite in human brain tissue, have raised new questions about the role of biogenic iron formations in living organisms. Further investigations revealed the presence of magnetite-like crystalline structures in human ferritin, and indicated that released ferritin iron might act as promoter of oxidative damage to tissue, therefore contributing to pathogenesis of neurodegenerative disorders such as Alzheimer's, Parkinson's and Huntington's diseases. The purpose of this work was to examine the elemental composition and structure of iron deposits in normal brain tissue as well as tissue affected by neurodegenerative disorders. Employing the methods of X-ray microfocus fluorescence mapping, X-ray Absorption Near Edge Structure (XANES), X-ray Absorption Fine Structure spectroscopy (XAFS), and light and electron microscopic examinations allows one to obtain qualitative as well as quantitative data with respect to the cellular distribution and chemical state of iron at levels not detected previously. The described tissue preparation technique allows not only satisfactory XAS iron elemental imaging in situ but also multimodal examination with light and electron microscopes of the same samples. The developed protocol has assured consistent and reproducible results on relatively large sections of flat-embedded tissue. The resulting tissue samples were adequate for XAS examination as well as sufficiently well-preserved for future microscopy studies. The continued development of this technique should lead to major advances in mapping iron anomalies and the related chemical and structural information directly to cells and tissue structures in human brain tissue. At present this is done primarily by iron staining methods and any information on the relationship between iron distribution and cellular structures obtained this way is limited. Iron staining also offers no information on the specific compounds of iron that are present. This can be vitally important as the form of iron [including its oxidation state] in the human body can determine whether it plays a detrimental or beneficial role in neurophysiological processes.

  19. 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

  20. Minocycline Effects on Intracerebral Hemorrhage-Induced Iron Overload in Aged Rats: Brain Iron Quantification With Magnetic Resonance Imaging.

    PubMed

    Cao, Shenglong; Hua, Ya; Keep, Richard F; Chaudhary, Neeraj; Xi, Guohua

    2018-04-01

    Brain iron overload is a key factor causing brain injury after intracerebral hemorrhage (ICH). This study quantified brain iron levels after ICH with magnetic resonance imaging R2* mapping. The effect of minocycline on iron overload and ICH-induced brain injury in aged rats was also determined. Aged (18 months old) male Fischer 344 rats had an intracerebral injection of autologous blood or saline, and brain iron levels were measured by magnetic resonance imaging R2* mapping. Some ICH rats were treated with minocycline or vehicle. The rats were euthanized at days 7 and 28 after ICH, and brains were used for immunohistochemistry and Western blot analyses. Magnetic resonance imaging (T2-weighted, T2* gradient-echo, and R2* mapping) sequences were performed at different time points. ICH-induced brain iron overload in the perihematomal area could be quantified by R2* mapping. Minocycline treatment reduced brain iron accumulation, T2* lesion volume, iron-handling protein upregulation, neuronal cell death, and neurological deficits ( P <0.05). Magnetic resonance imaging R2* mapping is a reliable and noninvasive method, which can quantitatively measure brain iron levels after ICH. Minocycline reduced ICH-related perihematomal iron accumulation and brain injury in aged rats. © 2018 American Heart Association, Inc.

  1. Autoradiographic distribution of 5-HT7 receptors in the human brain using [3H]mesulergine: comparison to other mammalian species

    PubMed Central

    Martín-Cora, Francisco J; Pazos, Angel

    2003-01-01

    The main aim of this investigation was to delineate the distribution of the 5-HT7 receptor in human brain. Autoradiographic studies in guinea-pig and rat brain were also carried out in order to revisit and compare the anatomical distribution of 5-HT7 receptors in different mammalian species.Binding studies were performed in rat frontal cortex membranes using 10 nM [3H]mesulergine in the presence of raclopride (10 μM) and DOI (0.8 μM). Under these conditions, a binding site with pharmacological characteristics consistent with those of the 5-HT7 receptors was identified (rank order of binding affinity values: 5-CT>5-HT>5-MeOT>mesulergine ≈methiothepin>8-OH-DPAT=spiperone ≈(+)-butaclamol≫imipramine ≈(±)-pindolol≫ondansetron ≈clonidine ≈prazosin).The autoradiographic studies revealed that the anatomical distribution of 5-HT7 receptors throughout the human brain was heterogenous. High densities were found over the caudate and putamen nuclei, the pyramidal layer of the CA2 field of the hippocampus, the centromedial thalamic nucleus, and the dorsal raphe nucleus. The inner layer of the frontal cortex, the dentate gyrus of the hippocampus, the subthalamic nucleus and superior colliculus, among others, presented intermediate concentrations of 5-HT7 receptors. A similar brain anatomical distribution of 5-HT7 receptors was observed in all three mammalian species studied.By using [3H]mesulergine, we have mapped for the first time the anatomical distribution of 5-HT7 receptors in the human brain, overcoming the limitations previously found in radiometric studies with other radioligands, and also revisiting the distribution in guinea-pig and rat brain. PMID:14656806

  2. 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.

  3. Mapping brain development during childhood, adolescence and young adulthood

    NASA Astrophysics Data System (ADS)

    Guo, Xiaojuan; Jin, Zhen; Chen, Kewei; Peng, Danling; Li, Yao

    2009-02-01

    Using optimized voxel-based morphometry (VBM), this study systematically investigated the differences and similarities of brain structural changes during the early three developmental periods of human lives: childhood, adolescence and young adulthood. These brain changes were discussed in relationship to the corresponding cognitive function development during these three periods. Magnetic Resonance Imaging (MRI) data from 158 Chinese healthy children, adolescents and young adults, aged 7.26 to 22.80 years old, were included in this study. Using the customized brain template together with the gray matter/white matter/cerebrospinal fluid prior probability maps, we found that there were more age-related positive changes in the frontal lobe, less in hippocampus and amygdala during childhood, but more in bilateral hippocampus and amygdala and left fusiform gyrus during adolescence and young adulthood. There were more age-related negative changes near to central sulcus during childhood, but these changes extended to the frontal and parietal lobes, mainly in the parietal lobe, during adolescence and young adulthood, and more in the prefrontal lobe during young adulthood. So gray matter volume in the parietal lobe significantly decreased from childhood and continued to decrease till young adulthood. These findings may aid in understanding the age-related differences in cognitive function.

  4. Interpretability of Multivariate Brain Maps in Linear Brain Decoding: Definition, and Heuristic Quantification in Multivariate Analysis of MEG Time-Locked Effects.

    PubMed

    Kia, Seyed Mostafa; Vega Pons, Sandro; Weisz, Nathan; Passerini, Andrea

    2016-01-01

    Brain decoding is a popular multivariate approach for hypothesis testing in neuroimaging. Linear classifiers are widely employed in the brain decoding paradigm to discriminate among experimental conditions. Then, the derived linear weights are visualized in the form of multivariate brain maps to further study spatio-temporal patterns of underlying neural activities. It is well known that the brain maps derived from weights of linear classifiers are hard to interpret because of high correlations between predictors, low signal to noise ratios, and the high dimensionality of neuroimaging data. Therefore, improving the interpretability of brain decoding approaches is of primary interest in many neuroimaging studies. Despite extensive studies of this type, at present, there is no formal definition for interpretability of multivariate brain maps. As a consequence, there is no quantitative measure for evaluating the interpretability of different brain decoding methods. In this paper, first, we present a theoretical definition of interpretability in brain decoding; we show that the interpretability of multivariate brain maps can be decomposed into their reproducibility and representativeness. Second, as an application of the proposed definition, we exemplify a heuristic for approximating the interpretability in multivariate analysis of evoked magnetoencephalography (MEG) responses. Third, we propose to combine the approximated interpretability and the generalization performance of the brain decoding into a new multi-objective criterion for model selection. Our results, for the simulated and real MEG data, show that optimizing the hyper-parameters of the regularized linear classifier based on the proposed criterion results in more informative multivariate brain maps. More importantly, the presented definition provides the theoretical background for quantitative evaluation of interpretability, and hence, facilitates the development of more effective brain decoding algorithms in the future.

  5. Interpretability of Multivariate Brain Maps in Linear Brain Decoding: Definition, and Heuristic Quantification in Multivariate Analysis of MEG Time-Locked Effects

    PubMed Central

    Kia, Seyed Mostafa; Vega Pons, Sandro; Weisz, Nathan; Passerini, Andrea

    2017-01-01

    Brain decoding is a popular multivariate approach for hypothesis testing in neuroimaging. Linear classifiers are widely employed in the brain decoding paradigm to discriminate among experimental conditions. Then, the derived linear weights are visualized in the form of multivariate brain maps to further study spatio-temporal patterns of underlying neural activities. It is well known that the brain maps derived from weights of linear classifiers are hard to interpret because of high correlations between predictors, low signal to noise ratios, and the high dimensionality of neuroimaging data. Therefore, improving the interpretability of brain decoding approaches is of primary interest in many neuroimaging studies. Despite extensive studies of this type, at present, there is no formal definition for interpretability of multivariate brain maps. As a consequence, there is no quantitative measure for evaluating the interpretability of different brain decoding methods. In this paper, first, we present a theoretical definition of interpretability in brain decoding; we show that the interpretability of multivariate brain maps can be decomposed into their reproducibility and representativeness. Second, as an application of the proposed definition, we exemplify a heuristic for approximating the interpretability in multivariate analysis of evoked magnetoencephalography (MEG) responses. Third, we propose to combine the approximated interpretability and the generalization performance of the brain decoding into a new multi-objective criterion for model selection. Our results, for the simulated and real MEG data, show that optimizing the hyper-parameters of the regularized linear classifier based on the proposed criterion results in more informative multivariate brain maps. More importantly, the presented definition provides the theoretical background for quantitative evaluation of interpretability, and hence, facilitates the development of more effective brain decoding algorithms in the future. PMID:28167896

  6. Compressed sensing for high-resolution nonlipid suppressed 1 H FID MRSI of the human brain at 9.4T.

    PubMed

    Nassirpour, Sahar; Chang, Paul; Avdievitch, Nikolai; Henning, Anke

    2018-04-29

    The aim of this study was to apply compressed sensing to accelerate the acquisition of high resolution metabolite maps of the human brain using a nonlipid suppressed ultra-short TR and TE 1 H FID MRSI sequence at 9.4T. X-t sparse compressed sensing reconstruction was optimized for nonlipid suppressed 1 H FID MRSI data. Coil-by-coil x-t sparse reconstruction was compared with SENSE x-t sparse and low rank reconstruction. The effect of matrix size and spatial resolution on the achievable acceleration factor was studied. Finally, in vivo metabolite maps with different acceleration factors of 2, 4, 5, and 10 were acquired and compared. Coil-by-coil x-t sparse compressed sensing reconstruction was not able to reliably recover the nonlipid suppressed data, rather a combination of parallel and sparse reconstruction was necessary (SENSE x-t sparse). For acceleration factors of up to 5, both the low-rank and the compressed sensing methods were able to reconstruct the data comparably well (root mean squared errors [RMSEs] ≤ 10.5% for Cre). However, the reconstruction time of the low rank algorithm was drastically longer than compressed sensing. Using the optimized compressed sensing reconstruction, acceleration factors of 4 or 5 could be reached for the MRSI data with a matrix size of 64 × 64. For lower spatial resolutions, an acceleration factor of up to R∼4 was successfully achieved. By tailoring the reconstruction scheme to the nonlipid suppressed data through parameter optimization and performance evaluation, we present high resolution (97 µL voxel size) accelerated in vivo metabolite maps of the human brain acquired at 9.4T within scan times of 3 to 3.75 min. © 2018 International Society for Magnetic Resonance in Medicine.

  7. Morphometric analysis and neuroanatomical mapping of the zebrafish brain.

    PubMed

    Gupta, Tripti; Marquart, Gregory D; Horstick, Eric J; Tabor, Kathryn M; Pajevic, Sinisa; Burgess, Harold A

    2018-06-21

    Large-scale genomic studies have recently identified genetic variants causative for major neurodevelopmental disorders, such as intellectual disability and autism. However, determining how underlying developmental processes are affected by these mutations remains a significant challenge in the field. Zebrafish is an established model system in developmental neurogenetics that may be useful in uncovering the mechanisms of these mutations. Here we describe the use of voxel-intensity, deformation field, and volume-based morphometric techniques for the systematic and unbiased analysis of gene knock-down and environmental exposure-induced phenotypes in zebrafish. We first present a computational method for brain segmentation based on transgene expression patterns to create a comprehensive neuroanatomical map. This map allowed us to disclose statistically significant changes in brain microstructure and composition in neurodevelopmental models. We demonstrate the effectiveness of morphometric techniques in measuring changes in the relative size of neuroanatomical subdivisions in atoh7 morphant larvae and in identifying phenotypes in larvae treated with valproic acid, a chemical demonstrated to increase the risk of autism in humans. These tools enable rigorous evaluation of the effects of gene mutations and environmental exposures on neural development, providing an entry point for cellular and molecular analysis of basic developmental processes as well as neurodevelopmental and neurodegenerative disorders. Published by Elsevier Inc.

  8. Topographic Brain Mapping: A Window on Brain Function?

    ERIC Educational Resources Information Center

    Karniski, Walt M.

    1989-01-01

    The article reviews the method of topographic mapping of the brain's electrical activity. Multiple electroencephalogram (EEG) electrodes and computerized analysis of the EEG signal are used to generate maps of frequency and voltage (evoked potential). This relatively new technique holds promise in the evaluation of children with behavioral and…

  9. New whole-body sensory-motor gradients revealed using phase-locked analysis and verified using multivoxel pattern analysis and functional connectivity.

    PubMed

    Zeharia, Noa; Hertz, Uri; Flash, Tamar; Amedi, Amir

    2015-02-18

    Topographic organization is one of the main principles of organization in the human brain. Specifically, whole-brain topographic mapping using spectral analysis is responsible for one of the greatest advances in vision research. Thus, it is intriguing that although topography is a key feature also in the motor system, whole-body somatosensory-motor mapping using spectral analysis has not been conducted in humans outside M1/SMA. Here, using this method, we were able to map a homunculus in the globus pallidus, a key target area for deep brain stimulation, which has not been mapped noninvasively or in healthy subjects. The analysis clarifies contradictory and partial results regarding somatotopy in the caudal-cingulate zone and rostral-cingulate zone in the medial wall and in the putamen. Most of the results were confirmed at the single-subject level and were found to be compatible with results from animal studies. Using multivoxel pattern analysis, we could predict movements of individual body parts in these homunculi, thus confirming that they contain somatotopic information. Using functional connectivity, we demonstrate interhemispheric functional somatotopic connectivity of these homunculi, such that the somatotopy in one hemisphere could have been found given the connectivity pattern of the corresponding regions of interest in the other hemisphere. When inspecting the somatotopic and nonsomatotopic connectivity patterns, a similarity index indicated that the pattern of connected and nonconnected regions of interest across different homunculi is similar for different body parts and hemispheres. The results show that topographical gradients are even more widespread than previously assumed in the somatosensory-motor system. Spectral analysis can thus potentially serve as a gold standard for defining somatosensory-motor system areas for basic research and clinical applications. Copyright © 2015 the authors 0270-6474/15/352845-15$15.00/0.

  10. A Mathematical Model for Storage and Recall of Images using Targeted Synchronization of Coupled Maps.

    PubMed

    Palaniyandi, P; Rangarajan, Govindan

    2017-08-21

    We propose a mathematical model for storage and recall of images using coupled maps. We start by theoretically investigating targeted synchronization in coupled map systems wherein only a desired (partial) subset of the maps is made to synchronize. A simple method is introduced to specify coupling coefficients such that targeted synchronization is ensured. The principle of this method is extended to storage/recall of images using coupled Rulkov maps. The process of adjusting coupling coefficients between Rulkov maps (often used to model neurons) for the purpose of storing a desired image mimics the process of adjusting synaptic strengths between neurons to store memories. Our method uses both synchronisation and synaptic weight modification, as the human brain is thought to do. The stored image can be recalled by providing an initial random pattern to the dynamical system. The storage and recall of the standard image of Lena is explicitly demonstrated.

  11. Cerebrovascular-Reactivity Mapping Using MRI: Considerations for Alzheimer's Disease.

    PubMed

    Chen, J J

    2018-01-01

    Alzheimer's disease (AD) is associated with well-established macrostructural and cellular markers, including localized brain atrophy and deposition of amyloid. However, there is growing recognition of the link between cerebrovascular dysfunction and AD, supported by continuous experimental evidence in the animal and human literature. As a result, neuroimaging studies of AD are increasingly aiming to incorporate vascular measures, exemplified by measures of cerebrovascular reactivity (CVR). CVR is a measure that is rooted in clinical practice, and as non-invasive CVR-mapping techniques become more widely available, routine CVR mapping may open up new avenues of investigation into the development of AD. This review focuses on the use of MRI to map CVR, paying specific attention to recent developments in MRI methodology and on the emerging stimulus-free approaches to CVR mapping. It also summarizes the biological basis for the vascular contribution to AD, and provides critical perspective on the choice of CVR-mapping techniques amongst frail populations.

  12. Robust biological parametric mapping: an improved technique for multimodal brain image analysis

    NASA Astrophysics Data System (ADS)

    Yang, Xue; Beason-Held, Lori; Resnick, Susan M.; Landman, Bennett A.

    2011-03-01

    Mapping the quantitative relationship between structure and function in the human brain is an important and challenging problem. Numerous volumetric, surface, region of interest and voxelwise image processing techniques have been developed to statistically assess potential correlations between imaging and non-imaging metrics. Recently, biological parametric mapping has extended the widely popular statistical parametric approach to enable application of the general linear model to multiple image modalities (both for regressors and regressands) along with scalar valued observations. This approach offers great promise for direct, voxelwise assessment of structural and functional relationships with multiple imaging modalities. However, as presented, the biological parametric mapping approach is not robust to outliers and may lead to invalid inferences (e.g., artifactual low p-values) due to slight mis-registration or variation in anatomy between subjects. To enable widespread application of this approach, we introduce robust regression and robust inference in the neuroimaging context of application of the general linear model. Through simulation and empirical studies, we demonstrate that our robust approach reduces sensitivity to outliers without substantial degradation in power. The robust approach and associated software package provides a reliable way to quantitatively assess voxelwise correlations between structural and functional neuroimaging modalities.

  13. Sewer pipe, wire, epoxy, and finger tapping: The start of fMRI at the Medical College of Wisconsin

    PubMed Central

    Bandettini, Peter A.

    2011-01-01

    In 1991, the Biophysics Research Institute at the Medical College of Wisconsin was among the first groups to develop functional Magnetic Resonance Imaging (fMRI). Our story is unique on a few levels: We didn’t have knowledge of the ability to image human brain activation with MRI using blood oxygenation dependent (BOLD) contrast until early August of 1991 when we attended the Society for Magnetic Resonance in Medicine (SMRM) meeting in San Francisco, yet we produced our first BOLD-based maps of motor cortex activation about a month later. The effort started with two graduate students, Eric Wong and myself. Only a few days prior to that extremely important SMRM meeting, we had developed human echo planar imaging (EPI) capability in-house. Wong designed, built, and interfaced a head gradient coil made out of sewer pipe, wire, and epoxy to a standard GE 1.5 T MRI scanner. Also, a few months prior to building this human head gradient coil he developed the EPI pulse sequences and image reconstruction. All of these efforts were towards a different goal – for demonstration of Wong’s novel approach to perfusion imaging in the human brain. Following SMRM, where a plenary lecture by Tom Brady from MGH opened our eyes to human brain activation imaging using BOLD contrast, and where we learned that EPI was extremely helpful if not critical to its success, we worked quickly to achieve our first results on September 14, 1991. The story is also unique in that Jim Hyde had set up the Biophysics Research Institute to be optimal for just this type of rapidly advancing basic technology research. It was well equipped for hardware development, had open and dynamic collaborative relationships with other departments, hospitals on campus, and GE, and had a relatively flat hierarchy and relaxed, flexible, collegial atmosphere internally. Since these first brain activation results, MCW Biophysics has continued to be at the forefront of functional MRI innovation, having helped to pioneer real time fMRI, high-resolution fMRI, and functional connectivity mapping. PMID:22044784

  14. Epistasis between dopamine regulating genes identifies a nonlinear response of the human hippocampus during memory tasks.

    PubMed

    Bertolino, Alessandro; Di Giorgio, Annabella; Blasi, Giuseppe; Sambataro, Fabio; Caforio, Grazia; Sinibaldi, Lorenzo; Latorre, Valeria; Rampino, Antonio; Taurisano, Paolo; Fazio, Leonardo; Romano, Raffaella; Douzgou, Sofia; Popolizio, Teresa; Kolachana, Bhaskar; Nardini, Marcello; Weinberger, Daniel R; Dallapiccola, Bruno

    2008-08-01

    Dopamine modulation of neuronal activity in prefrontal cortex maps to an inverted U-curve. Dopamine is also an important factor in regulation of hippocampal mediated memory processing. Here, we investigated the effect of genetic variation of dopamine inactivation via catechol-O-methyltransferase (COMT) and the dopamine transporter (DAT) on hippocampal activity in healthy humans during different memory conditions. Using blood oxygenation level-dependent (BOLD) functional magnetic resonance imaging (fMRI) in 82 subjects matched for a series of demographic and genetic variables, we studied the effect of the COMT valine (Val)(158)methionine (Met) and the DAT 3' variable number tandem repeat (VNTR) polymorphisms on function of the hippocampus during encoding of recognition memory and during working memory. Our results consistently demonstrated a double dissociation so that DAT 9-repeat carrier alleles modulated activity in the hippocampus in the exact opposite direction of DAT 10/10-repeat alleles based on COMT Val(158)Met genotype during different memory conditions. Similar results were evident in ventrolateral and dorsolateral prefrontal cortex. These findings suggest that genetically determined dopamine signaling during memory processing maps to a nonlinear relationship also in the hippocampus. Our data also demonstrate in human brain epistasis of two genes implicated in dopamine signaling on brain activity during different memory conditions.

  15. Structure-Function Network Mapping and Its Assessment via Persistent Homology

    PubMed Central

    2017-01-01

    Understanding the relationship between brain structure and function is a fundamental problem in network neuroscience. This work deals with the general method of structure-function mapping at the whole-brain level. We formulate the problem as a topological mapping of structure-function connectivity via matrix function, and find a stable solution by exploiting a regularization procedure to cope with large matrices. We introduce a novel measure of network similarity based on persistent homology for assessing the quality of the network mapping, which enables a detailed comparison of network topological changes across all possible thresholds, rather than just at a single, arbitrary threshold that may not be optimal. We demonstrate that our approach can uncover the direct and indirect structural paths for predicting functional connectivity, and our network similarity measure outperforms other currently available methods. We systematically validate our approach with (1) a comparison of regularized vs. non-regularized procedures, (2) a null model of the degree-preserving random rewired structural matrix, (3) different network types (binary vs. weighted matrices), and (4) different brain parcellation schemes (low vs. high resolutions). Finally, we evaluate the scalability of our method with relatively large matrices (2514x2514) of structural and functional connectivity obtained from 12 healthy human subjects measured non-invasively while at rest. Our results reveal a nonlinear structure-function relationship, suggesting that the resting-state functional connectivity depends on direct structural connections, as well as relatively parsimonious indirect connections via polysynaptic pathways. PMID:28046127

  16. A biochemical landscape of A-to-I RNA editing in the human brain transcriptome

    PubMed Central

    Sakurai, Masayuki; Ueda, Hiroki; Yano, Takanori; Okada, Shunpei; Terajima, Hideki; Mitsuyama, Toutai; Toyoda, Atsushi; Fujiyama, Asao; Kawabata, Hitomi; Suzuki, Tsutomu

    2014-01-01

    Inosine is an abundant RNA modification in the human transcriptome and is essential for many biological processes in modulating gene expression at the post-transcriptional level. Adenosine deaminases acting on RNA (ADARs) catalyze the hydrolytic deamination of adenosines to inosines (A-to-I editing) in double-stranded regions. We previously established a biochemical method called “inosine chemical erasing” (ICE) to directly identify inosines on RNA strands with high reliability. Here, we have applied the ICE method combined with deep sequencing (ICE-seq) to conduct an unbiased genome-wide screening of A-to-I editing sites in the transcriptome of human adult brain. Taken together with the sites identified by the conventional ICE method, we mapped 19,791 novel sites and newly found 1258 edited mRNAs, including 66 novel sites in coding regions, 41 of which cause altered amino acid assignment. ICE-seq detected novel editing sites in various repeat elements as well as in short hairpins. Gene ontology analysis revealed that these edited mRNAs are associated with transcription, energy metabolism, and neurological disorders, providing new insights into various aspects of human brain functions. PMID:24407955

  17. Magnetic resonance spectroscopy of the human brain.

    PubMed

    Ross, B; Bluml, S

    2001-04-01

    Magnetic resonance (MR; synonymous with NMR = nuclear magnetic resonance) is a universal physical technique best known for non-invasive detection and anatomical mapping of water protons (H). MR-spectroscopy (MRS) records protons from tissue chemicals other than water, intrinsic phosphorus containing metabolites, sodium, potassium, carbon, nitrogen, and fluorine. MRS is therefore an imaging technique with the potential to record human and animal biochemistry in vivo. As a result of wide availability of MRI equipment in research laboratories and hospitals, MRS is a serious competitor with PET to define normal body composition and its perturbation by pharmacological and pathological events. This article describes practical aspects of in vivo MRS with particular emphasis on the brain, where novel metabolites have been described. A survey of these new aspects of neurochemistry emphasize their practical utility as neuronal and axonal markers, measures of energy status, membrane constituents, and osmolytes, as well as some xenobiotics, such as alcohol. The concept of multinuclear in vivo MRS is illustrated by diagnosis and therapeutic monitoring of several human brain disorders. Although these methods are currently most frequently encountered in human studies, as well as with transgenic and knockout mouse models, MRS adds a new dimension to anatomic and histopathologic descriptions. Copyright 2001 Wiley-Liss, Inc.

  18. Detailed spatiotemporal brain mapping of chromatic vision combining high-resolution VEP with fMRI and retinotopy.

    PubMed

    Pitzalis, Sabrina; Strappini, Francesca; Bultrini, Alessandro; Di Russo, Francesco

    2018-03-13

    Neuroimaging studies have identified so far, several color-sensitive visual areas in the human brain, and the temporal dynamics of these activities have been separately investigated using the visual-evoked potentials (VEPs). In the present study, we combined electrophysiological and neuroimaging methods to determine a detailed spatiotemporal profile of chromatic VEP and to localize its neural generators. The accuracy of the present co-registration study was obtained by combining standard fMRI data with retinotopic and motion mapping data at the individual level. We found a sequence of occipito activities more complex than that typically reported for chromatic VEPs, including feed-forward and reentrant feedback. Results showed that chromatic human perception arises by the combined activity of at the least five parieto-occipital areas including V1, LOC, V8/VO, and the motion-sensitive dorsal region MT+. However, the contribution of V1 and V8/VO seems dominant because the re-entrant activity in these areas was present more than once (twice in V8/VO and thrice in V1). This feedforward and feedback chromatic processing appears delayed compared with the luminance processing. Associating VEPs and neuroimaging measures, we showed for the first time a complex spatiotemporal pattern of activity, confirming that chromatic stimuli produce intricate interactions of many different brain dorsal and ventral areas. © 2018 Wiley Periodicals, Inc.

  19. A population MRI brain template and analysis tools for the macaque.

    PubMed

    Seidlitz, Jakob; Sponheim, Caleb; Glen, Daniel; Ye, Frank Q; Saleem, Kadharbatcha S; Leopold, David A; Ungerleider, Leslie; Messinger, Adam

    2018-04-15

    The use of standard anatomical templates is common in human neuroimaging, as it facilitates data analysis and comparison across subjects and studies. For non-human primates, previous in vivo templates have lacked sufficient contrast to reliably validate known anatomical brain regions and have not provided tools for automated single-subject processing. Here we present the "National Institute of Mental Health Macaque Template", or NMT for short. The NMT is a high-resolution in vivo MRI template of the average macaque brain generated from 31 subjects, as well as a neuroimaging tool for improved data analysis and visualization. From the NMT volume, we generated maps of tissue segmentation and cortical thickness. Surface reconstructions and transformations to previously published digital brain atlases are also provided. We further provide an analysis pipeline using the NMT that automates and standardizes the time-consuming processes of brain extraction, tissue segmentation, and morphometric feature estimation for anatomical scans of individual subjects. The NMT and associated tools thus provide a common platform for precise single-subject data analysis and for characterizations of neuroimaging results across subjects and studies. Copyright © 2017 ElsevierCompany. All rights reserved.

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

    PubMed Central

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

    2015-01-01

    Deep brain stimulation (DBS) is an established surgical therapy for medically refractory tremor disorders including essential tremor (ET) and is currently under investigation for use in a variety of other neurologic and psychiatric disorders. There is growing evidence that the anti-tremor effects of DBS for ET are directly related to modulation of the dentatorubrothalamic tract (DRT), a white matter pathway that connects the cerebellum, red nucleus, and ventral intermediate nucleus of the thalamus. Emerging white matter targets for DBS, like the DRT, will require improved 3D reference maps of deep brain anatomy and structural connectivity for accurate electrode targeting. High-resolution diffusion MRI of postmortem brain specimens can provide detailed volumetric images of important deep brain nuclei and 3D reconstructions of white matter pathways with probabilistic tractography techniques. We present a high spatial and angular resolution diffusion MRI template of the postmortem human brainstem and thalamus with 3D reconstructions of the nuclei and white matter tracts involved in ET circuitry. We demonstrate accurate registration of these data to in vivo, clinical images from patients receiving DBS therapy, and correlate electrode proximity to tractography of the DRT with improvement of ET symptoms. PMID:26043869

  1. Causal mapping of emotion networks in the human brain: Framework and initial findings.

    PubMed

    Dubois, Julien; Oya, Hiroyuki; Tyszka, J Michael; Howard, Matthew; Eberhardt, Frederick; Adolphs, Ralph

    2017-11-13

    Emotions involve many cortical and subcortical regions, prominently including the amygdala. It remains unknown how these multiple network components interact, and it remains unknown how they cause the behavioral, autonomic, and experiential effects of emotions. Here we describe a framework for combining a novel technique, concurrent electrical stimulation with fMRI (es-fMRI), together with a novel analysis, inferring causal structure from fMRI data (causal discovery). We outline a research program for investigating human emotion with these new tools, and provide initial findings from two large resting-state datasets as well as case studies in neurosurgical patients with electrical stimulation of the amygdala. The overarching goal is to use causal discovery methods on fMRI data to infer causal graphical models of how brain regions interact, and then to further constrain these models with direct stimulation of specific brain regions and concurrent fMRI. We conclude by discussing limitations and future extensions. The approach could yield anatomical hypotheses about brain connectivity, motivate rational strategies for treating mood disorders with deep brain stimulation, and could be extended to animal studies that use combined optogenetic fMRI. Copyright © 2017 Elsevier Ltd. All rights reserved.

  2. The myth of the normal, average human brain--the ICBM experience: (1) subject screening and eligibility.

    PubMed

    Mazziotta, John C; Woods, Roger; Iacoboni, Marco; Sicotte, Nancy; Yaden, Kami; Tran, Mary; Bean, Courtney; Kaplan, Jonas; Toga, Arthur W

    2009-02-01

    In the course of developing an atlas and reference system for the normal human brain throughout the human age span from structural and functional brain imaging data, the International Consortium for Brain Mapping (ICBM) developed a set of "normal" criteria for subject inclusion and the associated exclusion criteria. The approach was to minimize inclusion of subjects with any medical disorders that could affect brain structure or function. In the past two years, a group of 1685 potential subjects responded to solicitation advertisements at one of the consortium sites (UCLA). Subjects were screened by a detailed telephone interview and then had an in-person history and physical examination. Of those who responded to the advertisement and considered themselves to be normal, only 31.6% (532 subjects) passed the telephone screening process. Of the 348 individuals who submitted to in-person history and physical examinations, only 51.7% passed these screening procedures. Thus, only 10.7% of those individuals who responded to the original advertisement qualified for imaging. The most frequent cause for exclusion in the second phase of subject screening was high blood pressure followed by abnormal signs on neurological examination. It is concluded that the majority of individuals who consider themselves normal by self-report are found not to be so by detailed historical interviews about underlying medical conditions and by thorough medical and neurological examinations. Recommendations are made with regard to the inclusion of subjects in brain imaging studies and the criteria used to select them.

  3. Architecture of cognitive flexibility revealed by lesion mapping

    PubMed Central

    Barbey, Aron K.; Colom, Roberto; Grafman, Jordan

    2013-01-01

    Neuroscience has made remarkable progress in understanding the architecture of human intelligence, identifying a distributed network of brain structures that support goal-directed, intelligent behavior. However, the neural foundations of cognitive flexibility and adaptive aspects of intellectual function remain to be well characterized. Here, we report a human lesion study (n = 149) that investigates the neural bases of key competencies of cognitive flexibility (i.e., mental flexibility and the fluent generation of new ideas) and systematically examine their contributions to a broad spectrum of cognitive and social processes, including psychometric intelligence (Wechsler Adult Intelligence Scale), emotional intelligence (Mayer, Salovey, Caruso Emotional Intelligence Test), and personality (Neuroticism–Extraversion–Openness Personality Inventory). Latent variable modeling was applied to obtain error-free indices of each factor, followed by voxel-based lesion-symptom mapping to elucidate their neural substrates. Regression analyses revealed that latent scores for psychometric intelligence reliably predict latent scores for cognitive flexibility (adjusted R2 = 0.94). Lesion mapping results further indicated that these convergent processes depend on a shared network of frontal, temporal, and parietal regions, including white matter association tracts, which bind these areas into an integrated system. A targeted analysis of the unique variance explained by cognitive flexibility further revealed selective damage within the right superior temporal gyrus, a region known to support insight and the recognition of novel semantic relations. The observed findings motivate an integrative framework for understanding the neural foundations of adaptive behavior, suggesting that core elements of cognitive flexibility emerge from a distributed network of brain regions that support specific competencies for human intelligence. PMID:23721727

  4. The structure of creative cognition in the human brain

    PubMed Central

    Jung, Rex E.; Mead, Brittany S.; Carrasco, Jessica; Flores, Ranee A.

    2013-01-01

    Creativity is a vast construct, seemingly intractable to scientific inquiry—perhaps due to the vague concepts applied to the field of research. One attempt to limit the purview of creative cognition formulates the construct in terms of evolutionary constraints, namely that of blind variation and selective retention (BVSR). Behaviorally, one can limit the “blind variation” component to idea generation tests as manifested by measures of divergent thinking. The “selective retention” component can be represented by measures of convergent thinking, as represented by measures of remote associates. We summarize results from measures of creative cognition, correlated with structural neuroimaging measures including structural magnetic resonance imaging (sMRI), diffusion tensor imaging (DTI), and proton magnetic resonance spectroscopy (1H-MRS). We also review lesion studies, considered to be the “gold standard” of brain-behavioral studies. What emerges is a picture consistent with theories of disinhibitory brain features subserving creative cognition, as described previously (Martindale, 1981). We provide a perspective, involving aspects of the default mode network (DMN), which might provide a “first approximation” regarding how creative cognition might map on to the human brain. PMID:23847503

  5. Using regional homogeneity to reveal altered spontaneous activity in patients with mild cognitive impairment.

    PubMed

    Wang, Yumei; Zhao, Xiaochuan; Xu, Shunjiang; Yu, Lulu; Wang, Lan; Song, Mei; Yang, Linlin; Wang, Xueyi

    2015-01-01

    Most patients with mild cognitive impairment (MCI) are thought to be in an early stage of Alzheimer's disease (AD). Resting-state functional magnetic resonance imaging reflects spontaneous brain activity and/or the endogenous/background neurophysiological process of the human brain. Regional homogeneity (ReHo) rapidly maps regional brain activity across the whole brain. In the present study, we used the ReHo index to explore whole brain spontaneous activity pattern in MCI. Our results showed that MCI subjects displayed an increased ReHo index in the paracentral lobe, precuneus, and postcentral and a decreased ReHo index in the medial temporal gyrus and hippocampus. Impairments in the medial temporal gyrus and hippocampus may serve as important markers distinguishing MCI from healthy aging. Moreover, the increased ReHo index observed in the postcentral and paracentral lobes might indicate compensation for the cognitive function losses in individuals with MCI.

  6. Using Regional Homogeneity to Reveal Altered Spontaneous Activity in Patients with Mild Cognitive Impairment

    PubMed Central

    Wang, Yumei; Zhao, Xiaochuan; Xu, Shunjiang; Yu, Lulu; Wang, Lan; Song, Mei; Yang, Linlin; Wang, Xueyi

    2015-01-01

    Most patients with mild cognitive impairment (MCI) are thought to be in an early stage of Alzheimer's disease (AD). Resting-state functional magnetic resonance imaging reflects spontaneous brain activity and/or the endogenous/background neurophysiological process of the human brain. Regional homogeneity (ReHo) rapidly maps regional brain activity across the whole brain. In the present study, we used the ReHo index to explore whole brain spontaneous activity pattern in MCI. Our results showed that MCI subjects displayed an increased ReHo index in the paracentral lobe, precuneus, and postcentral and a decreased ReHo index in the medial temporal gyrus and hippocampus. Impairments in the medial temporal gyrus and hippocampus may serve as important markers distinguishing MCI from healthy aging. Moreover, the increased ReHo index observed in the postcentral and paracentral lobes might indicate compensation for the cognitive function losses in individuals with MCI. PMID:25738156

  7. Stimulation-Based Control of Dynamic Brain Networks

    PubMed Central

    Pasqualetti, Fabio; Gu, Shi; Cieslak, Matthew

    2016-01-01

    The ability to modulate brain states using targeted stimulation is increasingly being employed to treat neurological disorders and to enhance human performance. Despite the growing interest in brain stimulation as a form of neuromodulation, much remains unknown about the network-level impact of these focal perturbations. To study the system wide impact of regional stimulation, we employ a data-driven computational model of nonlinear brain dynamics to systematically explore the effects of targeted stimulation. Validating predictions from network control theory, we uncover the relationship between regional controllability and the focal versus global impact of stimulation, and we relate these findings to differences in the underlying network architecture. Finally, by mapping brain regions to cognitive systems, we observe that the default mode system imparts large global change despite being highly constrained by structural connectivity. This work forms an important step towards the development of personalized stimulation protocols for medical treatment or performance enhancement. PMID:27611328

  8. 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.

  9. The challenge of mapping the human connectome based on diffusion tractography.

    PubMed

    Maier-Hein, Klaus H; Neher, Peter F; Houde, Jean-Christophe; Côté, Marc-Alexandre; Garyfallidis, Eleftherios; Zhong, Jidan; Chamberland, Maxime; Yeh, Fang-Cheng; Lin, Ying-Chia; Ji, Qing; Reddick, Wilburn E; Glass, John O; Chen, David Qixiang; Feng, Yuanjing; Gao, Chengfeng; Wu, Ye; Ma, Jieyan; Renjie, H; Li, Qiang; Westin, Carl-Fredrik; Deslauriers-Gauthier, Samuel; González, J Omar Ocegueda; Paquette, Michael; St-Jean, Samuel; Girard, Gabriel; Rheault, François; Sidhu, Jasmeen; Tax, Chantal M W; Guo, Fenghua; Mesri, Hamed Y; Dávid, Szabolcs; Froeling, Martijn; Heemskerk, Anneriet M; Leemans, Alexander; Boré, Arnaud; Pinsard, Basile; Bedetti, Christophe; Desrosiers, Matthieu; Brambati, Simona; Doyon, Julien; Sarica, Alessia; Vasta, Roberta; Cerasa, Antonio; Quattrone, Aldo; Yeatman, Jason; Khan, Ali R; Hodges, Wes; Alexander, Simon; Romascano, David; Barakovic, Muhamed; Auría, Anna; Esteban, Oscar; Lemkaddem, Alia; Thiran, Jean-Philippe; Cetingul, H Ertan; Odry, Benjamin L; Mailhe, Boris; Nadar, Mariappan S; Pizzagalli, Fabrizio; Prasad, Gautam; Villalon-Reina, Julio E; Galvis, Justin; Thompson, Paul M; Requejo, Francisco De Santiago; Laguna, Pedro Luque; Lacerda, Luis Miguel; Barrett, Rachel; Dell'Acqua, Flavio; Catani, Marco; Petit, Laurent; Caruyer, Emmanuel; Daducci, Alessandro; Dyrby, Tim B; Holland-Letz, Tim; Hilgetag, Claus C; Stieltjes, Bram; Descoteaux, Maxime

    2017-11-07

    Tractography based on non-invasive diffusion imaging is central to the study of human brain connectivity. To date, the approach has not been systematically validated in ground truth studies. Based on a simulated human brain data set with ground truth tracts, we organized an open international tractography challenge, which resulted in 96 distinct submissions from 20 research groups. Here, we report the encouraging finding that most state-of-the-art algorithms produce tractograms containing 90% of the ground truth bundles (to at least some extent). However, the same tractograms contain many more invalid than valid bundles, and half of these invalid bundles occur systematically across research groups. Taken together, our results demonstrate and confirm fundamental ambiguities inherent in tract reconstruction based on orientation information alone, which need to be considered when interpreting tractography and connectivity results. Our approach provides a novel framework for estimating reliability of tractography and encourages innovation to address its current limitations.

  10. Determining Optimal Microwave Antigen Retrieval Conditions for Microtubule-Associated Protein 2 Immunohistochemistry in the Guinea Pig Brain

    DTIC Science & Technology

    2002-12-01

    sections of formalin-fixed guinea pig brains using different MAP-2 monoclonal antibodies. Brain sections were boiled in sodium citrate, citric acid...citric acid solution at pH 6.0 is the optimal microwave-assisted AR method for immunolabeling MAP-2 in formalin-fixed, paraffin-processed guinea pig brain...studies on archival guinea pig brain paraffin blocks, ultimately relaxing the use of additional animals to evaluate changes in MAP-2 expression between chemical warfare nerve agent-treated and control samples.

  11. Mental and Physical (MAP) Training: a neurogenesis-inspired intervention that enhances health in humans.

    PubMed

    Shors, Tracey J; Olson, Ryan L; Bates, Marsha E; Selby, Edward A; Alderman, Brandon L

    2014-11-01

    New neurons are generated in the hippocampus each day and their survival is greatly enhanced through effortful learning (Shors, 2014). The numbers of cells produced can be increased by physical exercise (van Praag, Kempermann, & Gage, 1999). These findings inspired us to develop a clinical intervention for humans known as Mental and Physical Training, or MAP Training. Each session consists of 30min of mental training with focused attention meditation (20min sitting and 10min walking). Meditation is an effortful training practice that involves learning about the transient nature of thoughts and thought patterns, and acquiring skills to recognize them without necessarily attaching meaning and/or emotions to them. The mental training component is followed by physical training with 30min of aerobic exercise performed at moderate intensity. During this component, participants learn choreographed dance routines while engaging in aerobic exercise. In a pilot "proof-of-concept" study, we provided supervised MAP Training (2 sessions per week for 8weeks) to a group of young mothers in the local community who were recently homeless, most of them having previously suffered from physical and sexual abuse, addiction, and depression. Preliminary data suggest that MAP Training improves dependent measures of aerobic fitness (as assessed by maximal rate of oxygen consumed) while decreasing symptoms of depression and anxiety. Similar changes were not observed in a group of recently homeless women who did not participate in MAP Training. It is not currently possible to determine whether new neurons in the human brain increase in number as a result of MAP Training. Rather these preliminary results of MAP Training illustrate how neuroscientific research can be translated into novel clinical interventions that benefit human health and wellness. Copyright © 2014 Elsevier Inc. All rights reserved.

  12. Defining functional SMA and pre-SMA subregions in human MFC using resting state fMRI: functional connectivity-based parcellation method.

    PubMed

    Kim, Jae-Hun; Lee, Jong-Min; Jo, Hang Joon; Kim, Sook Hui; Lee, Jung Hee; Kim, Sung Tae; Seo, Sang Won; Cox, Robert W; Na, Duk L; Kim, Sun I; Saad, Ziad S

    2010-02-01

    Noninvasive parcellation of the human cerebral cortex is an important goal for understanding and examining brain functions. Recently, the patterns of anatomical connections using diffusion tensor imaging (DTI) have been used to parcellate brain regions. Here, we present a noninvasive parcellation approach that uses "functional fingerprints" obtained by correlation measures on resting state functional magnetic resonance imaging (fMRI) data to parcellate brain regions. In other terms, brain regions are parcellated based on the similarity of their connection--as reflected by correlation during resting state--to the whole brain. The proposed method was used to parcellate the medial frontal cortex (MFC) into supplementary motor areas (SMA) and pre-SMA subregions. In agreement with anatomical landmark-based parcellation, we find that functional fingerprint clustering of the MFC results in anterior and posterior clusters. The probabilistic maps from 12 subjects showed that the anterior cluster is mainly located rostral to the vertical commissure anterior (VCA) line, whereas the posterior cluster is mainly located caudal to VCA line, suggesting the homologues of pre-SMA and SMA. The functional connections from the putative pre-SMA cluster were connected to brain regions which are responsible for complex/cognitive motor control, whereas those from the putative SMA cluster were connected to brain regions which are related to the simple motor control. These findings demonstrate the feasibility of the functional connectivity-based parcellation of the human cerebral cortex using resting state fMRI. Copyright (c) 2009 Elsevier Inc. All rights reserved.

  13. Automatic cortical thickness analysis on rodent brain

    NASA Astrophysics Data System (ADS)

    Lee, Joohwi; Ehlers, Cindy; Crews, Fulton; Niethammer, Marc; Budin, Francois; Paniagua, Beatriz; Sulik, Kathy; Johns, Josephine; Styner, Martin; Oguz, Ipek

    2011-03-01

    Localized difference in the cortex is one of the most useful morphometric traits in human and animal brain studies. There are many tools and methods already developed to automatically measure and analyze cortical thickness for the human brain. However, these tools cannot be directly applied to rodent brains due to the different scales; even adult rodent brains are 50 to 100 times smaller than humans. This paper describes an algorithm for automatically measuring the cortical thickness of mouse and rat brains. The algorithm consists of three steps: segmentation, thickness measurement, and statistical analysis among experimental groups. The segmentation step provides the neocortex separation from other brain structures and thus is a preprocessing step for the thickness measurement. In the thickness measurement step, the thickness is computed by solving a Laplacian PDE and a transport equation. The Laplacian PDE first creates streamlines as an analogy of cortical columns; the transport equation computes the length of the streamlines. The result is stored as a thickness map over the neocortex surface. For the statistical analysis, it is important to sample thickness at corresponding points. This is achieved by the particle correspondence algorithm which minimizes entropy between dynamically moving sample points called particles. Since the computational cost of the correspondence algorithm may limit the number of corresponding points, we use thin-plate spline based interpolation to increase the number of corresponding sample points. As a driving application, we measured the thickness difference to assess the effects of adolescent intermittent ethanol exposure that persist into adulthood and performed t-test between the control and exposed rat groups. We found significantly differing regions in both hemispheres.

  14. Cloning, characterization, and chromosomal mapping of a human electroneutral Na(+)-driven Cl-HCO3 exchanger.

    PubMed

    Grichtchenko, I I; Choi, I; Zhong, X; Bray-Ward, P; Russell, J M; Boron, W F

    2001-03-16

    The electroneutral Na(+)-driven Cl-HCO3 exchanger is a key mechanism for regulating intracellular pH (pH(i)) in neurons, glia, and other cells. Here we report the cloning, tissue distribution, chromosomal location, and functional characterization of the cDNA of such a transporter (NDCBE1) from human brain (GenBank accession number AF069512). NDCBE1, which encodes 1044 amino acids, is 34% identical to the mammalian anion exchanger (AE2); approximately 50% to the electrogenic Na/HCO3 cotransporter (NBCe1) from salamander, rat, and humans; approximately 73% to mammalian electroneutral Na/HCO3 cotransporters (NBCn1); 71% to mouse NCBE; and 47% to a Na(+)-driven anion exchanger (NDAE1) from Drosophila. Northern blot analysis of NDCBE1 shows a robust approximately 12-kilobase signal in all major regions of human brain and in testis, and weaker signals in kidney and ovary. This human gene (SLC4A8) maps to chromosome 12q13. When expressed in Xenopus oocytes and running in the forward direction, NDCBE1 is electroneutral and mediates increases in both pH(i) and [Na(+)](i) (monitored with microelectrodes) that require HCO3(-) and are blocked by 4,4'-diisothiocyanostilbene-2,2'-disulfonic acid (DIDS). The pH(i) increase also requires extracellular Na(+). The Na(+):HCO3(-) stoichiometry is 1:2. Forward-running NDCBE1 mediates a 36Cl efflux that requires extracellular Na(+) and HCO3(-) and is blocked by DIDS. Running in reverse, NDCBE1 requires extracellular Cl(-). Thus, NDCBE1 encodes a human, electroneutral Na(+)-driven Cl-HCO3 exchanger.

  15. Computation and brain processes, with special reference to neuroendocrine systems.

    PubMed

    Toni, Roberto; Spaletta, Giulia; Casa, Claudia Della; Ravera, Simone; Sandri, Giorgio

    2007-01-01

    The development of neural networks and brain automata has made neuroscientists aware that the performance limits of these brain-like devices lies, at least in part, in their computational power. The computational basis of a. standard cybernetic design, in fact, refers to that of a discrete and finite state machine or Turing Machine (TM). In contrast, it has been suggested that a number of human cerebral activites, from feedback controls up to mental processes, rely on a mixing of both finitary, digital-like and infinitary, continuous-like procedures. Therefore, the central nervous system (CNS) of man would exploit a form of computation going beyond that of a TM. This "non conventional" computation has been called hybrid computation. Some basic structures for hybrid brain computation are believed to be the brain computational maps, in which both Turing-like (digital) computation and continuous (analog) forms of calculus might occur. The cerebral cortex and brain stem appears primary candidate for this processing. However, also neuroendocrine structures like the hypothalamus are believed to exhibit hybrid computional processes, and might give rise to computational maps. Current theories on neural activity, including wiring and volume transmission, neuronal group selection and dynamic evolving models of brain automata, bring fuel to the existence of natural hybrid computation, stressing a cooperation between discrete and continuous forms of communication in the CNS. In addition, the recent advent of neuromorphic chips, like those to restore activity in damaged retina and visual cortex, suggests that assumption of a discrete-continuum polarity in designing biocompatible neural circuitries is crucial for their ensuing performance. In these bionic structures, in fact, a correspondence exists between the original anatomical architecture and synthetic wiring of the chip, resulting in a correspondence between natural and cybernetic neural activity. Thus, chip "form" provides a continuum essential to chip "function". We conclude that it is reasonable to predict the existence of hybrid computational processes in the course of many human, brain integrating activities, urging development of cybernetic approaches based on this modelling for adequate reproduction of a variety of cerebral performances.

  16. Neuromodulation: Selected approaches and challenges

    PubMed Central

    Parpura, Vladimir; Silva, Gabriel A.; Tass, Peter A.; Bennet, Kevin E.; Meyyappan, Meyya; Koehne, Jessica; Lee, Kendall H.; Andrews, Russell J.

    2012-01-01

    The brain operates through complex interactions in the flow of information and signal processing within neural networks. The “wiring” of such networks, being neuronal or glial, can physically and/or functionally go rogue in various pathological states. Neuromodulation, as a multidisciplinary venture, attempts to correct such faulty nets. In this review, selected approaches and challenges in neuromoduation are discussed. The use of water-dispersible carbon nanotubes have proven effective in modulation of neurite outgrowth in culture as well as in aiding regeneration after spinal cord injury in vivo. Studying neural circuits using computational biology and analytical engineering approaches brings to light geometrical mapping of dynamics within neural networks, much needed information for stimulation interventions in medical practice. Indeed, sophisticated desynchronization approaches used for brain stimulation have been successful in coaxing “misfiring” neuronal circuits to resume productive firing patterns in various human disorders. Devices have been developed for the real time measurement of various neurotransmitters as well as electrical activity in the human brain during electrical deep brain stimulation. Such devices can establish the dynamics of electrochemical changes in the brain during stimulation. With increasing application of nanomaterials in devices for electrical and chemical recording and stimulating in the brain, the era of cellular, and even intracellular, precision neuromodulation will soon be upon us. PMID:23190025

  17. Impact of correction factors in human brain lesion-behavior inference.

    PubMed

    Sperber, Christoph; Karnath, Hans-Otto

    2017-03-01

    Statistical voxel-based lesion-behavior mapping (VLBM) in neurological patients with brain lesions is frequently used to examine the relationship between structure and function of the healthy human brain. Only recently, two simulation studies noted reduced anatomical validity of this method, observing the results of VLBM to be systematically misplaced by about 16 mm. However, both simulation studies differed from VLBM analyses of real data in that they lacked the proper use of two correction factors: lesion size and "sufficient lesion affection." In simulation experiments on a sample of 274 real stroke patients, we found that the use of these two correction factors reduced misplacement markedly compared to uncorrected VLBM. Apparently, the misplacement is due to physiological effects of brain lesion anatomy. Voxel-wise topographies of collateral damage in the real data were generated and used to compute a metric for the inter-voxel relation of brain damage. "Anatomical bias" vectors that were solely calculated from these inter-voxel relations in the patients' real anatomical data, successfully predicted the VLBM misplacement. The latter has the potential to help in the development of new VLBM methods that provide even higher anatomical validity than currently available by the proper use of correction factors. Hum Brain Mapp 38:1692-1701, 2017. © 2017 Wiley Periodicals, Inc. © 2017 Wiley Periodicals, Inc.

  18. Electrical Stimulation Modulates High γ Activity and Human Memory Performance

    PubMed Central

    Berry, Brent M.; Miller, Laura R.; Khadjevand, Fatemeh; Ezzyat, Youssef; Wanda, Paul; Sperling, Michael R.; Lega, Bradley; Stead, S. Matt

    2018-01-01

    Direct electrical stimulation of the brain has emerged as a powerful treatment for multiple neurological diseases, and as a potential technique to enhance human cognition. Despite its application in a range of brain disorders, it remains unclear how stimulation of discrete brain areas affects memory performance and the underlying electrophysiological activities. Here, we investigated the effect of direct electrical stimulation in four brain regions known to support declarative memory: hippocampus (HP), parahippocampal region (PH) neocortex, prefrontal cortex (PF), and lateral temporal cortex (TC). Intracranial EEG recordings with stimulation were collected from 22 patients during performance of verbal memory tasks. We found that high γ (62–118 Hz) activity induced by word presentation was modulated by electrical stimulation. This modulatory effect was greatest for trials with “poor” memory encoding. The high γ modulation correlated with the behavioral effect of stimulation in a given brain region: it was negative, i.e., the induced high γ activity was decreased, in the regions where stimulation decreased memory performance, and positive in the lateral TC where memory enhancement was observed. Our results suggest that the effect of electrical stimulation on high γ activity induced by word presentation may be a useful biomarker for mapping memory networks and guiding therapeutic brain stimulation. PMID:29404403

  19. Large-scale brain networks are distinctly affected in right and left mesial temporal lobe epilepsy.

    PubMed

    de Campos, Brunno Machado; Coan, Ana Carolina; Lin Yasuda, Clarissa; Casseb, Raphael Fernandes; Cendes, Fernando

    2016-09-01

    Mesial temporal lobe epilepsy (MTLE) with hippocampus sclerosis (HS) is associated with functional and structural alterations extending beyond the temporal regions and abnormal pattern of brain resting state networks (RSNs) connectivity. We hypothesized that the interaction of large-scale RSNs is differently affected in patients with right- and left-MTLE with HS compared to controls. We aimed to determine and characterize these alterations through the analysis of 12 RSNs, functionally parceled in 70 regions of interest (ROIs), from resting-state functional-MRIs of 99 subjects (52 controls, 26 right- and 21 left-MTLE patients with HS). Image preprocessing and statistical analysis were performed using UF(2) C-toolbox, which provided ROI-wise results for intranetwork and internetwork connectivity. Intranetwork abnormalities were observed in the dorsal default mode network (DMN) in both groups of patients and in the posterior salience network in right-MTLE. Both groups showed abnormal correlation between the dorsal-DMN and the posterior salience, as well as between the dorsal-DMN and the executive-control network. Patients with left-MTLE also showed reduced correlation between the dorsal-DMN and visuospatial network and increased correlation between bilateral thalamus and the posterior salience network. The ipsilateral hippocampus stood out as a central area of abnormalities. Alterations on left-MTLE expressed a low cluster coefficient, whereas the altered connections on right-MTLE showed low cluster coefficient in the DMN but high in the posterior salience regions. Both right- and left-MTLE patients with HS have widespread abnormal interactions of large-scale brain networks; however, all parameters evaluated indicate that left-MTLE has a more intricate bihemispheric dysfunction compared to right-MTLE. Hum Brain Mapp 37:3137-3152, 2016. © 2016 The Authors Human Brain Mapping Published by Wiley Periodicals, Inc. © 2016 The Authors Human Brain Mapping Published by Wiley Periodicals, Inc.

  20. Ex-vivo quantitative susceptibility mapping of human brain hemispheres

    PubMed Central

    Kotrotsou, Aikaterini; Tamhane, Ashish A.; Dawe, Robert J.; Kapasi, Alifiya; Leurgans, Sue E.; Schneider, Julie A.; Bennett, David A.; Arfanakis, Konstantinos

    2017-01-01

    Ex-vivo brain quantitative susceptibility mapping (QSM) allows investigation of brain characteristics at essentially the same point in time as histopathologic examination, and therefore has the potential to become an important tool for determining the role of QSM as a diagnostic and monitoring tool of age-related neuropathologies. In order to be able to translate the ex-vivo QSM findings to in-vivo, it is crucial to understand the effects of death and chemical fixation on brain magnetic susceptibility measurements collected ex-vivo. Thus, the objective of this work was twofold: a) to assess the behavior of magnetic susceptibility in both gray and white matter of human brain hemispheres as a function of time postmortem, and b) to establish the relationship between in-vivo and ex-vivo gray matter susceptibility measurements on the same hemispheres. Five brain hemispheres from community-dwelling older adults were imaged ex-vivo with QSM on a weekly basis for six weeks postmortem, and the longitudinal behavior of ex-vivo magnetic susceptibility in both gray and white matter was assessed. The relationship between in-vivo and ex-vivo gray matter susceptibility measurements was investigated using QSM data from eleven older adults imaged both antemortem and postmortem. No systematic change in ex-vivo magnetic susceptibility of gray or white matter was observed over time postmortem. Additionally, it was demonstrated that, gray matter magnetic susceptibility measured ex-vivo may be well modeled as a linear function of susceptibility measured in-vivo. In conclusion, magnetic susceptibility in gray and white matter measured ex-vivo with QSM does not systematically change in the first six weeks after death. This information is important for future cross-sectional ex-vivo QSM studies of hemispheres imaged at different postmortem intervals. Furthermore, the linear relationship between in-vivo and ex-vivo gray matter magnetic susceptibility suggests that ex-vivo QSM captures information linked to antemortem gray matter magnetic susceptibility, which is important for translation of ex-vivo QSM findings to in-vivo. PMID:29261693

  1. fMRI study of neural sensitization to hedonic stimuli in long-term, daily cannabis users.

    PubMed

    Filbey, Francesca M; Dunlop, Joseph; Ketcherside, Ariel; Baine, Jessica; Rhinehardt, Tyler; Kuhn, Brittany; DeWitt, Sam; Alvi, Talha

    2016-10-01

    Although there is emergent evidence illustrating neural sensitivity to cannabis cues in cannabis users, the specificity of this effect to cannabis cues as opposed to a generalized hyper-sensitivity to hedonic stimuli has not yet been directly tested. Using fMRI, we presented 53 daily, long-term cannabis users and 68 non-using controls visual and tactile cues for cannabis, a natural reward, and, a sensory-perceptual control object to evaluate brain response to hedonic stimuli in cannabis users. The results showed an interaction between group and reward type such that the users had greater response during cannabis cues relative to natural reward cues (i.e., fruit) in the orbitofrontal cortex, striatum, anterior cingulate gyrus, and ventral tegmental area compared to non-users (cluster-threshold z = 2.3, P < 0.05). In the users, there were positive brain-behavior correlations between neural response to cannabis cues in fronto-striatal-temporal regions and subjective craving, marijuana-related problems, withdrawal symptoms, and levels of THC metabolites (cluster-threshold z = 2.3, P < 0.05). These findings demonstrate hyper-responsivity, and, specificity of brain response to cannabis cues in long-term cannabis users that are above that of response to natural reward cues. These observations are concordant with incentive sensitization models suggesting sensitization of mesocorticolimbic regions and disruption of natural reward processes following drug use. Although the cross-sectional nature of this study does not provide information on causality, the positive correlations between neural response and indicators of cannabis use (i.e., THC levels) suggest that alterations in the reward system are, in part, related to cannabis use. Hum Brain Mapp 37:3431-3443, 2016. © 2016 The Authors Human Brain Mapping Published by Wiley Periodicals, Inc. © 2016 The Authors Human Brain Mapping Published by Wiley Periodicals, Inc.

  2. Brain protection of nicergoline against hypoxia: EEG brain mapping and psychometry.

    PubMed

    Saletu, B; Grünberger, J; Linzmayer, L; Anderer, P

    1990-01-01

    In a double-blind, placebo-controlled trial human brain function and mental performance as well as the antihypoxidotic properties of nicergoline were studied utilizing blood gas analysis, EEG brain mapping and psychometry. Hypoxic hypoxidosis was experimentally induced by a fixed gas combination of 9.8% oxygen (O2) and 90.2% nitrogen (N2) equivalent to 6,000 m altitude, which was inhaled for 23 min under normobaric conditions by 16 healthy volunteers. They received randomized after an adaptation session placebo, 10 mg, 30 mg and 60 mg nicergoline (NIC). Evaluation of blood gases, brain mapping and psychometry was carried out at 0, 2, 4, 6, 8 hrs oral drug administration. Blood gas analysis demonstrated a drop in PO2 from 95 to 35 and 34 mm Hg in the 14 and 23 min of inhalation, respectively. PCO2 decreased too (38 to 34 and 34 mm Hg), while pH increased (7.39 to 7.44 and 7.44). Base excess increased (-0.6 to 0.6 and 0.4) while standard bicarbonate decreased (24.4 to 24.1 and 23.8 mmol/l). Thus, blood gases remained stable between the 14 and 23 min of hypoxia during which time the neurophysiological and behavioral evaluations were carried out. EEG brain mapping exhibited an increase in delta/theta activity mostly over the parietal, temporal and central regions (left more than right), while alpha activity decreased (mostly over the parietal, central, frontal, fronto-temporal and temporo-occipital regions). 30 and 60 mg NIC attenuated this deterioration of vigilance. At the behavioral level, hypoxic hypoxidosis induced a deterioration of the noo- and thymospsyche which was mitigated by NIC. Based on 13 psychometric variables, the hypoxia-induced performance decrement was on the overall (2nd-8th hr) 43% after placebo as compared with pretreatment normoxic values, while only 29, 24 and 31% after 10, 30 and 60 mg nicergoline, respectively. The difference between placebo and the optimal dosage of nicergoline 30 mg reached the level of statistical significance (p less than 0.01, multiple Wilcoxon).

  3. Quantitative autoradiographic mapping of herpes simplex virus encephalitis with a radiolabeled antiviral drug

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

    Saito, Y.; Price, R.W.; Rottenberg, D.A.

    1982-09-17

    2'-Fluoro-5-methyl-1-..beta..-D-arabinosyluracil (FMAU) labeled with carbon-14 was used to image herpes simplex virus type 1-infected regions of rat brain by quantitative autoradiography. FMAU is a potent antiviral pyrimidine nucleoside which is selectively phosphorylated by virus-coded thymidine kinase. When the labeled FMAU was administered 6 hours before the rats were killed, the selective uptake and concentration of the drug and its metabolites by infected cells (defined by immunoperoxidase staining of viral antigens) allowed quantitative definition and mapping of HSV-1-infected structures in autoradiograms of brain sections. These results shown that quantitative autoradiography can be used to characterize the local metabolism of antiviral drugsmore » by infected cells in vivo. They also suggest that the selective uptake of drugs that exploit viral thymidine kinase for their antiviral effect can, by appropriate labeling, be used in conjunction with clinical neuroimaging techniques to define infected regions of human brain, thereby providing a new approach to the diagnosis of herpes encephalitis in man.« less

  4. New techniques for positron emission tomography in the study of human neurological disorders for the period June 15, 1987 through December 14, 1987

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

    Kuhl, D.E.

    1987-09-01

    A brief progress report is presented describing the preparation of /sup 11/C-scopolamine, /sup 17/F-fluoromethane and /sup 18/F-tetraalkylammonium fluoride. The application of /sup 11/C-scopolamine to map cholinergic receptors in normal human brain. Additional studies entitled ''The Automated Arterial Blood Sampling Systems for PET'' and ''Investigations of Array Processor Based High-Speed Parameter Estimation for Tracer Kinetic Modeling'' are also described. (DT)

  5. Visualisation of Massive Military Datasets: Human Factors, Applications, and Technologies

    DTIC Science & Technology

    2001-05-01

    we have been confronted with data of new kinds at a rate faster than our human brains can manage to turn into information. “Visualisation” means the...because variation of these kinds do not have the qaulities of textons. Figure 2.5 A trivial Icon Map in which there is a data attribute, shown as...information management is to ensure that the right information is available to the right person, at the right time, and shown in such a way that the person

  6. Brain serotonin transporter density and aggression in abstinent methamphetamine abusers.

    PubMed

    Sekine, Yoshimoto; Ouchi, Yasuomi; Takei, Nori; Yoshikawa, Etsuji; Nakamura, Kazuhiko; Futatsubashi, Masami; Okada, Hiroyuki; Minabe, Yoshio; Suzuki, Katsuaki; Iwata, Yasuhide; Tsuchiya, Kenji J; Tsukada, Hideo; Iyo, Masaomi; Mori, Norio

    2006-01-01

    In animals, methamphetamine is known to have a neurotoxic effect on serotonin neurons, which have been implicated in the regulation of mood, anxiety, and aggression. It remains unknown whether methamphetamine damages serotonin neurons in humans. To investigate the status of brain serotonin neurons and their possible relationship with clinical characteristics in currently abstinent methamphetamine abusers. Case-control analysis. A hospital research center. Twelve currently abstinent former methamphetamine abusers (5 women and 7 men) and 12 age-, sex-, and education-matched control subjects recruited from the community. The brain regional density of the serotonin transporter, a structural component of serotonin neurons, was estimated using positron emission tomography and trans-1,2,3,5,6,10-beta-hexahydro-6-[4-(methylthio)phenyl]pyrrolo-[2,1-a]isoquinoline ([(11)C](+)McN-5652). Estimates were derived from region-of-interest and statistical parametric mapping methods, followed by within-case analysis using the measures of clinical variables. The duration of methamphetamine use, the magnitude of aggression and depressive symptoms, and changes in serotonin transporter density represented by the [(11)C](+)McN-5652 distribution volume. Methamphetamine abusers showed increased levels of aggression compared with controls. Region-of-interest and statistical parametric mapping analyses revealed that the serotonin transporter density in global brain regions (eg, the midbrain, thalamus, caudate, putamen, cerebral cortex, and cerebellum) was significantly lower in methamphetamine abusers than in control subjects, and this reduction was significantly inversely correlated with the duration of methamphetamine use. Furthermore, statistical parametric mapping analyses indicated that the density in the orbitofrontal, temporal, and anterior cingulate areas was closely associated with the magnitude of aggression in methamphetamine abusers. Protracted abuse of methamphetamine may reduce the density of the serotonin transporter in the brain, leading to elevated aggression, even in currently abstinent abusers.

  7. Research advances made in the avian brain and their relevance to poultry scientists.

    PubMed

    Kuenzel, Wayne J

    2014-12-01

    The year 2014 marked the tenth anniversary since the sequence of the chicken genome was published. Two other publications occurred during that time frame in different disciplines, and all 3 have affected poultry scientists. The purpose of this paper is to briefly review 2 publications that are better known to those in animal agriculture. The third paper will be addressed in more detail because it is one that many in poultry science probably have not read. The subject matter involves the avian brain and its future impact and is related to an announcement made by the president of the United States in April 2013. Due to the recent, rapid advances in the understanding of the vertebrate brain and behavior, a national goal was announced by President Obama to map the human brain in more detail than ever before to accelerate the understanding of brain function in health and disease. The main objective is to review the third paper published a decade ago to show that it laid the foundation for the chicken and other avian species to serve as relevant animal models to advance the understanding of the human brain. Emphasis will be placed on the forebrain. The overall goal is to show that the brain of birds is not that different from the mammalian brain and therefore can serve as an excellent comparative biomodel to understand fundamental principles of brain structure and function. ©2014 Poultry Science Association Inc.

  8. Mapping connectivity damage in the case of Phineas Gage.

    PubMed

    Van Horn, John Darrell; Irimia, Andrei; Torgerson, Carinna M; Chambers, Micah C; Kikinis, Ron; Toga, Arthur W

    2012-01-01

    White matter (WM) mapping of the human brain using neuroimaging techniques has gained considerable interest in the neuroscience community. Using diffusion weighted (DWI) and magnetic resonance imaging (MRI), WM fiber pathways between brain regions may be systematically assessed to make inferences concerning their role in normal brain function, influence on behavior, as well as concerning the consequences of network-level brain damage. In this paper, we investigate the detailed connectomics in a noted example of severe traumatic brain injury (TBI) which has proved important to and controversial in the history of neuroscience. We model the WM damage in the notable case of Phineas P. Gage, in whom a "tamping iron" was accidentally shot through his skull and brain, resulting in profound behavioral changes. The specific effects of this injury on Mr. Gage's WM connectivity have not previously been considered in detail. Using computed tomography (CT) image data of the Gage skull in conjunction with modern anatomical MRI and diffusion imaging data obtained in contemporary right handed male subjects (aged 25-36), we computationally simulate the passage of the iron through the skull on the basis of reported and observed skull fiducial landmarks and assess the extent of cortical gray matter (GM) and WM damage. Specifically, we find that while considerable damage was, indeed, localized to the left frontal cortex, the impact on measures of network connectedness between directly affected and other brain areas was profound, widespread, and a probable contributor to both the reported acute as well as long-term behavioral changes. Yet, while significantly affecting several likely network hubs, damage to Mr. Gage's WM network may not have been more severe than expected from that of a similarly sized "average" brain lesion. These results provide new insight into the remarkable brain injury experienced by this noteworthy patient.

  9. Group search algorithm recovers effective connectivity maps for individuals in homogeneous and heterogeneous samples.

    PubMed

    Gates, Kathleen M; Molenaar, Peter C M

    2012-10-15

    At its best, connectivity mapping can offer researchers great insight into how spatially disparate regions of the human brain coordinate activity during brain processing. A recent investigation conducted by Smith and colleagues (2011) on methods for estimating connectivity maps suggested that those which attempt to ascertain the direction of influence among ROIs rarely provide reliable results. Another problem gaining increasing attention is heterogeneity in connectivity maps. Most group-level methods require that the data come from homogeneous samples, and misleading findings may arise from current methods if the connectivity maps for individuals vary across the sample (which is likely the case). The utility of maps resulting from effective connectivity on the individual or group levels is thus diminished because they do not accurately inform researchers. The present paper introduces a novel estimation technique for fMRI researchers, Group Iterative Multiple Model Estimation (GIMME), which demonstrates that using information across individuals assists in the recovery of the existence of connections among ROIs used by Smith and colleagues (2011) and the direction of the influence. Using heterogeneous in-house data, we demonstrate that GIMME offers a unique improvement over current approaches by arriving at reliable group and individual structures even when the data are highly heterogeneous across individuals comprising the group. An added benefit of GIMME is that it obtains reliable connectivity map estimates equally well using the data from resting state, block, or event-related designs. GIMME provides researchers with a powerful, flexible tool for identifying directed connectivity maps at the group and individual levels. Copyright © 2012 Elsevier Inc. All rights reserved.

  10. Non-invasive Imaging based Detection and Mapping of Brain Oxidative Stress and its Correlation with Cognitive Functions

    DTIC Science & Technology

    2017-05-14

    AFRL-AFOSR-JP-TR-2017-0052 Non-invasive Imaging based Detection and Mapping of Brain Oxidative Stress and its Correlation with Cognative Functions...invasive Imaging based Detection and Mapping of Brain Oxidative Stress and its Correlation with Cognative Functions 5a.  CONTRACT NUMBER 5b.  GRANT...SUPPLEMENTARY NOTES 14. ABSTRACT Brain stress level measurement (non-invasively) in quantitative term is very helpful to correlate with various

  11. Non invasive Imaging based Detection and Mapping of Brain Oxidative Stress and its Correlation with Cognative Functions

    DTIC Science & Technology

    2017-05-14

    AFRL-AFOSR-JP-TR-2017-0052 Non-invasive Imaging based Detection and Mapping of Brain Oxidative Stress and its Correlation with Cognative Functions...invasive Imaging based Detection and Mapping of Brain Oxidative Stress and its Correlation with Cognative Functions 5a.  CONTRACT NUMBER 5b.  GRANT...SUPPLEMENTARY NOTES 14. ABSTRACT Brain stress level measurement (non-invasively) in quantitative term is very helpful to correlate with various

  12. Distributed neural system for emotional intelligence revealed by lesion mapping.

    PubMed

    Barbey, Aron K; Colom, Roberto; Grafman, Jordan

    2014-03-01

    Cognitive neuroscience has made considerable progress in understanding the neural architecture of human intelligence, identifying a broadly distributed network of frontal and parietal regions that support goal-directed, intelligent behavior. However, the contributions of this network to social and emotional aspects of intellectual function remain to be well characterized. Here we investigated the neural basis of emotional intelligence in 152 patients with focal brain injuries using voxel-based lesion-symptom mapping. Latent variable modeling was applied to obtain measures of emotional intelligence, general intelligence and personality from the Mayer, Salovey, Caruso Emotional Intelligence Test (MSCEIT), the Wechsler Adult Intelligence Scale and the Neuroticism-Extroversion-Openness Inventory, respectively. Regression analyses revealed that latent scores for measures of general intelligence and personality reliably predicted latent scores for emotional intelligence. Lesion mapping results further indicated that these convergent processes depend on a shared network of frontal, temporal and parietal brain regions. The results support an integrative framework for understanding the architecture of executive, social and emotional processes and make specific recommendations for the interpretation and application of the MSCEIT to the study of emotional intelligence in health and disease.

  13. Distributed neural system for emotional intelligence revealed by lesion mapping

    PubMed Central

    Colom, Roberto; Grafman, Jordan

    2014-01-01

    Cognitive neuroscience has made considerable progress in understanding the neural architecture of human intelligence, identifying a broadly distributed network of frontal and parietal regions that support goal-directed, intelligent behavior. However, the contributions of this network to social and emotional aspects of intellectual function remain to be well characterized. Here we investigated the neural basis of emotional intelligence in 152 patients with focal brain injuries using voxel-based lesion-symptom mapping. Latent variable modeling was applied to obtain measures of emotional intelligence, general intelligence and personality from the Mayer, Salovey, Caruso Emotional Intelligence Test (MSCEIT), the Wechsler Adult Intelligence Scale and the Neuroticism-Extroversion-Openness Inventory, respectively. Regression analyses revealed that latent scores for measures of general intelligence and personality reliably predicted latent scores for emotional intelligence. Lesion mapping results further indicated that these convergent processes depend on a shared network of frontal, temporal and parietal brain regions. The results support an integrative framework for understanding the architecture of executive, social and emotional processes and make specific recommendations for the interpretation and application of the MSCEIT to the study of emotional intelligence in health and disease. PMID:23171618

  14. Applying Cognitive Psychology to User Interfaces

    NASA Astrophysics Data System (ADS)

    Durrani, Sabeen; Durrani, Qaiser S.

    This paper explores some key aspects of cognitive psychology that may be mapped onto user interfaces. Major focus in existing user interface guidelines is on consistency, simplicity, feedback, system messages, display issues, navigation, colors, graphics, visibility and error prevention [8-10]. These guidelines are effective indesigning user interfaces. However, these guidelines do not handle the issues that may arise due to the innate structure of human brain and human limitations. For example, where to place graphics on the screen so that user can easily process them and what kind of background should be given on the screen according to the limitation of human motor system. In this paper we have collected some available guidelines from the area of cognitive psychology [1, 5, 7]. In addition, we have extracted few guidelines from theories and studies of cognitive psychology [3, 11] which may be mapped to user interfaces.

  15. The brain finger protein gene (ZNF179), a member of the RING finger family, maps within the Smith-Magenis syndrome region at 17p11.2

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

    Kimura, Toshiyuki; Arakawa, Yoshiki; Inazawa, Johji

    1997-03-31

    Smith-Magenis syndrome (SAIS) is caused by a microdeletion of 17p11.2 and comprises developmental and growth delay, facial abnormalities, unusual behavior and sleep problems. This phenotype may be due to haploinsufficiency of several contiguous genes. The human brain finger protein gene (ZNF179), a member of the RING finger protein family, has been isolated and mapped to l7p11.2. FISH analyses of metaphase or interphase chromosomes of 6 patients with SMS show that ZNF179 was deleted in one of the 2 homologs (17p11.2), indicating a possible association of the defect of this gene with the pathogenesis of SMS. Furthermore, using a prophase FISHmore » ordering system, we sublocalized ZNF179 proximally to LLGL which lies on the critical region for SMS. 27 refs., 2 figs.« less

  16. [Right extremities pain caused by a malacia lesion in the left putamen:a resting functional magnetic resonance imaging of the marginal division of the human brain].

    PubMed

    Chen, Zhi-Ye; Ma, Lin

    2014-04-01

    To explore the role of marginal division of the human brain in the pain modulation. Resting functional magnetic resonance imaging was applied in a patient with right extremities pain caused by a malacia lesion in the left putamen and in 8 healthy volunteers. Marginal division was defined using manual drawing on structure images, and was applied to the computation of fuctional connectivity maps. The functional connectivities in the left marginal division showed an evident decrease in the patient when compared with healthy controls. These connectivities were mainly located in the bilateral head of caudate nucleus, putamen, and left globus pallidus. The marginal division may be involved in the pain modulation.

  17. Dissociable meta-analytic brain networks contribute to coordinated emotional processing.

    PubMed

    Riedel, Michael C; Yanes, Julio A; Ray, Kimberly L; Eickhoff, Simon B; Fox, Peter T; Sutherland, Matthew T; Laird, Angela R

    2018-06-01

    Meta-analytic techniques for mining the neuroimaging literature continue to exert an impact on our conceptualization of functional brain networks contributing to human emotion and cognition. Traditional theories regarding the neurobiological substrates contributing to affective processing are shifting from regional- towards more network-based heuristic frameworks. To elucidate differential brain network involvement linked to distinct aspects of emotion processing, we applied an emergent meta-analytic clustering approach to the extensive body of affective neuroimaging results archived in the BrainMap database. Specifically, we performed hierarchical clustering on the modeled activation maps from 1,747 experiments in the affective processing domain, resulting in five meta-analytic groupings of experiments demonstrating whole-brain recruitment. Behavioral inference analyses conducted for each of these groupings suggested dissociable networks supporting: (1) visual perception within primary and associative visual cortices, (2) auditory perception within primary auditory cortices, (3) attention to emotionally salient information within insular, anterior cingulate, and subcortical regions, (4) appraisal and prediction of emotional events within medial prefrontal and posterior cingulate cortices, and (5) induction of emotional responses within amygdala and fusiform gyri. These meta-analytic outcomes are consistent with a contemporary psychological model of affective processing in which emotionally salient information from perceived stimuli are integrated with previous experiences to engender a subjective affective response. This study highlights the utility of using emergent meta-analytic methods to inform and extend psychological theories and suggests that emotions are manifest as the eventual consequence of interactions between large-scale brain networks. © 2018 Wiley Periodicals, Inc.

  18. Brain maps 4.0—Structure of the rat brain: An open access atlas with global nervous system nomenclature ontology and flatmaps

    PubMed Central

    2018-01-01

    Abstract The fourth edition (following editions in 1992, 1998, 2004) of Brain maps: structure of the rat brain is presented here as an open access internet resource for the neuroscience community. One new feature is a set of 10 hierarchical nomenclature tables that define and describe all parts of the rat nervous system within the framework of a strictly topographic system devised previously for the human nervous system. These tables constitute a global ontology for knowledge management systems dealing with neural circuitry. A second new feature is an aligned atlas of bilateral flatmaps illustrating rat nervous system development from the neural plate stage to the adult stage, where most gray matter regions, white matter tracts, ganglia, and nerves listed in the nomenclature tables are illustrated schematically. These flatmaps are convenient for future development of online applications analogous to “Google Maps” for systems neuroscience. The third new feature is a completely revised Atlas of the rat brain in spatially aligned transverse sections that can serve as a framework for 3‐D modeling. Atlas parcellation is little changed from the preceding edition, but the nomenclature for rat is now aligned with an emerging panmammalian neuroanatomical nomenclature. All figures are presented in Adobe Illustrator vector graphics format that can be manipulated, modified, and resized as desired, and freely used with a Creative Commons license. PMID:29277900

  19. Mapping Language Problems in the Brain

    MedlinePlus

    ... issue Health Capsule Mapping Language Problems in the Brain En español Send us your comments We often ... more about how language is organized in the brain, an NIH-funded research team studied people with ...

  20. The brain, self and society: a social-neuroscience model of predictive processing.

    PubMed

    Kelly, Michael P; Kriznik, Natasha M; Kinmonth, Ann Louise; Fletcher, Paul C

    2018-05-10

    This paper presents a hypothesis about how social interactions shape and influence predictive processing in the brain. The paper integrates concepts from neuroscience and sociology where a gulf presently exists between the ways that each describe the same phenomenon - how the social world is engaged with by thinking humans. We combine the concepts of predictive processing models (also called predictive coding models in the neuroscience literature) with ideal types, typifications and social practice - concepts from the sociological literature. This generates a unified hypothetical framework integrating the social world and hypothesised brain processes. The hypothesis combines aspects of neuroscience and psychology with social theory to show how social behaviors may be "mapped" onto brain processes. It outlines a conceptual framework that connects the two disciplines and that may enable creative dialogue and potential future research.

  1. 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

  2. Using Brain Electrical Activity Mapping to Diagnose Learning Disabilities.

    ERIC Educational Resources Information Center

    Torello, Michael, W.; Duffy, Frank H.

    1985-01-01

    Cognitive neuroscience assumes that measurement of brain electrical activity should relate to cognition. Brain Electrical Activity Mapping (BEAM), a non-invasive technique, is used to record changes in activity from one brain area to another and is 80 to 90 percent successful in classifying subjects as dyslexic or normal. (MT)

  3. Anatomo-clinical overlapping maps (AnaCOM): a new method to create anatomo-functional maps from neuropsychological tests and structural MRI scan of subjects with brain lesions

    NASA Astrophysics Data System (ADS)

    Kinkingnehun, Serge R. J.; du Boisgueheneuc, Foucaud; Golmard, Jean-Louis; Zhang, Sandy X.; Levy, Richard; Dubois, Bruno

    2004-04-01

    We have developed a new technique to analyze correlations between brain anatomy and its neurological functions. The technique is based on the anatomic MRI of patients with brain lesions who are administered neuropsychological tests. Brain lesions of the MRI scans are first manually segmented. The MRI volumes are then normalized to a reference map, using the segmented area as a mask. After normalization, the brain lesions of the MRI are segmented again in order to redefine the border of the lesions in the context of the normalized brain. Once the MRI is segmented, the patient's score on the neuropsychological test is assigned to each voxel in the lesioned area, while the rest of the voxels of the image are set to 0. Subsequently, the individual patient's MRI images are superimposed, and each voxel is reassigned the average score of the patients who have a lesion at that voxel. A threshold is applied to remove regions having less than three overlaps. This process leads to an anatomo-functional map that links brain areas to functional loss. Other maps can be created to aid in analyzing the functional maps, such as one that indicates the 95% confidence interval of the averaged scores for each area. This anatomo-clinical overlapping map (AnaCOM) method was used to obtain functional maps from patients with lesions in the superior frontal gyrus. By finding particular subregions more responsible for a particular deficit, this method can generate new hypotheses to be tested by conventional group methods.

  4. Not single brain areas but a network is involved in language: Applications in presurgical planning.

    PubMed

    Alemi, Razieh; Batouli, Seyed Amir Hossein; Behzad, Ebrahim; Ebrahimpoor, Mitra; Oghabian, Mohammad Ali

    2018-02-01

    Language is an important human function, and is a determinant of the quality of life. In conditions such as brain lesions, disruption of the language function may occur, and lesion resection is a solution for that. Presurgical planning to determine the language-related brain areas would enhance the chances of language preservation after the operation; however, availability of a normative language template is essential. In this study, using data from 60 young individuals who were meticulously checked for mental and physical health, and using fMRI and robust imaging and data analysis methods, functional brain maps for the language production, perception and semantic were produced. The obtained templates showed that the language function should be considered as the product of the collaboration of a network of brain regions, instead of considering only few brain areas to be involved in that. This study has important clinical applications, and extends our knowledge on the neuroanatomy of the language function. Copyright © 2018 Elsevier B.V. All rights reserved.

  5. Delineation of early brain development from fetuses to infants with diffusion MRI and beyond.

    PubMed

    Ouyang, Minhui; Dubois, Jessica; Yu, Qinlin; Mukherjee, Pratik; Huang, Hao

    2018-04-12

    Dynamic macrostructural and microstructural changes take place from the mid-fetal stage to 2 years after birth. Delineating structural changes of the brain during early development provides new insights into the complicated processes of both typical development and the pathological mechanisms underlying various psychiatric and neurological disorders including autism, attention deficit hyperactivity disorder and schizophrenia. Decades of histological studies have identified strong spatial and functional maturation gradients in human brain gray and white matter. The recent improvements in magnetic resonance imaging (MRI) techniques, especially diffusion MRI (dMRI), relaxometry imaging, and magnetization transfer imaging (MTI) have provided unprecedented opportunities to non-invasively quantify and map the early developmental changes at whole brain and regional levels. Here, we review the recent advances in understanding early brain structural development during the second half of gestation and the first two postnatal years using modern MR techniques. Specifically, we review studies that delineate the emergence and microstructural maturation of white matter tracts, as well as dynamic mapping of inhomogeneous cortical microstructural organization unique to fetuses and infants. These imaging studies converge into maturational curves of MRI measurements that are distinctive across different white matter tracts and cortical regions. Furthermore, contemporary models offering biophysical interpretations of the dMRI-derived measurements are illustrated to infer the underlying microstructural changes. Collectively, this review summarizes findings that contribute to charting spatiotemporally heterogeneous gray and white matter structural development, offering MRI-based biomarkers of typical brain development and setting the stage for understanding aberrant brain development in neurodevelopmental disorders. Copyright © 2018 Elsevier Inc. All rights reserved.

  6. Formal Models of the Network Co-occurrence Underlying Mental Operations.

    PubMed

    Bzdok, Danilo; Varoquaux, Gaël; Grisel, Olivier; Eickenberg, Michael; Poupon, Cyril; Thirion, Bertrand

    2016-06-01

    Systems neuroscience has identified a set of canonical large-scale networks in humans. These have predominantly been characterized by resting-state analyses of the task-unconstrained, mind-wandering brain. Their explicit relationship to defined task performance is largely unknown and remains challenging. The present work contributes a multivariate statistical learning approach that can extract the major brain networks and quantify their configuration during various psychological tasks. The method is validated in two extensive datasets (n = 500 and n = 81) by model-based generation of synthetic activity maps from recombination of shared network topographies. To study a use case, we formally revisited the poorly understood difference between neural activity underlying idling versus goal-directed behavior. We demonstrate that task-specific neural activity patterns can be explained by plausible combinations of resting-state networks. The possibility of decomposing a mental task into the relative contributions of major brain networks, the "network co-occurrence architecture" of a given task, opens an alternative access to the neural substrates of human cognition.

  7. Formal Models of the Network Co-occurrence Underlying Mental Operations

    PubMed Central

    Bzdok, Danilo; Varoquaux, Gaël; Grisel, Olivier; Eickenberg, Michael; Poupon, Cyril; Thirion, Bertrand

    2016-01-01

    Systems neuroscience has identified a set of canonical large-scale networks in humans. These have predominantly been characterized by resting-state analyses of the task-unconstrained, mind-wandering brain. Their explicit relationship to defined task performance is largely unknown and remains challenging. The present work contributes a multivariate statistical learning approach that can extract the major brain networks and quantify their configuration during various psychological tasks. The method is validated in two extensive datasets (n = 500 and n = 81) by model-based generation of synthetic activity maps from recombination of shared network topographies. To study a use case, we formally revisited the poorly understood difference between neural activity underlying idling versus goal-directed behavior. We demonstrate that task-specific neural activity patterns can be explained by plausible combinations of resting-state networks. The possibility of decomposing a mental task into the relative contributions of major brain networks, the "network co-occurrence architecture" of a given task, opens an alternative access to the neural substrates of human cognition. PMID:27310288

  8. Altruistic behavior: mapping responses in the brain

    PubMed Central

    Filkowski, Megan M; Cochran, R Nick; Haas, Brian W

    2016-01-01

    Altruism is an important social construct related to human relationships and the way many interpersonal and economic decisions are made. Recent progress in social neuroscience research shows that altruism is associated with a specific pattern of brain activity. The tendency to engage in altruistic behaviors is associated with greater activity within limbic regions such as the nucleus accumbens and anterior cingulate cortex in addition to cortical regions such as the medial prefrontal cortex and temporoparietal junction. Here, we review existing theoretical models of altruism as well as recent empirical neuroimaging research demonstrating how altruism is processed within the brain. This review not only highlights the progress in neuroscience research on altruism but also shows that there exist several open questions that remain unexplored. PMID:28580317

  9. Improved Determination of the Myelin Water Fraction in Human Brain using Magnetic Resonance Imaging through Bayesian Analysis of mcDESPOT

    PubMed Central

    Bouhrara, Mustapha; Spencer, Richard G.

    2015-01-01

    Myelin water fraction (MWF) mapping with magnetic resonance imaging has led to the ability to directly observe myelination and demyelination in both the developing brain and in disease. Multicomponent driven equilibrium single pulse observation of T1 and T2 (mcDESPOT) has been proposed as a rapid approach for multicomponent relaxometry and has been applied to map MWF in human brain. However, even for the simplest two-pool signal model consisting of MWF and non-myelin-associated water, the dimensionality of the parameter space for obtaining MWF estimates remains high. This renders parameter estimation difficult, especially at low-to-moderate signal-to-noise ratios (SNR), due to the presence of local minima and the flatness of the fit residual energy surface used for parameter determination using conventional nonlinear least squares (NLLS)-based algorithms. In this study, we introduce three Bayesian approaches for analysis of the mcDESPOT signal model to determine MWF. Given the high dimensional nature of mcDESPOT signal model, and, thereby, the high dimensional marginalizations over nuisance parameters needed to derive the posterior probability distribution of MWF parameter, the introduced Bayesian analyses use different approaches to reduce the dimensionality of the parameter space. The first approach uses normalization by average signal amplitude, and assumes that noise can be accurately estimated from signal-free regions of the image. The second approach likewise uses average amplitude normalization, but incorporates a full treatment of noise as an unknown variable through marginalization. The third approach does not use amplitude normalization and incorporates marginalization over both noise and signal amplitude. Through extensive Monte Carlo numerical simulations and analysis of in-vivo human brain datasets exhibiting a range of SNR and spatial resolution, we demonstrated the markedly improved accuracy and precision in the estimation of MWF using these Bayesian methods as compared to the stochastic region contraction (SRC) implementation of NLLS. PMID:26499810

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

    Savukoski, M.; Peltonen, L.; Santavuori, P.

    We demonstrate here that at least four genetically separate loci are involved in the pathogenesis of human neuronal ceroid lipofuscinoses (NCLs), fatal brain disorders of children. Earlier the assignments of the infantile and juvenile subtypes of NCL to 1p32 and 16p12 had revealed two loci; and here a variant subtype of the late-infantile form of NCL is mapped to a well-defined region on 13q21.1-q32, whereas the clinically similar, classical form of late-infantile NCL was found to represent the fourth, yet-unidentified NCL locus. The linkage disequilibrium was crucial for locus assignment in our highly limited family material, and the data exemplifymore » the significance of this phenomenon in the random mapping of rare human diseases. 22 refs., 4 figs., 3 tabs.« less

  11. Exploring sex differences in the adult zebra finch brain: In vivo diffusion tensor imaging and ex vivo super-resolution track density imaging.

    PubMed

    Hamaide, Julie; De Groof, Geert; Van Steenkiste, Gwendolyn; Jeurissen, Ben; Van Audekerke, Johan; Naeyaert, Maarten; Van Ruijssevelt, Lisbeth; Cornil, Charlotte; Sijbers, Jan; Verhoye, Marleen; Van der Linden, Annemie

    2017-02-01

    Zebra finches are an excellent model to study the process of vocal learning, a complex socially-learned tool of communication that forms the basis of spoken human language. So far, structural investigation of the zebra finch brain has been performed ex vivo using invasive methods such as histology. These methods are highly specific, however, they strongly interfere with performing whole-brain analyses and exclude longitudinal studies aimed at establishing causal correlations between neuroplastic events and specific behavioral performances. Therefore, the aim of the current study was to implement an in vivo Diffusion Tensor Imaging (DTI) protocol sensitive enough to detect structural sex differences in the adult zebra finch brain. Voxel-wise comparison of male and female DTI parameter maps shows clear differences in several components of the song control system (i.e. Area X surroundings, the high vocal center (HVC) and the lateral magnocellular nucleus of the anterior nidopallium (LMAN)), which corroborate previous findings and are in line with the clear behavioral difference as only males sing. Furthermore, to obtain additional insights into the 3-dimensional organization of the zebra finch brain and clarify findings obtained by the in vivo study, ex vivo DTI data of the male and female brain were acquired as well, using a recently established super-resolution reconstruction (SRR) imaging strategy. Interestingly, the SRR-DTI approach led to a marked reduction in acquisition time without interfering with the (spatial and angular) resolution and SNR which enabled to acquire a data set characterized by a 78μm isotropic resolution including 90 diffusion gradient directions within 44h of scanning time. Based on the reconstructed SRR-DTI maps, whole brain probabilistic Track Density Imaging (TDI) was performed for the purpose of super resolved track density imaging, further pushing the resolution up to 40μm isotropic. The DTI and TDI maps realized atlas-quality anatomical maps that enable a clear delineation of most components of the song control and auditory systems. In conclusion, this study paves the way for longitudinal in vivo and high-resolution ex vivo experiments aimed at disentangling neuroplastic events that characterize the critical period for vocal learning in zebra finch ontogeny. Copyright © 2016 Elsevier Inc. All rights reserved.

  12. Quantile rank maps: a new tool for understanding individual brain development.

    PubMed

    Chen, Huaihou; Kelly, Clare; Castellanos, F Xavier; He, Ye; Zuo, Xi-Nian; Reiss, Philip T

    2015-05-01

    We propose a novel method for neurodevelopmental brain mapping that displays how an individual's values for a quantity of interest compare with age-specific norms. By estimating smoothly age-varying distributions at a set of brain regions of interest, we derive age-dependent region-wise quantile ranks for a given individual, which can be presented in the form of a brain map. Such quantile rank maps could potentially be used for clinical screening. Bootstrap-based confidence intervals are proposed for the quantile rank estimates. We also propose a recalibrated Kolmogorov-Smirnov test for detecting group differences in the age-varying distribution. This test is shown to be more robust to model misspecification than a linear regression-based test. The proposed methods are applied to brain imaging data from the Nathan Kline Institute Rockland Sample and from the Autism Brain Imaging Data Exchange (ABIDE) sample. Copyright © 2015 Elsevier Inc. All rights reserved.

  13. Optogenetic mapping of brain circuitry

    NASA Astrophysics Data System (ADS)

    Augustine, George J.; Berglund, Ken; Gill, Harin; Hoffmann, Carolin; Katarya, Malvika; Kim, Jinsook; Kudolo, John; Lee, Li M.; Lee, Molly; Lo, Daniel; Nakajima, Ryuichi; Park, Min Yoon; Tan, Gregory; Tang, Yanxia; Teo, Peggy; Tsuda, Sachiko; Wen, Lei; Yoon, Su-In

    2012-10-01

    Studies of the brain promise to be revolutionized by new experimental strategies that harness the combined power of optical techniques and genetics. We have mapped the circuitry of the mouse brain by using both optogenetic actuators that control neuronal activity and optogenetic sensors that detect neuronal activity. Using the light-activated cation channel, channelrhodopsin-2, to locally photostimulate neurons allows high-speed mapping of local and long-range circuitry. For example, with this approach we have mapped local circuits in the cerebral cortex, cerebellum and many other brain regions. Using the fluorescent sensor for chloride ions, Clomeleon, allows imaging of the spatial and temporal dimensions of inhibitory circuits in the brain. This approach allows imaging of both conventional "phasic" synaptic inhibition as well as unconventional "tonic" inhibition. The combined use of light to both control and monitor neural activity creates unprecedented opportunities to explore brain function, screen pharmaceutical agents, and potentially to use light to ameliorate psychiatric and neurological disorders.

  14. Fast Mapping of Novel Word Forms Traced Neurophysiologically

    PubMed Central

    Shtyrov, Yury

    2011-01-01

    Human capacity to quickly learn new words, critical for our ability to communicate using language, is well-known from behavioral studies and observations, but its neural underpinnings remain unclear. In this study, we have used event-related potentials to record brain activity to novel spoken word forms as they are being learnt by the human nervous system through passive auditory exposure. We found that the brain response dynamics change dramatically within the short (20 min) exposure session: as the subjects become familiarized with the novel word forms, the early (∼100 ms) fronto-central activity they elicit increases in magnitude and becomes similar to that of known real words. At the same time, acoustically similar real words used as control stimuli show a relatively stable response throughout the recording session; these differences between the stimulus groups are confirmed using both factorial and linear regression analyses. Furthermore, acoustically matched novel non-speech stimuli do not demonstrate similar response increase, suggesting neural specificity of this rapid learning phenomenon to linguistic stimuli. Left-lateralized perisylvian cortical networks appear to be underlying such fast mapping of novel word forms unto the brain’s mental lexicon. PMID:22125543

  15. Algebraic Topology of Multi-Brain Connectivity Networks Reveals Dissimilarity in Functional Patterns during Spoken Communications

    PubMed Central

    Tadić, Bosiljka; Andjelković, Miroslav; Boshkoska, Biljana Mileva; Levnajić, Zoran

    2016-01-01

    Human behaviour in various circumstances mirrors the corresponding brain connectivity patterns, which are suitably represented by functional brain networks. While the objective analysis of these networks by graph theory tools deepened our understanding of brain functions, the multi-brain structures and connections underlying human social behaviour remain largely unexplored. In this study, we analyse the aggregate graph that maps coordination of EEG signals previously recorded during spoken communications in two groups of six listeners and two speakers. Applying an innovative approach based on the algebraic topology of graphs, we analyse higher-order topological complexes consisting of mutually interwoven cliques of a high order to which the identified functional connections organise. Our results reveal that the topological quantifiers provide new suitable measures for differences in the brain activity patterns and inter-brain synchronisation between speakers and listeners. Moreover, the higher topological complexity correlates with the listener’s concentration to the story, confirmed by self-rating, and closeness to the speaker’s brain activity pattern, which is measured by network-to-network distance. The connectivity structures of the frontal and parietal lobe consistently constitute distinct clusters, which extend across the listener’s group. Formally, the topology quantifiers of the multi-brain communities exceed the sum of those of the participating individuals and also reflect the listener’s rated attributes of the speaker and the narrated subject. In the broader context, the presented study exposes the relevance of higher topological structures (besides standard graph measures) for characterising functional brain networks under different stimuli. PMID:27880802

  16. Methamphetamine- and Trauma-Induced Brain Injuries: Comparative Cellular and Molecular Neurobiological Substrates

    PubMed Central

    Gold, Mark S.; Kobeissy, Firas H.; Wang, Kevin K.W.; Merlo, Lisa J.; Bruijnzeel, Adriaan W.; Krasnova, Irina N.; Cadet, Jean Lud

    2009-01-01

    The use of methamphetamine (METH) is a growing public health problem because its abuse is associated with long-term biochemical and structural effects on the human brain. Neurodegeneration is often observed in humans as a result of mechanical injuries (e.g. traumatic brain injury, TBI) and ischemic damage (strokes). In this review, we discuss recent findings documenting the fact that the psychostimulant drug, METH, can cause neuronal damage in several brain regions. The accumulated evidence from our laboratories and those of other investigators indicates that acute administration of METH leads to activation of calpain and caspase proteolytic systems. These systems are also involved in causing neuronal damage secondary to traumatic and ischemic brain injuries. Protease activation is accompanied by proteolysis of endogenous neuronal structural proteins (αII-spectrin and MAP-tau protein) evidenced by the appearance of their breakdown products after these injuries. When taken together, these observations suggest that METH exposure, like TBI, can cause substantial damage to the brain by causing both apoptotic and necrotic cell death in the brains of METH addicts who use large doses of the drug during their lifetimes. Finally, because METH abuse is accompanied by functional and structural changes in the brain similar to those in TBI, METH addicts might experience greater benefit if their treatment involved greater emphasis on rehabilitation in conjunction with the use of potential neuroprotective pharmacological agents such as calpain and caspase inhibitors similar to those used in TBI. PMID:19345341

  17. Cortical fibers orientation mapping using in-vivo whole brain 7 T diffusion MRI.

    PubMed

    Gulban, Omer F; De Martino, Federico; Vu, An T; Yacoub, Essa; Uğurbil, Kamil; Lenglet, Christophe

    2018-05-10

    Diffusion MRI of the cortical gray matter is challenging because the micro-environment probed by water molecules is much more complex than within the white matter. High spatial and angular resolutions are therefore necessary to uncover anisotropic diffusion patterns and laminar structures, which provide complementary (e.g. to anatomical and functional MRI) microstructural information about the cortex architectonic. Several ex-vivo and in-vivo MRI studies have recently addressed this question, however predominantly with an emphasis on specific cortical areas. There is currently no whole brain in-vivo data leveraging multi-shell diffusion MRI acquisition at high spatial resolution, and depth dependent analysis, to characterize the complex organization of cortical fibers. Here, we present unique in-vivo human 7T diffusion MRI data, and a dedicated cortical depth dependent analysis pipeline. We leverage the high spatial (1.05 mm isotropic) and angular (198 diffusion gradient directions) resolution of this whole brain dataset to improve cortical fiber orientations mapping, and study neurites (axons and/or dendrites) trajectories across cortical depths. Tangential fibers in superficial cortical depths and crossing fiber configurations in deep cortical depths are identified. Fibers gradually inserting into the gyral walls are visualized, which contributes to mitigating the gyral bias effect. Quantitative radiality maps and histograms in individual subjects and cortex-based aligned datasets further support our results. Copyright © 2018 Elsevier Inc. All rights reserved.

  18. Music Listening modulates Functional Connectivity and Information Flow in the Human Brain.

    PubMed

    Karmonik, Christof; Brandt, Anthony; Anderson, Jeff; Brooks, Forrest; Lytle, Julie; Silverman, Elliott; Frazier, Jeff T

    2016-07-27

    Listening to familiar music has recently been reported to be beneficial during recovery from stroke. A better understanding of changes in functional connectivity and information flow is warranted in order to further optimize and target this approach through music therapy. Twelve healthy volunteers listened to seven different auditory samples during an fMRI scanning session: a musical piece chosen by the volunteer that evokes a strong emotional response (referred to as: "self-selected emotional"), two unfamiliar music pieces (Invention #1 by J. S. Bach* and Gagaku - Japanese classical opera, referred to as "unfamiliar"), the Bach piece repeated with visual guidance (DML: Directed Music Listening) and three spoken language pieces (unfamiliar African click language, an excerpt of emotionally charged language, and an unemotional reading of a news bulletin). Functional connectivity and betweenness (BTW) maps, a measure for information flow, were created with a graph-theoretical approach. Distinct variation in functional connectivity was found for different music pieces consistently for all subjects. Largest brain areas were recruited for processing self-selected music with emotional attachment or culturally unfamiliar music. Maps of information flow correlated significantly with fMRI BOLD activation maps (p<0.05). Observed differences in BOLD activation and functional connectivity may help explain previously observed beneficial effects in stroke recovery, as increased blood flow to damaged brain areas stimulated by active engagement through music listening may have supported a state more conducive to therapy.

  19. Identification and characterization of a novel serine-threonine kinase gene from the Xp22 region.

    PubMed

    Montini, E; Andolfi, G; Caruso, A; Buchner, G; Walpole, S M; Mariani, M; Consalez, G; Trump, D; Ballabio, A; Franco, B

    1998-08-01

    Eukaryotic protein kinases are part of a large and expanding family of proteins. Through our transcriptional mapping effort in the Xp22 region, we have isolated and sequenced the full-length transcript of STK9, a novel cDNA highly homologous to serine-threonine kinases. A number of human genetic disorders have been mapped to the region where STK9 has been localized including Nance-Horan (NH) syndrome, oral-facial-digital syndrome type 1 (OFD1), and a novel locus for nonsyndromic sensorineural deafness (DFN6). To evaluate the possible involvement of STK9 in any of the above-mentioned disorders, a 2416-bp full-length cDNA was assembled. The entire genomic structure of the gene, which is composed of 20 coding exons, was determined. Northern analysis revealed a transcript larger than 9.5 kb in several tissues including brain, lung, and kidney. The mouse homologue (Stk9) was identified and mapped in the mouse in the region syntenic to human Xp. This location is compatible with the location of the Xcat mutant, which shows congenital cataracts very similar to those observed in NH patients. Sequence homologies, expression pattern, and mapping information in both human and mouse make STK9 a candidate gene for the above-mentioned disorders. Copyright 1998 Academic Press.

  20. Low-resolution mapping of the effective attenuation coefficient of the human head: a multidistance approach applied to high-density optical recordings

    PubMed Central

    Chiarelli, Antonio M.; Maclin, Edward L.; Low, Kathy A.; Fantini, Sergio; Fabiani, Monica; Gratton, Gabriele

    2017-01-01

    Abstract. Near infrared (NIR) light has been widely used for measuring changes in hemoglobin concentration in the human brain (functional NIR spectroscopy, fNIRS). fNIRS is based on the differential measurement and estimation of absorption perturbations, which, in turn, are based on correctly estimating the absolute parameters of light propagation. To do so, it is essential to accurately characterize the baseline optical properties of tissue (absorption and reduced scattering coefficients). However, because of the diffusive properties of the medium, separate determination of absorption and scattering across the head is challenging. The effective attenuation coefficient (EAC), which is proportional to the geometric mean of absorption and reduced scattering coefficients, can be estimated in a simpler fashion by multidistance light decay measurements. EAC mapping could be of interest for the scientific community because of its absolute information content, and because light propagation is governed by the EAC for source–detector distances exceeding 1 cm, which sense depths extending beyond the scalp and skull layers. Here, we report an EAC mapping procedure that can be applied to standard fNIRS recordings, yielding topographic maps with 2- to 3-cm resolution. Application to human data indicates the importance of venous sinuses in determining regional EAC variations, a factor often overlooked. PMID:28466026

  1. Low-resolution mapping of the effective attenuation coefficient of the human head: a multidistance approach applied to high-density optical recordings.

    PubMed

    Chiarelli, Antonio M; Maclin, Edward L; Low, Kathy A; Fantini, Sergio; Fabiani, Monica; Gratton, Gabriele

    2017-04-01

    Near infrared (NIR) light has been widely used for measuring changes in hemoglobin concentration in the human brain (functional NIR spectroscopy, fNIRS). fNIRS is based on the differential measurement and estimation of absorption perturbations, which, in turn, are based on correctly estimating the absolute parameters of light propagation. To do so, it is essential to accurately characterize the baseline optical properties of tissue (absorption and reduced scattering coefficients). However, because of the diffusive properties of the medium, separate determination of absorption and scattering across the head is challenging. The effective attenuation coefficient (EAC), which is proportional to the geometric mean of absorption and reduced scattering coefficients, can be estimated in a simpler fashion by multidistance light decay measurements. EAC mapping could be of interest for the scientific community because of its absolute information content, and because light propagation is governed by the EAC for source-detector distances exceeding 1 cm, which sense depths extending beyond the scalp and skull layers. Here, we report an EAC mapping procedure that can be applied to standard fNIRS recordings, yielding topographic maps with 2- to 3-cm resolution. Application to human data indicates the importance of venous sinuses in determining regional EAC variations, a factor often overlooked.

  2. The influence of brain iron and myelin on magnetic susceptibility and effective transverse relaxation - A biochemical and histological validation study.

    PubMed

    Hametner, Simon; Endmayr, Verena; Deistung, Andreas; Palmrich, Pilar; Prihoda, Max; Haimburger, Evelin; Menard, Christian; Feng, Xiang; Haider, Thomas; Leisser, Marianne; Köck, Ulrike; Kaider, Alexandra; Höftberger, Romana; Robinson, Simon; Reichenbach, Jürgen R; Lassmann, Hans; Traxler, Hannes; Trattnig, Siegfried; Grabner, Günther

    2018-06-15

    Quantitative susceptibility mapping (QSM) and effective transverse relaxation rate (R2*) mapping are both highly sensitive to variations in brain iron content. Clinical Magnetic Resonance Imaging (MRI) studies report changes of susceptibilities and relaxation rates in various neurological diseases which are often equated with changes in regional brain iron content. However, these mentioned metrics lack specificity for iron, since they are also influenced by the presence of myelin. In this study, we assessed the extent to which QSM and R2* reflect iron concentration as well as histological iron and myelin intensities. Six unfixed human post-mortem brains were imaged in situ with a 7 T MRI scanner. After formalin fixation, the brains were sliced axially and punched. 671 tissue punches were subjected to ferrozine iron quantification. Subsequently, brain slices were embedded in paraffin, and histological double-hemispheric axial brain slices were stained for Luxol fast blue (myelin) and diaminobenzidine (DAB)-enhanced Turnbull blue (iron). 3331 regions of interest (ROIs) were drawn on the histological stainings to assess myelin and iron intensities, which were compared with MRI data in corresponding ROIs. QSM more closely reflected quantitative ferrozine iron values (r = 0.755 vs. 0.738), whereas R2* correlated better with iron staining intensities (r = 0.619 vs. 0.445). Myelin intensities correlated negatively with QSM (r = -0.352), indicating a diamagnetic effect of myelin on susceptibility. Myelin intensities were higher in the thalamus than in the basal ganglia. A significant relationship was nonetheless observed between quantitative iron values and QSM, confirming the applicability of the latter in this brain region for iron quantification. Copyright © 2018. Published by Elsevier Inc.

  3. Knowledge-Guided Robust MRI Brain Extraction for Diverse Large-Scale Neuroimaging Studies on Humans and Non-Human Primates

    PubMed Central

    Wang, Yaping; Nie, Jingxin; Yap, Pew-Thian; Li, Gang; Shi, Feng; Geng, Xiujuan; Guo, Lei; Shen, Dinggang

    2014-01-01

    Accurate and robust brain extraction is a critical step in most neuroimaging analysis pipelines. In particular, for the large-scale multi-site neuroimaging studies involving a significant number of subjects with diverse age and diagnostic groups, accurate and robust extraction of the brain automatically and consistently is highly desirable. In this paper, we introduce population-specific probability maps to guide the brain extraction of diverse subject groups, including both healthy and diseased adult human populations, both developing and aging human populations, as well as non-human primates. Specifically, the proposed method combines an atlas-based approach, for coarse skull-stripping, with a deformable-surface-based approach that is guided by local intensity information and population-specific prior information learned from a set of real brain images for more localized refinement. Comprehensive quantitative evaluations were performed on the diverse large-scale populations of ADNI dataset with over 800 subjects (55∼90 years of age, multi-site, various diagnosis groups), OASIS dataset with over 400 subjects (18∼96 years of age, wide age range, various diagnosis groups), and NIH pediatrics dataset with 150 subjects (5∼18 years of age, multi-site, wide age range as a complementary age group to the adult dataset). The results demonstrate that our method consistently yields the best overall results across almost the entire human life span, with only a single set of parameters. To demonstrate its capability to work on non-human primates, the proposed method is further evaluated using a rhesus macaque dataset with 20 subjects. Quantitative comparisons with popularly used state-of-the-art methods, including BET, Two-pass BET, BET-B, BSE, HWA, ROBEX and AFNI, demonstrate that the proposed method performs favorably with superior performance on all testing datasets, indicating its robustness and effectiveness. PMID:24489639

  4. Semi-automated quantification and neuroanatomical mapping of heterogeneous cell populations.

    PubMed

    Mendez, Oscar A; Potter, Colin J; Valdez, Michael; Bello, Thomas; Trouard, Theodore P; Koshy, Anita A

    2018-07-15

    Our group studies the interactions between cells of the brain and the neurotropic parasite Toxoplasma gondii. Using an in vivo system that allows us to permanently mark and identify brain cells injected with Toxoplasma protein, we have identified that Toxoplasma-injected neurons (TINs) are heterogeneously distributed throughout the brain. Unfortunately, standard methods to quantify and map heterogeneous cell populations onto a reference brain atlas are time consuming and prone to user bias. We developed a novel MATLAB-based semi-automated quantification and mapping program to allow the rapid and consistent mapping of heterogeneously distributed cells on to the Allen Institute Mouse Brain Atlas. The system uses two-threshold background subtraction to identify and quantify cells of interest. We demonstrate that we reliably quantify and neuroanatomically localize TINs with low intra- or inter-observer variability. In a follow up experiment, we show that specific regions of the mouse brain are enriched with TINs. The procedure we use takes advantage of simple immunohistochemistry labeling techniques, use of a standard microscope with a motorized stage, and low cost computing that can be readily obtained at a research institute. To our knowledge there is no other program that uses such readily available techniques and equipment for mapping heterogeneous populations of cells across the whole mouse brain. The quantification method described here allows reliable visualization, quantification, and mapping of heterogeneous cell populations in immunolabeled sections across whole mouse brains. Copyright © 2018 Elsevier B.V. All rights reserved.

  5. Functional MRI mapping of visual function and selective attention for performance assessment and presurgical planning using conjunctive visual search.

    PubMed

    Parker, Jason G; Zalusky, Eric J; Kirbas, Cemil

    2014-03-01

    Accurate mapping of visual function and selective attention using fMRI is important in the study of human performance as well as in presurgical treatment planning of lesions in or near visual centers of the brain. Conjunctive visual search (CVS) is a useful tool for mapping visual function during fMRI because of its greater activation extent compared with high-capacity parallel search processes. The purpose of this work was to develop and evaluate a CVS that was capable of generating consistent activation in the basic and higher level visual areas of the brain by using a high number of distractors as well as an optimized contrast condition. Images from 10 healthy volunteers were analyzed and brain regions of greatest activation and deactivation were determined using a nonbiased decomposition of the results at the hemisphere, lobe, and gyrus levels. The results were quantified in terms of activation and deactivation extent and mean z-statistic. The proposed CVS was found to generate robust activation of the occipital lobe, as well as regions in the middle frontal gyrus associated with coordinating eye movements and in regions of the insula associated with task-level control and focal attention. As expected, the task demonstrated deactivation patterns commonly implicated in the default-mode network. Further deactivation was noted in the posterior region of the cerebellum, most likely associated with the formation of optimal search strategy. We believe the task will be useful in studies of visual and selective attention in the neuroscience community as well as in mapping visual function in clinical fMRI.

  6. Direct evidence from intraoperative electrocortical stimulation indicates shared and distinct speech production center between Chinese and English languages.

    PubMed

    Wu, Jinsong; Lu, Junfeng; Zhang, Han; Zhang, Jie; Yao, Chengjun; Zhuang, Dongxiao; Qiu, Tianming; Guo, Qihao; Hu, Xiaobing; Mao, Ying; Zhou, Liangfu

    2015-12-01

    Chinese processing has been suggested involving distinct brain areas from English. However, current functional localization studies on Chinese speech processing use mostly "indirect" techniques such as functional magnetic resonance imaging and electroencephalography, lacking direct evidence by means of electrocortical recording. In this study, awake craniotomies in 66 Chinese-speaking glioma patients provide a unique opportunity to directly map eloquent language areas. Intraoperative electrocortical stimulation was conducted and the positive sites for speech arrest, anomia, and alexia were identified separately. With help of stereotaxic neuronavigation system and computational modeling, all positive sites elicited by stimulation were integrated and a series of two- and three-dimension Chinese language probability maps were built. We performed statistical comparisons between the Chinese maps and previously derived English maps. While most Chinese speech arrest areas located at typical language production sites (i.e., 50% positive sites in ventral precentral gyrus, 28% in pars opercularis and pars triangularis), which also serve English production, an additional brain area, the left middle frontal gyrus (Brodmann's areas 6/9), was found to be unique in Chinese production (P < 0.05). Moreover, Chinese speakers' inferior ventral precentral gyrus (Brodmann's area 6) was used more than that in English speakers. Our finding suggests that Chinese involves more perisylvian region (extending to left middle frontal gyrus) than English. This is the first time that direct evidence supports cross-cultural neurolinguistics differences in human beings. The Chinese language atlas will also helpful in brain surgery planning for Chinese-speakers. Copyright © 2015 Wiley Periodicals, Inc.

  7. 3D resolved mapping of optical aberrations in thick tissues

    PubMed Central

    Zeng, Jun; Mahou, Pierre; Schanne-Klein, Marie-Claire; Beaurepaire, Emmanuel; Débarre, Delphine

    2012-01-01

    We demonstrate a simple method for mapping optical aberrations with 3D resolution within thick samples. The method relies on the local measurement of the variation in image quality with externally applied aberrations. We discuss the accuracy of the method as a function of the signal strength and of the aberration amplitude and we derive the achievable resolution for the resulting measurements. We then report on measured 3D aberration maps in human skin biopsies and mouse brain slices. From these data, we analyse the consequences of tissue structure and refractive index distribution on aberrations and imaging depth in normal and cleared tissue samples. The aberration maps allow the estimation of the typical aplanetism region size over which aberrations can be uniformly corrected. This method and data pave the way towards efficient correction strategies for tissue imaging applications. PMID:22876353

  8. Cortical Cartography and Caret Software

    PubMed Central

    Van Essen, David C.

    2011-01-01

    Caret software is widely used for analyzing and visualizing many types of fMRI data, often in conjunction with experimental data from other modalities. This article places Caret’s development in a historical context that spans three decades of brain mapping – from the early days of manually generated flat maps to the nascent field of human connectomics. It also highlights some of Caret’s distinctive capabilities. This includes the ease of visualizing data on surfaces and/or volumes and on atlases as well as individual subjects. Caret can display many types of experimental data using various combinations of overlays (e.g., fMRI activation maps, cortical parcellations, areal boundaries), and it has other features that facilitate the analysis and visualization of complex neuroimaging datasets. PMID:22062192

  9. Mapping the stability of human brain asymmetry across five sex-chromosome aneuploidies.

    PubMed

    Lin, Amy; Clasen, Liv; Lee, Nancy Raitano; Wallace, Gregory L; Lalonde, Francois; Blumenthal, Jonathan; Giedd, Jay N; Raznahan, Armin

    2015-01-07

    The human brain displays stereotyped and early emerging patterns of cortical asymmetry in health. It is unclear if these asymmetries are highly sensitive to genetic and environmental variation or fundamental features of the brain that can survive severe developmental perturbations. To address this question, we mapped cortical thickness (CT) asymmetry in a group of genetically defined disorders known to impact CT development. Participants included 137 youth with one of five sex-chromosome aneuploidies [SCAs; XXX (n = 28), XXY (n = 58), XYY (n = 26), XXYY (n = 20), and XXXXY (n = 5)], and 169 age-matched typically developing controls (80 female). In controls, we replicated previously reported rightward inferior frontal and leftward lateral parietal CT asymmetry. These opposing frontoparietal CT asymmetries were broadly preserved in all five SCA groups. However, we also detected foci of shifting CT asymmetry with aneuploidy, which fell almost exclusively within regions of significant CT asymmetry in controls. Specifically, X-chromosome aneuploidy accentuated normative rightward inferior frontal asymmetries, while Y-chromosome aneuploidy reversed normative rightward medial prefrontal and lateral temporal asymmetries. These findings indicate that (1) the stereotyped normative pattern of opposing frontoparietal CT asymmetry arises from developmental mechanisms that can withstand gross chromosomal aneuploidy and (2) X and Y chromosomes can exert focal, nonoverlapping and directionally opposed influences on CT asymmetry within cortical regions of significant asymmetry in health. Our study attests to the resilience of developmental mechanisms that support the global patterning of CT asymmetry in humans, and motivates future research into the molecular bases and functional consequences of sex chromosome dosage effects on CT asymmetry. Copyright © 2015 the authors 0270-6474/15/350140-06$15.00/0.

  10. Naturalistic FMRI mapping reveals superior temporal sulcus as the hub for the distributed brain network for social perception.

    PubMed

    Lahnakoski, Juha M; Glerean, Enrico; Salmi, Juha; Jääskeläinen, Iiro P; Sams, Mikko; Hari, Riitta; Nummenmaa, Lauri

    2012-01-01

    Despite the abundant data on brain networks processing static social signals, such as pictures of faces, the neural systems supporting social perception in naturalistic conditions are still poorly understood. Here we delineated brain networks subserving social perception under naturalistic conditions in 19 healthy humans who watched, during 3-T functional magnetic resonance imaging (fMRI), a set of 137 short (approximately 16 s each, total 27 min) audiovisual movie clips depicting pre-selected social signals. Two independent raters estimated how well each clip represented eight social features (faces, human bodies, biological motion, goal-oriented actions, emotion, social interaction, pain, and speech) and six filler features (places, objects, rigid motion, people not in social interaction, non-goal-oriented action, and non-human sounds) lacking social content. These ratings were used as predictors in the fMRI analysis. The posterior superior temporal sulcus (STS) responded to all social features but not to any non-social features, and the anterior STS responded to all social features except bodies and biological motion. We also found four partially segregated, extended networks for processing of specific social signals: (1) a fronto-temporal network responding to multiple social categories, (2) a fronto-parietal network preferentially activated to bodies, motion, and pain, (3) a temporo-amygdalar network responding to faces, social interaction, and speech, and (4) a fronto-insular network responding to pain, emotions, social interactions, and speech. Our results highlight the role of the pSTS in processing multiple aspects of social information, as well as the feasibility and efficiency of fMRI mapping under conditions that resemble the complexity of real life.

  11. Frontal eye field, where art thou? Anatomy, function, and non-invasive manipulation of frontal regions involved in eye movements and associated cognitive operations

    PubMed Central

    Vernet, Marine; Quentin, Romain; Chanes, Lorena; Mitsumasu, Andres; Valero-Cabré, Antoni

    2014-01-01

    The planning, control and execution of eye movements in 3D space relies on a distributed system of cortical and subcortical brain regions. Within this network, the Eye Fields have been described in animals as cortical regions in which electrical stimulation is able to trigger eye movements and influence their latency or accuracy. This review focuses on the Frontal Eye Field (FEF) a “hub” region located in Humans in the vicinity of the pre-central sulcus and the dorsal-most portion of the superior frontal sulcus. The straightforward localization of the FEF through electrical stimulation in animals is difficult to translate to the healthy human brain, particularly with non-invasive neuroimaging techniques. Hence, in the first part of this review, we describe attempts made to characterize the anatomical localization of this area in the human brain. The outcome of functional Magnetic Resonance Imaging (fMRI), Magneto-encephalography (MEG) and particularly, non-invasive mapping methods such a Transcranial Magnetic Stimulation (TMS) are described and the variability of FEF localization across individuals and mapping techniques are discussed. In the second part of this review, we will address the role of the FEF. We explore its involvement both in the physiology of fixation, saccade, pursuit, and vergence movements and in associated cognitive processes such as attentional orienting, visual awareness and perceptual modulation. Finally in the third part, we review recent evidence suggesting the high level of malleability and plasticity of these regions and associated networks to non-invasive stimulation. The exploratory, diagnostic, and therapeutic interest of such interventions for the modulation and improvement of perception in 3D space are discussed. PMID:25202241

  12. From blood oxygenation level dependent (BOLD) signals to brain temperature maps.

    PubMed

    Sotero, Roberto C; Iturria-Medina, Yasser

    2011-11-01

    A theoretical framework is presented for converting Blood Oxygenation Level Dependent (BOLD) images to brain temperature maps, based on the idea that disproportional local changes in cerebral blood flow (CBF) as compared with cerebral metabolic rate of oxygen consumption (CMRO₂) during functional brain activity, lead to both brain temperature changes and the BOLD effect. Using an oxygen limitation model and a BOLD signal model, we obtain a transcendental equation relating CBF and CMRO₂ changes with the corresponding BOLD signal, which is solved in terms of the Lambert W function. Inserting this result in the dynamic bioheat equation describing the rate of temperature changes in the brain, we obtain a nonautonomous ordinary differential equation that depends on the BOLD response, which is solved numerically for each brain voxel. Temperature maps obtained from a real BOLD dataset registered in an attention to visual motion experiment were calculated, obtaining temperature variations in the range: (-0.15, 0.1) which is consistent with experimental results. The statistical analysis revealed that significant temperature activations have a similar distribution pattern than BOLD activations. An interesting difference was the activation of the precuneus in temperature maps, a region involved in visuospatial processing, an effect that was not observed on BOLD maps. Furthermore, temperature maps were more localized to gray matter regions than the original BOLD maps, showing less activated voxels in white matter and cerebrospinal fluid.

  13. Proton magnetic resonance spectroscopy imaging in the study of human brain cancer.

    PubMed

    Martínez-Bisbal, M C; Celda, B

    2009-12-01

    Magnetic resonance spectroscopic imaging (MRSI) is a non-invasive imaging technique that provides metabolic information on brain tumor. This biochemical information can be processed and presented as density maps of several metabolites, among them N-acetylaspartate (marker of neuronal viability), choline (marker of membrane turnover), creatine (related to the energy state of the cells), myo-Inositol (exclusively found in astrocytes), lipids and lactate (observed in necrosis and other pathological processes) which mean relevant information in the context of brain tumors. Thus, this technique is a multiparametrical molecular imaging method that can complete the magnetic resonance imaging (MRI) study enabling the detection of biochemical patterns of different features and aspects of brain tumors. In this article, the role of MRSI as a molecular imaging technique to provide biochemical information on human brain tumors is reviewed. The most frequent questions and situations in the study of human brain tumors in clinical settings will be considered, as well as the distinction of neoplastic lesions from non neoplastic, the tumor type identification, the study of heterogeneity and infiltration of normal appearing white matter and the therapy following with detection of side effects. The great amount of data in MRSI acquisition compared to the single voxel techniques requires the use of automated methods of quantification, but the possibility to obtain self-reference in the non-affected areas allows different strategies for data handling and interpretation, as presented in the literature. The combination of MRSI with other physiological MRI techniques and positron emission tomography is also included in this review.

  14. Resonance Raman imaging for detecting and monitoring molecular pathological changes in human brain tumors related to Warburg effect

    NASA Astrophysics Data System (ADS)

    Zhou, Yan; Liu, Cheng-hui; Zhu, Ke; Zhang, Chunyuan; Yang, Yang; Yu, Xinguang; Hu, Hailong; Cheng, Gangge; Wu, Binlin; Shi, Lingyan; Alfano, Robert R.

    2018-02-01

    The goal of the research is to determine the prognostic molecular pathological changes in components and composition, for human brain glioma gradings in comparison with normal tissues in three-dimensional Raman imaging profiles by visible Resonance Raman (VRR) imaging. VRR images from twenty-five specimens including three healthy tissues, one normal control, and twenty-one glioma tissues of grades II, II-III and III-IV with histology examination were measured and investigated using WITec300R confocal micro Raman imaging system with laser excitation of 532nm. Two-dimensional RR spectral mappings performed in 20μm x 20μm generated 400 images which integrated the intensity of the specific biochemical bonds as the third dimension. The three-dimension (3D) map demonstrated the spatial distributions of three selected sets of RR spectra of molecular biomarkers, and revealed significant differences in the spectra between normal and glioma tissues of different grades due to the composition changes in key molimageecules. These RR molecular spectral fingerprints have displayed: a clear enhancement of RR vibrational modes at 1129-1131cm-1 and 2934cm-1 which are supposed to be arising from lipoproteins; evident decreased RR vibrational modes at 1442cm-1 and 2854cm-1 which are from saturated fatty acids bonds in all-grades of glioma brain tissues compared with normal tissues; and the enhanced RR spectral modes of 1129 cm-1 and 2938cm-1 which suggest contribution from lactate. These findings may provide a novel proof for anaerobic glycolysis metabolic process in brain glioma cancer tissues that has been explained by Warburg effects.

  15. ["Dieu et cerveau, rien que Dieu et cerveau!" Johann Gottfried von Herder (1744-1803) and the neurosciences of this time].

    PubMed

    Stahnisch, Frank

    2007-01-01

    The impact of Johann Gottfried von Herder on the broad spectrum of the history of ideas can hardly be estimated by separate categories derived from individual disciplines. It transcends the spheres of philosophy, theology, historiography and even medical anthropology--also because Herder, unlike many of his contemporary philosophers and hommes de lettres, was particularly interested in the neurophysiological and -anatomical investigations of his time. Herder's universal interest in human learning is reflected in numerous personal contacts to contemporary academic scholars and natural scientists, such as the Swiss theologian Johann Caspar Lavater, whose physiognomic doctrine mapped out a comprehensive research programme on character analysis, or the Mainz anatomist Samuel Thomas von Soemmering. Herder tightly received the latter's assumption about the interplay between the human soul and the anatomy of the brain. In this article, it shall be demonstrated that Herder's neurophilosophy was primarily influenced by a "pandynamic assumption of nature" and that it designated the brain centrally as a "working tool of God"--right between the human faculties of rationality, feeling and bodily development. The attractiveness of this concept to both basic brain research and clinical neurology was a result of his anthropological approach which combined latest developments in the natural sciences with a central perspective on the human sciences.

  16. Mapping cell-specific functional connections in the mouse brain using ChR2-evoked hemodynamics (Conference Presentation)

    NASA Astrophysics Data System (ADS)

    Bauer, Adam Q.; Kraft, Andrew; Baxter, Grant A.; Bruchas, Michael; Lee, Jin-Moo; Culver, Joseph P.

    2017-02-01

    Functional magnetic resonance imaging (fMRI) has transformed our understanding of the brain's functional organization. However, mapping subunits of a functional network using hemoglobin alone presents several disadvantages. Evoked and spontaneous hemodynamic fluctuations reflect ensemble activity from several populations of neurons making it difficult to discern excitatory vs inhibitory network activity. Still, blood-based methods of brain mapping remain powerful because hemoglobin provides endogenous contrast in all mammalian brains. To add greater specificity to hemoglobin assays, we integrated optical intrinsic signal(OIS) imaging with optogenetic stimulation to create an Opto-OIS mapping tool that combines the cell-specificity of optogenetics with label-free, hemoglobin imaging. Before mapping, titrated photostimuli determined which stimulus parameters elicited linear hemodynamic responses in the cortex. Optimized stimuli were then scanned over the left hemisphere to create a set of optogenetically-defined effective connectivity (Opto-EC) maps. For many sites investigated, Opto-EC maps exhibited higher spatial specificity than those determined using spontaneous hemodynamic fluctuations. For example, resting-state functional connectivity (RS-FC) patterns exhibited widespread ipsilateral connectivity while Opto-EC maps contained distinct short- and long-range constellations of ipsilateral connectivity. Further, RS-FC maps were usually symmetric about midline while Opto-EC maps displayed more heterogeneous contralateral homotopic connectivity. Both Opto-EC and RS-FC patterns were compared to mouse connectivity data from the Allen Institute. Unlike RS-FC maps, Thy1-based maps collected in awake, behaving mice closely recapitulated the connectivity structure derived using ex vivo anatomical tracer methods. Opto-OIS mapping could be a powerful tool for understanding cellular and molecular contributions to network dynamics and processing in the mouse brain.

  17. A brief review on the history of human functional near-infrared spectroscopy (fNIRS) development and fields of application.

    PubMed

    Ferrari, Marco; Quaresima, Valentina

    2012-11-01

    This review is aimed at celebrating the upcoming 20th anniversary of the birth of human functional near-infrared spectroscopy (fNIRS). After the discovery in 1992 that the functional activation of the human cerebral cortex (due to oxygenation and hemodynamic changes) can be explored by NIRS, human functional brain mapping research has gained a new dimension. fNIRS or optical topography, or near-infrared imaging or diffuse optical imaging is used mainly to detect simultaneous changes in optical properties of the human cortex from multiple measurement sites and displays the results in the form of a map or image over a specific area. In order to place current fNIRS research in its proper context, this paper presents a brief historical overview of the events that have shaped the present status of fNIRS. In particular, technological progresses of fNIRS are highlighted (i.e., from single-site to multi-site functional cortical measurements (images)), introduction of the commercial multi-channel systems, recent commercial wireless instrumentation and more advanced prototypes. Copyright © 2012 Elsevier Inc. All rights reserved.

  18. Connectivity-based parcellation of human cingulate cortex and its relation to functional specialization.

    PubMed

    Beckmann, Matthias; Johansen-Berg, Heidi; Rushworth, Matthew F S

    2009-01-28

    Whole-brain neuroimaging studies have demonstrated regional variations in function within human cingulate cortex. At the same time, regional variations in cingulate anatomical connections have been found in animal models. It has, however, been difficult to estimate the relationship between connectivity and function throughout the whole cingulate cortex within the human brain. In this study, magnetic resonance diffusion tractography was used to investigate cingulate probabilistic connectivity in the human brain with two approaches. First, an algorithm was used to search for regional variations in the probabilistic connectivity profiles of all cingulate cortex voxels with the whole of the rest of the brain. Nine subregions with distinctive connectivity profiles were identified. It was possible to characterize several distinct areas in the dorsal cingulate sulcal region. Several distinct regions were also found in subgenual and perigenual cortex. Second, the probabilities of connection between cingulate cortex and 11 predefined target regions of interest were calculated. Cingulate voxels with a high probability of connection with the different targets formed separate clusters within cingulate cortex. Distinct connectivity fingerprints characterized the likelihood of connections between the extracingulate target regions and the nine cingulate subregions. Last, a meta-analysis of 171 functional studies reporting cingulate activation was performed. Seven different cognitive conditions were selected and peak activation coordinates were plotted to create maps of functional localization within the cingulate cortex. Regional functional specialization was found to be related to regional differences in probabilistic anatomical connectivity.

  19. Investigating common coding of observed and executed actions in the monkey brain using cross-modal multi-variate fMRI classification.

    PubMed

    Fiave, Prosper Agbesi; Sharma, Saloni; Jastorff, Jan; Nelissen, Koen

    2018-05-19

    Mirror neurons are generally described as a neural substrate hosting shared representations of actions, by simulating or 'mirroring' the actions of others onto the observer's own motor system. Since single neuron recordings are rarely feasible in humans, it has been argued that cross-modal multi-variate pattern analysis (MVPA) of non-invasive fMRI data is a suitable technique to investigate common coding of observed and executed actions, allowing researchers to infer the presence of mirror neurons in the human brain. In an effort to close the gap between monkey electrophysiology and human fMRI data with respect to the mirror neuron system, here we tested this proposal for the first time in the monkey. Rhesus monkeys either performed reach-and-grasp or reach-and-touch motor acts with their right hand in the dark or observed videos of human actors performing similar motor acts. Unimodal decoding showed that both executed or observed motor acts could be decoded from numerous brain regions. Specific portions of rostral parietal, premotor and motor cortices, previously shown to house mirror neurons, in addition to somatosensory regions, yielded significant asymmetric action-specific cross-modal decoding. These results validate the use of cross-modal multi-variate fMRI analyses to probe the representations of own and others' actions in the primate brain and support the proposed mapping of others' actions onto the observer's own motor cortices. Copyright © 2018 Elsevier Inc. All rights reserved.

  20. Rich club network analysis shows distinct patterns of disruption in frontotemporal dementia and Alzheimer’s disease

    PubMed Central

    Daianu, Madelaine; Jahanshad, Neda; Villalon-Reina, Julio E.; Mendez, Mario F.; Bartzokis, George; Jimenez, Elvira E.; Joshi, Aditi; Barsuglia, Joseph; Thompson, Paul M.

    2015-01-01

    Diffusion imaging and brain connectivity analyses can reveal the underlying organizational patterns of the human brain, described as complex networks of densely interlinked regions. Here, we analyzed 1.5-Tesla whole-brain diffusion-weighted images from 64 participants – 15 patients with behavioral variant frontotemporal (bvFTD) dementia, 19 with early-onset Alzheimer’s disease (EOAD), and 30 healthy elderly controls. Based on whole-brain tractography, we reconstructed structural brain connectivity networks to map connections between cortical regions. We examined how bvFTD and EOAD disrupt the weighted ‘rich club’ – a network property where high-degree network nodes are more interconnected than expected by chance. bvFTD disrupts both the nodal and global organization of the network in both low- and high-degree regions of the brain. EOAD targets the global connectivity of the brain, mainly affecting the fiber density of high-degree (highly connected) regions that form the rich club network. These rich club analyses suggest distinct patterns of disruptions among different forms of dementia. PMID:26161050

  1. Neuroplasticity in post-stroke gait recovery and noninvasive brain stimulation

    PubMed Central

    Xu, Yi; Hou, Qing-hua; Russell, Shawn D.; Bennett, Bradford C.; Sellers, Andrew J.; Lin, Qiang; Huang, Dong-feng

    2015-01-01

    Gait disorders drastically affect the quality of life of stroke survivors, making post-stroke rehabilitation an important research focus. Noninvasive brain stimulation has potential in facilitating neuroplasticity and improving post-stroke gait impairment. However, a large inter-individual variability in the response to noninvasive brain stimulation interventions has been increasingly recognized. We first review the neurophysiology of human gait and post-stroke neuroplasticity for gait recovery, and then discuss how noninvasive brain stimulation techniques could be utilized to enhance gait recovery. While post-stroke neuroplasticity for gait recovery is characterized by use-dependent plasticity, it evolves over time, is idiosyncratic, and may develop maladaptive elements. Furthermore, noninvasive brain stimulation has limited reach capability and is facilitative-only in nature. Therefore, we recommend that noninvasive brain stimulation be used adjunctively with rehabilitation training and other concurrent neuroplasticity facilitation techniques. Additionally, when noninvasive brain stimulation is applied for the rehabilitation of gait impairment in stroke survivors, stimulation montages should be customized according to the specific types of neuroplasticity found in each individual. This could be done using multiple mapping techniques. PMID:26889202

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

    PubMed

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

    2015-08-01

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

  3. Biomechanical Analysis of Normal Brain Development during the First Year of Life Using Finite Strain Theory.

    PubMed

    Kim, Jeong Chul; Wang, Li; Shen, Dinggang; Lin, Weili

    2016-12-02

    The first year of life is the most critical time period for structural and functional development of the human brain. Combining longitudinal MR imaging and finite strain theory, this study aimed to provide new insights into normal brain development through a biomechanical framework. Thirty-three normal infants were longitudinally imaged using MRI from 2 weeks to 1 year of age. Voxel-wise Jacobian determinant was estimated to elucidate volumetric changes while Lagrange strains (both normal and shear strains) were measured to reveal directional growth information every 3 months during the first year of life. Directional normal strain maps revealed that, during the first 6 months, the growth pattern of gray matter is anisotropic and spatially inhomogeneous with higher left-right stretch around the temporal lobe and interhemispheric fissure, anterior-posterior stretch in the frontal and occipital lobes, and superior-inferior stretch in right inferior occipital and right inferior temporal gyri. In contrast, anterior lateral ventricles and insula showed an isotropic stretch pattern. Volumetric and directional growth rates were linearly decreased with age for most of the cortical regions. Our results revealed anisotropic and inhomogeneous brain growth patterns of the human brain during the first year of life using longitudinal MRI and a biomechanical framework.

  4. Understanding human visual systems and its impact on our intelligent instruments

    NASA Astrophysics Data System (ADS)

    Strojnik Scholl, Marija; Páez, Gonzalo; Scholl, Michelle K.

    2013-09-01

    We review the evolution of machine vision and comment on the cross-fertilization from the neural sciences onto flourishing fields of neural processing, parallel processing, and associative memory in optical sciences and computing. Then we examine how the intensive efforts in mapping the human brain have been influenced by concepts in computer sciences, control theory, and electronic circuits. We discuss two neural paths that employ the input from the vision sense to determine the navigational options and object recognition. They are ventral temporal pathway for object recognition (what?) and dorsal parietal pathway for navigation (where?), respectively. We describe the reflexive and conscious decision centers in cerebral cortex involved with visual attention and gaze control. Interestingly, these require return path though the midbrain for ocular muscle control. We find that the cognitive psychologists currently study human brain employing low-spatial-resolution fMRI with temporal response on the order of a second. In recent years, the life scientists have concentrated on insect brains to study neural processes. We discuss how reflexive and conscious gaze-control decisions are made in the frontal eye field and inferior parietal lobe, constituting the fronto-parietal attention network. We note that ethical and experiential learnings impact our conscious decisions.

  5. A Scalable Framework For Segmenting Magnetic Resonance Images

    PubMed Central

    Hore, Prodip; Goldgof, Dmitry B.; Gu, Yuhua; Maudsley, Andrew A.; Darkazanli, Ammar

    2009-01-01

    A fast, accurate and fully automatic method of segmenting magnetic resonance images of the human brain is introduced. The approach scales well allowing fast segmentations of fine resolution images. The approach is based on modifications of the soft clustering algorithm, fuzzy c-means, that enable it to scale to large data sets. Two types of modifications to create incremental versions of fuzzy c-means are discussed. They are much faster when compared to fuzzy c-means for medium to extremely large data sets because they work on successive subsets of the data. They are comparable in quality to application of fuzzy c-means to all of the data. The clustering algorithms coupled with inhomogeneity correction and smoothing are used to create a framework for automatically segmenting magnetic resonance images of the human brain. The framework is applied to a set of normal human brain volumes acquired from different magnetic resonance scanners using different head coils, acquisition parameters and field strengths. Results are compared to those from two widely used magnetic resonance image segmentation programs, Statistical Parametric Mapping and the FMRIB Software Library (FSL). The results are comparable to FSL while providing significant speed-up and better scalability to larger volumes of data. PMID:20046893

  6. Twenty-first century brain banking. Processing brains for research: the Columbia University methods

    PubMed Central

    del Amaya, Maria Pilar; Keller, Christian E.

    2007-01-01

    Carefully categorized postmortem human brains are crucial for research. The lack of generally accepted methods for processing human postmortem brains for research persists. Thus, brain banking is essential; however, it cannot be achieved at the cost of the teaching mission of the academic institution by routing brains away from residency programs, particularly when the autopsy rate is steadily decreasing. A consensus must be reached whereby a brain can be utilizable for diagnosis, research, and teaching. The best diagnostic categorization possible must be secured and the yield of samples for basic investigation maximized. This report focuses on integrated, novel methods currently applied at the New York Brain Bank, Columbia University, New York, which are designed to reach accurate neuropathological diagnosis, optimize the yield of samples, and process fresh-frozen samples suitable for a wide range of modern investigations. The brains donated for research are processed as soon as possible after death. The prosector must have a good command of the neuroanatomy, neuropathology, and the protocol. One half of each brain is immersed in formalin for performing the thorough neuropathologic evaluation, which is combined with the teaching task. The contralateral half is extensively dissected at the fresh state. The anatomical origin of each sample is recorded using the map of Brodmann for the cortical samples. The samples are frozen at −160°C, barcode labeled, and ready for immediate disbursement once categorized diagnostically. A rigorous organization of freezer space, coupled to an electronic tracking system with its attached software, fosters efficient access for retrieval within minutes of any specific frozen samples in storage. This report describes how this achievement is feasible with emphasis on the actual processing of brains donated for research. PMID:17985145

  7. Neuroprotection by selective neuronal deletion of Atg7 in neonatal brain injury

    PubMed Central

    Xie, Cuicui; Ginet, Vanessa; Sun, Yanyan; Koike, Masato; Zhou, Kai; Li, Tao; Li, Hongfu; Li, Qian; Wang, Xiaoyang; Uchiyama, Yasuo; Truttmann, Anita C.; Kroemer, Guido; Puyal, Julien; Blomgren, Klas; Zhu, Changlian

    2016-01-01

    ABSTRACT Perinatal asphyxia induces neuronal cell death and brain injury, and is often associated with irreversible neurological deficits in children. There is an urgent need to elucidate the neuronal death mechanisms occurring after neonatal hypoxia-ischemia (HI). We here investigated the selective neuronal deletion of the Atg7 (autophagy related 7) gene on neuronal cell death and brain injury in a mouse model of severe neonatal hypoxia-ischemia. Neuronal deletion of Atg7 prevented HI-induced autophagy, resulted in 42% decrease of tissue loss compared to wild-type mice after the insult, and reduced cell death in multiple brain regions, including apoptosis, as shown by decreased caspase-dependent and -independent cell death. Moreover, we investigated the lentiform nucleus of human newborns who died after severe perinatal asphyxia and found increased neuronal autophagy after severe hypoxic-ischemic encephalopathy compared to control uninjured brains, as indicated by the numbers of MAP1LC3B/LC3B (microtubule-associated protein 1 light chain 3)-, LAMP1 (lysosomal-associated membrane protein 1)-, and CTSD (cathepsin D)-positive cells. These findings reveal that selective neuronal deletion of Atg7 is strongly protective against neuronal death and overall brain injury occurring after HI and suggest that inhibition of HI-enhanced autophagy should be considered as a potential therapeutic target for the treatment of human newborns developing severe hypoxic-ischemic encephalopathy. PMID:26727396

  8. Integration of transcriptomic and cytoarchitectonic data implicates a role for MAOA and TAC1 in the limbic-cortical network.

    PubMed

    Bludau, Sebastian; Mühleisen, Thomas W; Eickhoff, Simon B; Hawrylycz, Michael J; Cichon, Sven; Amunts, Katrin

    2018-06-01

    Decoding the chain from genes to cognition requires detailed insights how areas with specific gene activities and microanatomical architectures contribute to brain function and dysfunction. The Allen Human Brain Atlas contains regional gene expression data, while the JuBrain Atlas offers three-dimensional cytoarchitectonic maps reflecting interindividual variability. To date, an integrated framework that combines the analytical benefits of both scientific platforms towards a multi-level brain atlas of adult humans was not available. We have, therefore, developed JuGEx, a new method for integrating tissue transcriptome and cytoarchitectonic segregation. We investigated differential gene expression in two JuBrain areas of the frontal pole that we have structurally and functionally characterized in previous studies. Our results show a significant upregulation of MAOA and TAC1 in the medial area frontopolaris which is a node in the limbic-cortical network and known to be susceptible for gray matter loss and behavioral dysfunction in patients with depression. The MAOA gene encodes an enzyme which is involved in the catabolism of dopamine, norepinephrine, serotonin, and other monoaminergic neurotransmitters. The TAC1 locus generates hormones that play a role in neuron excitations and behavioral responses. Overall, JuGEx provides a new tool for the scientific community that empowers research from basic, cognitive and clinical neuroscience in brain regions and disease models with regard to gene expression.

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

    PubMed

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

    2016-05-01

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

  10. Phase-difference and spectroscopic imaging for monitoring of human brain temperature during cooling.

    PubMed

    Weis, Jan; Covaciu, Lucian; Rubertsson, Sten; Allers, Mats; Lunderquist, Anders; Ortiz-Nieto, Francisco; Ahlström, Håkan

    2012-12-01

    Decrease of the human brain temperature was induced by intranasal cooling. The main purpose of this study was to compare the two magnetic resonance methods for monitoring brain temperature changes during cooling: phase-difference and magnetic resonance spectroscopic imaging (MRSI) with high spatial resolution. Ten healthy volunteers were measured. Selective brain cooling was performed through nasal cavities using saline-cooled balloon catheters. MRSI was based on a radiofrequency spoiled gradient echo sequence. The spectral information was encoded by incrementing the echo time of the subsequent eight image records. Reconstructed voxel size was 1×1×5 mm(3). Relative brain temperature was computed from the positions of water spectral lines. Phase maps were obtained from the first image record of the MRSI sequence. Mild hypothermia was achieved in 15-20 min. Mean brain temperature reduction varied in the interval <-3.0; -0.6>°C and <-2.7; -0.7>°C as measured by the MRSI and phase-difference methods, respectively. Very good correlation was found in all locations between the temperatures measured by both techniques except in the frontal lobe. Measurements in the transversal slices were more robust to the movement artifacts than those in the sagittal planes. Good agreement was found between the MRSI and phase-difference techniques. Copyright © 2012 Elsevier Inc. All rights reserved.

  11. Cerebral cortex three-dimensional profiling in human fetuses by magnetic resonance imaging

    PubMed Central

    Sbarbati, Andrea; Pizzini, Francesca; Fabene, Paolo F; Nicolato, Elena; Marzola, Pasquina; Calderan, Laura; Simonati, Alessandro; Longo, Laura; Osculati, Antonio; Beltramello, Alberto

    2004-01-01

    Seven human fetuses of crown/rump length corresponding to gestational ages ranging from the 12th to the 16th week were studied using a paradigm based on three-dimensional reconstruction of the brain obtained by magnetic resonance imaging (MRI). The aim of the study was to evaluate brain morphology in situ and to describe developmental dynamics during an important period of fetal morphogenesis. Three-dimensional MRI showed the increasing degree of maturation of the brains; fronto-occipital distance, bitemporal distance and occipital angle were examined in all the fetuses. The data were interpreted by correlation with the internal structure as visualized using high-spatial-resolution MRI, acquired using a 4.7-T field intensity magnet with a gradient power of 20 G cm−1. The spatial resolution was sufficient for a detailed detection of five layers, and the contrast was optimized using sequences with different degrees of T1 and T2 weighting. Using the latter, it was possible to visualize the subplate and marginal zones. The cortical thickness was mapped on to the hemispheric surface, describing the thickness gradient from the insular cortex to the periphery of the hemispheres. The study demonstrates the utility of MRI for studying brain development. The method provides a quantitative profiling of the brain, which allows the calculation of important morphological parameters, and it provides informative regarding transient features of the developing brain. PMID:15198688

  12. Corticostriatal connectivity fingerprints: Probability maps based on resting-state functional connectivity.

    PubMed

    Jaspers, Ellen; Balsters, Joshua H; Kassraian Fard, Pegah; Mantini, Dante; Wenderoth, Nicole

    2017-03-01

    Over the last decade, structure-function relationships have begun to encompass networks of brain areas rather than individual structures. For example, corticostriatal circuits have been associated with sensorimotor, limbic, and cognitive information processing, and damage to these circuits has been shown to produce unique behavioral outcomes in Autism, Parkinson's Disease, Schizophrenia and healthy ageing. However, it remains an open question how abnormal or absent connectivity can be detected at the individual level. Here, we provide a method for clustering gross morphological structures into subregions with unique functional connectivity fingerprints, and generate network probability maps usable as a baseline to compare individual cases against. We used connectivity metrics derived from resting-state fMRI (N = 100), in conjunction with hierarchical clustering methods, to parcellate the striatum into functionally distinct clusters. We identified three highly reproducible striatal subregions, across both hemispheres and in an independent replication dataset (N = 100) (dice-similarity values 0.40-1.00). Each striatal seed region resulted in a highly reproducible distinct connectivity fingerprint: the putamen showed predominant connectivity with cortical and cerebellar sensorimotor and language processing areas; the ventromedial striatum cluster had a distinct limbic connectivity pattern; the caudate showed predominant connectivity with the thalamus, frontal and occipital areas, and the cerebellum. Our corticostriatal probability maps agree with existing connectivity data in humans and non-human primates, and showed a high degree of replication. We believe that these maps offer an efficient tool to further advance hypothesis driven research and provide important guidance when investigating deviant connectivity in neurological patient populations suffering from e.g., stroke or cerebral palsy. Hum Brain Mapp 38:1478-1491, 2017. © 2016 Wiley Periodicals, Inc. © 2016 Wiley Periodicals, Inc.

  13. Adaptation, perceptual learning, and plasticity of brain functions.

    PubMed

    Horton, Jonathan C; Fahle, Manfred; Mulder, Theo; Trauzettel-Klosinski, Susanne

    2017-03-01

    The capacity for functional restitution after brain damage is quite different in the sensory and motor systems. This series of presentations highlights the potential for adaptation, plasticity, and perceptual learning from an interdisciplinary perspective. The chances for restitution in the primary visual cortex are limited. Some patterns of visual field loss and recovery after stroke are common, whereas others are impossible, which can be explained by the arrangement and plasticity of the cortical map. On the other hand, compensatory mechanisms are effective, can occur spontaneously, and can be enhanced by training. In contrast to the human visual system, the motor system is highly flexible. This is based on special relationships between perception and action and between cognition and action. In addition, the healthy adult brain can learn new functions, e.g. increasing resolution above the retinal one. The significance of these studies for rehabilitation after brain damage will be discussed.

  14. Large-Scale Brain Simulation and Disorders of Consciousness. Mapping Technical and Conceptual Issues.

    PubMed

    Farisco, Michele; Kotaleski, Jeanette H; Evers, Kathinka

    2018-01-01

    Modeling and simulations have gained a leading position in contemporary attempts to describe, explain, and quantitatively predict the human brain's operations. Computer models are highly sophisticated tools developed to achieve an integrated knowledge of the brain with the aim of overcoming the actual fragmentation resulting from different neuroscientific approaches. In this paper we investigate the plausibility of simulation technologies for emulation of consciousness and the potential clinical impact of large-scale brain simulation on the assessment and care of disorders of consciousness (DOCs), e.g., Coma, Vegetative State/Unresponsive Wakefulness Syndrome, Minimally Conscious State. Notwithstanding their technical limitations, we suggest that simulation technologies may offer new solutions to old practical problems, particularly in clinical contexts. We take DOCs as an illustrative case, arguing that the simulation of neural correlates of consciousness is potentially useful for improving treatments of patients with DOCs.

  15. Brain systems underlying susceptibility to helplessness and depression.

    PubMed

    Shumake, J; Gonzalez-Lima, F

    2003-09-01

    There has been a relative lack of research into the neurobiological predispositions that confer vulnerability to depression. This article reviews functional brain mappings from a genetic animal model, the congenitally helpless rat, which is predisposed to develop learned helplessness. Neurometabolic findings from this model are integrated with the neuroscientific literature from other animal models of depression as well as depressed humans. Changes in four major brain systems are suggested to underlie susceptibility to helplessness and possibly depression: (a) an unbalanced prefrontal-cingulate cortical system, (b) a dissociated hypothalamic-pituitary-adrenal axis, (c) a dissociated septal-hippocampal system, and (d) a hypoactive brain reward system, as exemplified by a hypermetabolic habenula-interpeduncular nucleus pathway and a hypometabolic ventral tegmental area-striatum pathway. Functional interconnections and causal relationships among these systems are considered and further experiments are suggested, with theoretical attention to how an abnormality in any one system could affect the others.

  16. A dedicated network for social interaction processing in the primate brain.

    PubMed

    Sliwa, J; Freiwald, W A

    2017-05-19

    Primate cognition requires interaction processing. Interactions can reveal otherwise hidden properties of intentional agents, such as thoughts and feelings, and of inanimate objects, such as mass and material. Where and how interaction analyses are implemented in the brain is unknown. Using whole-brain functional magnetic resonance imaging in macaque monkeys, we discovered a network centered in the medial and ventrolateral prefrontal cortex that is exclusively engaged in social interaction analysis. Exclusivity of specialization was found for no other function anywhere in the brain. Two additional networks, a parieto-premotor and a temporal one, exhibited both social and physical interaction preference, which, in the temporal lobe, mapped onto a fine-grain pattern of object, body, and face selectivity. Extent and location of a dedicated system for social interaction analysis suggest that this function is an evolutionary forerunner of human mind-reading capabilities. Copyright © 2017, American Association for the Advancement of Science.

  17. Quantitative Assessment of Normal Fetal Brain Myelination Using Fast Macromolecular Proton Fraction Mapping.

    PubMed

    Yarnykh, V L; Prihod'ko, I Y; Savelov, A A; Korostyshevskaya, A M

    2018-05-10

    Fast macromolecular proton fraction mapping is a recently emerged MRI method for quantitative myelin imaging. Our aim was to develop a clinically targeted technique for macromolecular proton fraction mapping of the fetal brain and test its capability to characterize normal prenatal myelination. This prospective study included 41 pregnant women (gestational age range, 18-38 weeks) without abnormal findings on fetal brain MR imaging performed for clinical indications. A fast fetal brain macromolecular proton fraction mapping protocol was implemented on a clinical 1.5T MR imaging scanner without software modifications and was performed after a clinical examination with an additional scan time of <5 minutes. 3D macromolecular proton fraction maps were reconstructed from magnetization transfer-weighted, T1-weighted, and proton density-weighted images by the single-point method. Mean macromolecular proton fraction in the brain stem, cerebellum, and thalamus and frontal, temporal, and occipital WM was compared between structures and pregnancy trimesters using analysis of variance. Gestational age dependence of the macromolecular proton fraction was assessed using the Pearson correlation coefficient ( r ). The mean macromolecular proton fraction in the fetal brain structures varied between 2.3% and 4.3%, being 5-fold lower than macromolecular proton fraction in adult WM. The macromolecular proton fraction in the third trimester was higher compared with the second trimester in the brain stem, cerebellum, and thalamus. The highest macromolecular proton fraction was observed in the brain stem, followed by the thalamus, cerebellum, and cerebral WM. The macromolecular proton fraction in the brain stem, cerebellum, and thalamus strongly correlated with gestational age ( r = 0.88, 0.80, and 0.73; P < .001). No significant correlations were found for cerebral WM regions. Myelin is the main factor determining macromolecular proton fraction in brain tissues. Macromolecular proton fraction mapping is sensitive to the earliest stages of the fetal brain myelination and can be implemented in a clinical setting. © 2018 by American Journal of Neuroradiology.

  18. Brain functional BOLD perturbation modelling for forward fMRI and inverse mapping

    PubMed Central

    Robinson, Jennifer; Calhoun, Vince

    2018-01-01

    Purpose To computationally separate dynamic brain functional BOLD responses from static background in a brain functional activity for forward fMRI signal analysis and inverse mapping. Methods A brain functional activity is represented in terms of magnetic source by a perturbation model: χ = χ0 +δχ, with δχ for BOLD magnetic perturbations and χ0 for background. A brain fMRI experiment produces a timeseries of complex-valued images (T2* images), whereby we extract the BOLD phase signals (denoted by δP) by a complex division. By solving an inverse problem, we reconstruct the BOLD δχ dataset from the δP dataset, and the brain χ distribution from a (unwrapped) T2* phase image. Given a 4D dataset of task BOLD fMRI, we implement brain functional mapping by temporal correlation analysis. Results Through a high-field (7T) and high-resolution (0.5mm in plane) task fMRI experiment, we demonstrated in detail the BOLD perturbation model for fMRI phase signal separation (P + δP) and reconstructing intrinsic brain magnetic source (χ and δχ). We also provided to a low-field (3T) and low-resolution (2mm) task fMRI experiment in support of single-subject fMRI study. Our experiments show that the δχ-depicted functional map reveals bidirectional BOLD χ perturbations during the task performance. Conclusions The BOLD perturbation model allows us to separate fMRI phase signal (by complex division) and to perform inverse mapping for pure BOLD δχ reconstruction for intrinsic functional χ mapping. The full brain χ reconstruction (from unwrapped fMRI phase) provides a new brain tissue image that allows to scrutinize the brain tissue idiosyncrasy for the pure BOLD δχ response through an automatic function/structure co-localization. PMID:29351339

  19. Pharmacokinetic analysis and drug delivery efficiency of the focused ultrasound-induced blood-brain barrier opening in non-human primates

    PubMed Central

    Samiotaki, Gesthimani; Karakatsani, Maria Eleni; Buch, Amanda; Papadopoulos, Stephanos; Wu, Shih Ying; Jambawalikar, Sachin; Konofagou, Elisa E.

    2016-01-01

    Purpose Focused Ultrasound (FUS) in conjunction with systemically administered microbubbles has been shown to open the Blood-Brain Barrier (BBB) locally, non-invasively and reversibly in rodents and non-human primates (NHP), suggesting the immense potential of this technique. The objective of this study entailed the investigation of the physiologic changes in the brain following the FUS-induced BBB opening and their relationship with the underlying anatomy. Materials and Methods Pharmacokinetic analysis was implemented in NHP’s that received FUS at various acoustic pressures. Relaxivity mapping enabled the robust quantitative detection of the BBB opening as well as gray and white matter segmentation. Drug delivery efficiency was measured for pre-clinical validation of the technique. Results Based on our results, the opening volume and the amount of the gadolinium delivered were found mostly contained in the grey matter, while FUS-induced permeability and drug concentration varied depending upon the underlying brain inhomogeneity, and increased with the acoustic pressure. Conclusions Overall, apart from the in vivo protocols for BBB analysis developed here, this study also suggests the important role that FUS can have in efficient drug delivery via localized and transient BBB opening. PMID:27916657

  20. Real-time fMRI neurofeedback in adolescents with attention deficit hyperactivity disorder.

    PubMed

    Alegria, Analucia A; Wulff, Melanie; Brinson, Helen; Barker, Gareth J; Norman, Luke J; Brandeis, Daniel; Stahl, Daniel; David, Anthony S; Taylor, Eric; Giampietro, Vincent; Rubia, Katya

    2017-06-01

    Attention Deficit Hyperactivity Disorder (ADHD) is associated with poor self-control, underpinned by inferior fronto-striatal deficits. Real-time functional magnetic resonance neurofeedback (rtfMRI-NF) allows participants to gain self-control over dysregulated brain regions. Despite evidence for beneficial effects of electrophysiological-NF on ADHD symptoms, no study has applied the spatially superior rtfMRI-NF neurotherapy to ADHD. A randomized controlled trial tested the efficacy of rtfMRI-NF of right inferior prefrontal cortex (rIFG), a key region that is compromised in ADHD and upregulated with psychostimulants, on improvement of ADHD symptoms, cognition, and inhibitory fMRI activation. To control for region-specificity, an active control group received rtfMRI-NF of the left parahippocampal gyrus (lPHG). Thirty-one ADHD boys were randomly allocated and had to learn to upregulate their target brain region in an average of 11 rtfMRI-NF runs over 2 weeks. Feedback was provided through a video-clip of a rocket that had to be moved up into space. A transfer session without feedback tested learning retention as a proximal measure of transfer to everyday life. Both NF groups showed significant linear activation increases with increasing number of runs in their respective target regions and significant reduction in ADHD symptoms after neurotherapy and at 11-month follow-up. Only the group targeting rIFG, however, showed a transfer effect, which correlated with ADHD symptom reductions, improved at trend level in sustained attention, and showed increased IFG activation during an inhibitory fMRI task. This proof-of-concept study demonstrates for the first time feasibility, safety, and shorter- and longer-term efficacy of rtfMRI-NF of rIFG in adolescents with ADHD. Hum Brain Mapp 38:3190-3209, 2017. © 2017 The Authors Human Brain Mapping Published by Wiley Periodicals, Inc. © 2017 The Authors Human Brain Mapping Published by Wiley Periodicals, Inc.

  1. Quantitative Susceptibility Mapping using Structural Feature based Collaborative Reconstruction (SFCR) in the Human Brain

    PubMed Central

    Cai, Congbo; Chen, Zhong; van Zijl, Peter C.M.

    2017-01-01

    The reconstruction of MR quantitative susceptibility mapping (QSM) from local phase measurements is an ill posed inverse problem and different regularization strategies incorporating a priori information extracted from magnitude and phase images have been proposed. However, the anatomy observed in magnitude and phase images does not always coincide spatially with that in susceptibility maps, which could give erroneous estimation in the reconstructed susceptibility map. In this paper, we develop a structural feature based collaborative reconstruction (SFCR) method for QSM including both magnitude and susceptibility based information. The SFCR algorithm is composed of two consecutive steps corresponding to complementary reconstruction models, each with a structural feature based l1 norm constraint and a voxel fidelity based l2 norm constraint, which allows both the structure edges and tiny features to be recovered, whereas the noise and artifacts could be reduced. In the M-step, the initial susceptibility map is reconstructed by employing a k-space based compressed sensing model incorporating magnitude prior. In the S-step, the susceptibility map is fitted in spatial domain using weighted constraints derived from the initial susceptibility map from the M-step. Simulations and in vivo human experiments at 7T MRI show that the SFCR method provides high quality susceptibility maps with improved RMSE and MSSIM. Finally, the susceptibility values of deep gray matter are analyzed in multiple head positions, with the supine position most approximate to the gold standard COSMOS result. PMID:27019480

  2. Mapping of Brain Activity by Automated Volume Analysis of Immediate Early Genes.

    PubMed

    Renier, Nicolas; Adams, Eliza L; Kirst, Christoph; Wu, Zhuhao; Azevedo, Ricardo; Kohl, Johannes; Autry, Anita E; Kadiri, Lolahon; Umadevi Venkataraju, Kannan; Zhou, Yu; Wang, Victoria X; Tang, Cheuk Y; Olsen, Olav; Dulac, Catherine; Osten, Pavel; Tessier-Lavigne, Marc

    2016-06-16

    Understanding how neural information is processed in physiological and pathological states would benefit from precise detection, localization, and quantification of the activity of all neurons across the entire brain, which has not, to date, been achieved in the mammalian brain. We introduce a pipeline for high-speed acquisition of brain activity at cellular resolution through profiling immediate early gene expression using immunostaining and light-sheet fluorescence imaging, followed by automated mapping and analysis of activity by an open-source software program we term ClearMap. We validate the pipeline first by analysis of brain regions activated in response to haloperidol. Next, we report new cortical regions downstream of whisker-evoked sensory processing during active exploration. Last, we combine activity mapping with axon tracing to uncover new brain regions differentially activated during parenting behavior. This pipeline is widely applicable to different experimental paradigms, including animal species for which transgenic activity reporters are not readily available. Copyright © 2016 Elsevier Inc. All rights reserved.

  3. Mapping of brain activity by automated volume analysis of immediate early genes

    PubMed Central

    Renier, Nicolas; Adams, Eliza L.; Kirst, Christoph; Wu, Zhuhao; Azevedo, Ricardo; Kohl, Johannes; Autry, Anita E.; Kadiri, Lolahon; Venkataraju, Kannan Umadevi; Zhou, Yu; Wang, Victoria X.; Tang, Cheuk Y.; Olsen, Olav; Dulac, Catherine; Osten, Pavel; Tessier-Lavigne, Marc

    2016-01-01

    Summary Understanding how neural information is processed in physiological and pathological states would benefit from precise detection, localization and quantification of the activity of all neurons across the entire brain, which has not to date been achieved in the mammalian brain. We introduce a pipeline for high speed acquisition of brain activity at cellular resolution through profiling immediate early gene expression using immunostaining and light-sheet fluorescence imaging, followed by automated mapping and analysis of activity by an open-source software program we term ClearMap. We validate the pipeline first by analysis of brain regions activated in response to Haloperidol. Next, we report new cortical regions downstream of whisker-evoked sensory processing during active exploration. Lastly, we combine activity mapping with axon tracing to uncover new brain regions differentially activated during parenting behavior. This pipeline is widely applicable to different experimental paradigms, including animal species for which transgenic activity reporters are not readily available. PMID:27238021

  4. Mapping Informative Clusters in a Hierarchial Framework of fMRI Multivariate Analysis

    PubMed Central

    Xu, Rui; Zhen, Zonglei; Liu, Jia

    2010-01-01

    Pattern recognition methods have become increasingly popular in fMRI data analysis, which are powerful in discriminating between multi-voxel patterns of brain activities associated with different mental states. However, when they are used in functional brain mapping, the location of discriminative voxels varies significantly, raising difficulties in interpreting the locus of the effect. Here we proposed a hierarchical framework of multivariate approach that maps informative clusters rather than voxels to achieve reliable functional brain mapping without compromising the discriminative power. In particular, we first searched for local homogeneous clusters that consisted of voxels with similar response profiles. Then, a multi-voxel classifier was built for each cluster to extract discriminative information from the multi-voxel patterns. Finally, through multivariate ranking, outputs from the classifiers were served as a multi-cluster pattern to identify informative clusters by examining interactions among clusters. Results from both simulated and real fMRI data demonstrated that this hierarchical approach showed better performance in the robustness of functional brain mapping than traditional voxel-based multivariate methods. In addition, the mapped clusters were highly overlapped for two perceptually equivalent object categories, further confirming the validity of our approach. In short, the hierarchical framework of multivariate approach is suitable for both pattern classification and brain mapping in fMRI studies. PMID:21152081

  5. Mapping the Alzheimer’s Brain with Connectomics

    PubMed Central

    Xie, Teng; He, Yong

    2012-01-01

    Alzheimer’s disease (AD) is the most common form of dementia. As an incurable, progressive, and neurodegenerative disease, it causes cognitive and memory deficits. However, the biological mechanisms underlying the disease are not thoroughly understood. In recent years, non-invasive neuroimaging and neurophysiological techniques [e.g., structural magnetic resonance imaging (MRI), diffusion MRI, functional MRI, and EEG/MEG] and graph theory based network analysis have provided a new perspective on structural and functional connectivity patterns of the human brain (i.e., the human connectome) in health and disease. Using these powerful approaches, several recent studies of patients with AD exhibited abnormal topological organization in both global and regional properties of neuronal networks, indicating that AD not only affects specific brain regions, but also alters the structural and functional associations between distinct brain regions. Specifically, disruptive organization in the whole-brain networks in AD is involved in the loss of small-world characters and the re-organization of hub distributions. These aberrant neuronal connectivity patterns were associated with cognitive deficits in patients with AD, even with genetic factors in healthy aging. These studies provide empirical evidence to support the existence of an aberrant connectome of AD. In this review we will summarize recent advances discovered in large-scale brain network studies of AD, mainly focusing on graph theoretical analysis of brain connectivity abnormalities. These studies provide novel insights into the pathophysiological mechanisms of AD and could be helpful in developing imaging biomarkers for disease diagnosis and monitoring. PMID:22291664

  6. Edge Density Imaging: Mapping the Anatomic Embedding of the Structural Connectome Within the White Matter of the Human Brain

    PubMed Central

    Owen, Julia P.; Chang, Yi-Shin; Mukherjee, Pratik

    2015-01-01

    The structural connectome has emerged as a powerful tool to characterize the network architecture of the human brain and shows great potential for generating important new biomarkers for neurologic and psychiatric disorders. The edges of the cerebral graph traverse white matter to interconnect cortical and subcortical nodes, although the anatomic embedding of these edges is generally overlooked in the literature. Mapping the paths of the connectome edges could elucidate the relative importance of individual white matter tracts to the overall network topology of the brain and also lead to a better understanding of the effect of regionally-specific white matter pathology on cognition and behavior. In this work, we introduce edge density imaging (EDI), which maps the number of network edges that pass through every white matter voxel. Test-retest analysis shows good to excellent reliability for edge density (ED) measurements, with consistent results using different cortical and subcortical parcellation schemes and different diffusion MR imaging acquisition parameters. We also demonstrate that ED yields complementary information to both traditional and emerging voxel-wise metrics of white matter microstructure and connectivity, including fractional anisotropy, track density, fiber orientation dispersion and neurite density. Our results demonstrate spatially ordered variations of ED throughout the white matter, notably including greater ED in posterior than anterior cerebral white matter. The EDI framework is employed to map the white matter regions that are enriched with pathways connecting rich club nodes and also those with high densities of intra-modular and inter-modular edges. We show that periventricular white matter has particularly high ED and high densities of rich club edges, which is significant for diseases in which these areas are selectively affected, ranging from white matter injury of prematurity in infants to leukoaraiosis in the elderly. Using edge betweenness centrality, we identify specific white matter regions involved in a large number of shortest paths, some containing highly connected rich club edges while others are relatively isolated within individual modules. Overall, these findings reveal an intricate relationship between white matter anatomy and the structural connectome, motivating further exploration of EDI for biomarkers of cognition and behavior. PMID:25592996

  7. Effect of Experimental Thyrotoxicosis on Brain Gray Matter: A Voxel-Based Morphometry Study.

    PubMed

    Göbel, Anna; Heldmann, Marcus; Göttlich, Martin; Dirk, Anna-Luise; Brabant, Georg; Münte, Thomas F

    2015-09-01

    Hyper-as well hypothyroidism have an effect on behavior and brain function. Moreover, during development thyroid hormones influence brain structure. This study aimed to demonstrate an effect of experimentally induced hyperthyroidism on brain gray matter in healthy adult humans. High-resolution 3D T1-weighted images were acquired in 29 healthy young subjects prior to as well as after receiving 250 µg of T4 per day for 8 weeks. Voxel-based morphometry analysis was performed using Statistical Parametric Mapping 8 (SPM8). Laboratory testing confirmed the induction of hyperthyroidism. In the hyperthyroid condition, gray matter volumes were increased in the right posterior cerebellum (lobule VI) and decreased in the bilateral visual cortex and anterior cerebellum (lobules I-IV) compared to the euthyroid condition. Our study provides evidence that short periods of hyperthyroidism induce distinct alterations in brain structures of cerebellar regions that have been associated with sensorimotor functions as well as working memory in the literature.

  8. Focused ultrasound delivery of Raman nanoparticles across the blood-brain barrier: Potential for targeting experimental brain tumors

    PubMed Central

    Diaz, Roberto Jose; McVeigh, Patrick Z.; O’Reilly, Meaghan A.; Burrell, Kelly; Bebenek, Matthew; Smith, Christian; Etame, Arnold; Zadeh, Gelareh; Hynynen, Kullervo; Wilson, Brian C.; Rutka, James T.

    2014-01-01

    Spectral mapping of nanoparticles with surface enhanced Raman scattering (SERS) capability in the near-infrared range is an emerging molecular imaging technique. We used magnetic resonance image-guided transcranial focused ultrasound (TcMRgFUS) to reversibly disrupt the blood-brain barrier (BBB) adjacent to brain tumor margins in rats. Glioma cells were found to internalize SERS capable nanoparticles of 50 nm or 120 nm physical diameter. Surface coating with anti-epidermal growth factor receptor antibody or non-specific human immunoglobulin G, resulted in enhanced cell uptake of nanoparticles in-vitro compared to nanoparticles with methyl terminated 12-unit polyethylene glycol surface. BBB disruption permitted the delivery of SERS capable spherical 50 or 120 nm gold nanoparticles to the tumor margins. Thus, nanoparticles with SERS imaging capability can be delivered across the BBB non-invasively using TcMRgFUS and have the potential to be used as optical tracking agents at the invasive front of malignant brain tumors. PMID:24374363

  9. Specificities of Awake Craniotomy and Brain Mapping in Children for Resection of Supratentorial Tumors in the Language Area.

    PubMed

    Delion, Matthieu; Terminassian, Aram; Lehousse, Thierry; Aubin, Ghislaine; Malka, Jean; N'Guyen, Sylvie; Mercier, Philippe; Menei, Philippe

    2015-12-01

    In the pediatric population, awake craniotomy began to be used for the resection of brain tumor located close to eloquent areas. Some specificities must be taken into account to adapt this method to children. The aim of this clinical study is to not only confirm the feasibility of awake craniotomy and language brain mapping in the pediatric population but also identify the specificities and necessary adaptations of the procedure. Six children aged 11 to 16 were operated on while awake under local anesthesia with language brain mapping for supratentorial brain lesions (tumor and cavernoma). The preoperative planning comprised functional magnetic resonance imaging (MRI) and neuropsychologic and psychologic assessment. The specific preoperative preparation is clearly explained including hypnosis conditioning and psychiatric evaluation. The success of the procedure was based on the ability to perform the language brain mapping and the tumor removal without putting the patient to sleep. We investigated the pediatric specificities, psychological experience, and neuropsychologic follow-up. The children experienced little anxiety, probably in large part due to the use of hypnosis. We succeeded in doing the cortical-subcortical mapping and removing the tumor without putting the patient to sleep in all cases. The psychological experience was good, and the neuropsychologic follow-up showed a favorable evolution. Preoperative preparation and hypnosis in children seemed important for performing awake craniotomy and contributing language brain mapping with the best possible psychological experience. The pediatrics specificities are discussed. Copyright © 2015 Elsevier Inc. All rights reserved.

  10. The Application of MRI for Depiction of Subtle Blood Brain Barrier Disruption in Stroke

    PubMed Central

    Israeli, David; Tanne, David; Daniels, Dianne; Last, David; Shneor, Ran; Guez, David; Landau, Efrat; Roth, Yiftach; Ocherashvilli, Aharon; Bakon, Mati; Hoffman, Chen; Weinberg, Amit; Volk, Talila; Mardor, Yael

    2011-01-01

    The development of imaging methodologies for detecting blood-brain-barrier (BBB) disruption may help predict stroke patient's propensity to develop hemorrhagic complications following reperfusion. We have developed a delayed contrast extravasation MRI-based methodology enabling real-time depiction of subtle BBB abnormalities in humans with high sensitivity to BBB disruption and high spatial resolution. The increased sensitivity to subtle BBB disruption is obtained by acquiring T1-weighted MRI at relatively long delays (~15 minutes) after contrast injection and subtracting from them images acquired immediately after contrast administration. In addition, the relatively long delays allow for acquisition of high resolution images resulting in high resolution BBB disruption maps. The sensitivity is further increased by image preprocessing with corrections for intensity variations and with whole body (rigid+elastic) registration. Since only two separate time points are required, the time between the two acquisitions can be used for acquiring routine clinical data, keeping the total imaging time to a minimum. A proof of concept study was performed in 34 patients with ischemic stroke and 2 patients with brain metastases undergoing high resolution T1-weighted MRI acquired at 3 time points after contrast injection. The MR images were pre-processed and subtracted to produce BBB disruption maps. BBB maps of patients with brain metastases and ischemic stroke presented different patterns of BBB opening. The significant advantage of the long extravasation time was demonstrated by a dynamic-contrast-enhancement study performed continuously for 18 min. The high sensitivity of our methodology enabled depiction of clear BBB disruption in 27% of the stroke patients who did not have abnormalities on conventional contrast-enhanced MRI. In 36% of the patients, who had abnormalities detectable by conventional MRI, the BBB disruption volumes were significantly larger in the maps than in conventional MRI. These results demonstrate the advantages of delayed contrast extravasation in increasing the sensitivity to subtle BBB disruption in ischemic stroke patients. The calculated disruption maps provide clear depiction of significant volumes of BBB disruption unattainable by conventional contrast-enhanced MRI. PMID:21209786

  11. The application of MRI for depiction of subtle blood brain barrier disruption in stroke.

    PubMed

    Israeli, David; Tanne, David; Daniels, Dianne; Last, David; Shneor, Ran; Guez, David; Landau, Efrat; Roth, Yiftach; Ocherashvilli, Aharon; Bakon, Mati; Hoffman, Chen; Weinberg, Amit; Volk, Talila; Mardor, Yael

    2010-12-26

    The development of imaging methodologies for detecting blood-brain-barrier (BBB) disruption may help predict stroke patient's propensity to develop hemorrhagic complications following reperfusion. We have developed a delayed contrast extravasation MRI-based methodology enabling real-time depiction of subtle BBB abnormalities in humans with high sensitivity to BBB disruption and high spatial resolution. The increased sensitivity to subtle BBB disruption is obtained by acquiring T1-weighted MRI at relatively long delays (~15 minutes) after contrast injection and subtracting from them images acquired immediately after contrast administration. In addition, the relatively long delays allow for acquisition of high resolution images resulting in high resolution BBB disruption maps. The sensitivity is further increased by image preprocessing with corrections for intensity variations and with whole body (rigid+elastic) registration. Since only two separate time points are required, the time between the two acquisitions can be used for acquiring routine clinical data, keeping the total imaging time to a minimum. A proof of concept study was performed in 34 patients with ischemic stroke and 2 patients with brain metastases undergoing high resolution T1-weighted MRI acquired at 3 time points after contrast injection. The MR images were pre-processed and subtracted to produce BBB disruption maps. BBB maps of patients with brain metastases and ischemic stroke presented different patterns of BBB opening. The significant advantage of the long extravasation time was demonstrated by a dynamic-contrast-enhancement study performed continuously for 18 min. The high sensitivity of our methodology enabled depiction of clear BBB disruption in 27% of the stroke patients who did not have abnormalities on conventional contrast-enhanced MRI. In 36% of the patients, who had abnormalities detectable by conventional MRI, the BBB disruption volumes were significantly larger in the maps than in conventional MRI. These results demonstrate the advantages of delayed contrast extravasation in increasing the sensitivity to subtle BBB disruption in ischemic stroke patients. The calculated disruption maps provide clear depiction of significant volumes of BBB disruption unattainable by conventional contrast-enhanced MRI.

  12. Neural correlates of spatial and nonspatial attention determined using intracranial electroencephalographic signals in humans

    PubMed Central

    Park, Ga Young; Kim, Taekyung; Park, Jinsick; Lee, Eun Mi; Ryu, Han Uk; Kim, Sun I.; Kim, In Young; Husain, Masud

    2016-01-01

    Abstract Few studies have directly compared the neural correlates of spatial attention (i.e., attention to a particular location) and nonspatial attention (i.e., attention to a feature in the visual scene) using well‐controlled tasks. Here, we investigated the neural correlates of spatial and nonspatial attention in humans using intracranial electroencephalography. The topography and number of electrodes showing significant event‐related desynchronization (ERD) or event‐related synchronization (ERS) in different frequency bands were studied in 13 epileptic patients. Performance was not significantly different between the two conditions. In both conditions, ERD in the low‐frequency bands and ERS in the high‐frequency bands were present bilaterally in the parietal cortex (prominently on the right hemisphere) and frontal regions. In addition to these common changes, spatial attention involved right‐lateralized activity that was maximal in the right superior parietal lobule (SPL), whereas nonspatial attention involved wider brain networks including the bilateral parietal, frontal, and temporal regions, but still had maximal activity in the right parietal lobe. Within the parietal lobe, spatial attention involved ERD or ERS in the right SPL, whereas nonspatial attention involved ERD or ERS in the right inferior parietal lobule. These findings reveal that common as well as different brain networks are engaged in spatial and nonspatial attention. Hum Brain Mapp 37:3041–3054, 2016. © 2016 The Authors Human Brain Mapping Published by Wiley Periodicals, Inc. PMID:27125904

  13. Automatic segmentation of brain MRIs and mapping neuroanatomy across the human lifespan

    NASA Astrophysics Data System (ADS)

    Keihaninejad, Shiva; Heckemann, Rolf A.; Gousias, Ioannis S.; Rueckert, Daniel; Aljabar, Paul; Hajnal, Joseph V.; Hammers, Alexander

    2009-02-01

    A robust model for the automatic segmentation of human brain images into anatomically defined regions across the human lifespan would be highly desirable, but such structural segmentations of brain MRI are challenging due to age-related changes. We have developed a new method, based on established algorithms for automatic segmentation of young adults' brains. We used prior information from 30 anatomical atlases, which had been manually segmented into 83 anatomical structures. Target MRIs came from 80 subjects (~12 individuals/decade) from 20 to 90 years, with equal numbers of men, women; data from two different scanners (1.5T, 3T), using the IXI database. Each of the adult atlases was registered to each target MR image. By using additional information from segmentation into tissue classes (GM, WM and CSF) to initialise the warping based on label consistency similarity before feeding this into the previous normalised mutual information non-rigid registration, the registration became robust enough to accommodate atrophy and ventricular enlargement with age. The final segmentation was obtained by combination of the 30 propagated atlases using decision fusion. Kernel smoothing was used for modelling the structural volume changes with aging. Example linear correlation coefficients with age were, for lateral ventricular volume, rmale=0.76, rfemale=0.58 and, for hippocampal volume, rmale=-0.6, rfemale=-0.4 (allρ<0.01).

  14. Validation of brain-derived signals in near-infrared spectroscopy through multivoxel analysis of concurrent functional magnetic resonance imaging.

    PubMed

    Moriguchi, Yoshiya; Noda, Takamasa; Nakayashiki, Kosei; Takata, Yohei; Setoyama, Shiori; Kawasaki, Shingo; Kunisato, Yoshihiko; Mishima, Kazuo; Nakagome, Kazuyuki; Hanakawa, Takashi

    2017-10-01

    Near-infrared spectroscopy (NIRS) is a convenient and safe brain-mapping tool. However, its inevitable confounding with hemodynamic responses outside the brain, especially in the frontotemporal head, has questioned its validity. Some researchers attempted to validate NIRS signals through concurrent measurements with functional magnetic resonance imaging (fMRI), but, counterintuitively, NIRS signals rarely correlate with local fMRI signals in NIRS channels, although both mapping techniques should measure the same hemoglobin concentration. Here, we tested a novel hypothesis that different voxels within the scalp and the brain tissues might have substantially different hemoglobin absorption rates of near-infrared light, which might differentially contribute to NIRS signals across channels. Therefore, we newly applied a multivariate approach, a partial least squares regression, to explain NIRS signals with multivoxel information from fMRI within the brain and soft tissues in the head. We concurrently obtained fMRI and NIRS signals in 9 healthy human subjects engaging in an n-back task. The multivariate fMRI model was quite successfully able to predict the NIRS signals by cross-validation (interclass correlation coefficient = ∼0.85). This result confirmed that fMRI and NIRS surely measure the same hemoglobin concentration. Additional application of Monte-Carlo permutation tests confirmed that the model surely reflects temporal and spatial hemodynamic information, not random noise. After this thorough validation, we calculated the ratios of the contributions of the brain and soft-tissue hemodynamics to the NIRS signals, and found that the contribution ratios were quite different across different NIRS channels in reality, presumably because of the structural complexity of the frontotemporal regions. Hum Brain Mapp 38:5274-5291, 2017. © 2017 Wiley Periodicals, Inc. © 2017 Wiley Periodicals, Inc.

  15. Forthergillian Lecture. Imaging human brain function.

    PubMed

    Frackowiak, R S

    The non-invasive brain scanning techniques introduced a quarter of a century ago have become crucial for diagnosis in clinical neurology. They have also been used to investigate brain function and have provided information about normal activity and pathogenesis. They have been used to investigate functional specialization in the brain and how specialized areas communicate to generate complex integrated functions such as speech, memory, the emotions and so on. The phenomenon of brain plasticity is poorly understood and yet clinical neurologists are aware, from everyday observations, that spontaneous recovery from brain lesions is common. An improved understanding of the mechanisms of recovery may generate new therapeutic strategies and indicate ways of modulating mechanisms that promote plastic compensation for loss of function. The main methods used to investigate these issues are positron emission tomography and magnetic resonance imaging (M.R.I.). M.R.I. is also used to map brain structure. The techniques of functional brain mapping and computational morphometrics depend on high performance scanners and a validated set of analytic statistical procedures that generate reproducible data and meaningful inferences from brain scanning data. The motor system presents a good paradigm to illustrate advances made by scanning towards an understanding of plasticity at the level of brain areas. The normal motor system is organized in a nested hierarchy. Recovery from paralysis caused by internal capsule strokes involves functional reorganization manifesting itself as changed patterns of activity in the component brain areas of the normal motor system. The pattern of plastic modification depends in part on patterns of residual or disturbed connectivity after brain injury. Therapeutic manipulations in patients with Parkinson's disease using deep brain stimulation, dopaminergic agents or fetal mesencephalic transplantation provide a means to examine mechanisms underpinning plastic change. Other models of plastic change, such as normal visuospatial learning or re-establishing speech comprehension after cochlear implantation in the deaf illustrate how patterns of brain function adapt over time. Limitations of the scanning techniques and prospects for the future are discussed in relation to new developments in the neuroimaging field.

  16. Importance of extended spatial coverage for quantitative susceptibility mapping of iron-rich deep gray matter.

    PubMed

    Elkady, Ahmed M; Sun, Hongfu; Wilman, Alan H

    2016-05-01

    Quantitative Susceptibility Mapping (QSM) is an emerging area of brain research with clear application to brain iron studies in deep gray matter. However, acquisition of standard whole brain QSM can be time-consuming. One means to reduce scan time is to use a focal acquisition restricted only to the regions of interest such as deep gray matter. However, the non-local dipole field necessary for QSM reconstruction extends far beyond the structure of interest. We demonstrate the practical implications of these non-local fields on the choice of brain volume for QSM. In an illustrative numerical simulation and then in human brain experiments, we examine the effect on QSM of volume reduction in each dimension. For the globus pallidus, as an example of iron-rich deep gray matter, we demonstrate that substantial errors can arise even when the field-of-view far exceeds the physical structural boundaries. Thus, QSM reconstruction requires a non-local field-of-view prescription to ensure minimal errors. An axial QSM acquisition, centered on the globus pallidus, should encompass at least 76mm in the superior-inferior direction to conserve susceptibility values from the globus pallidus. This dimension exceeds the physical coronal extent of this structure by at least five-fold. As QSM sees wider use in the neuroscience community, its unique requirement for an extended field-of-view needs to be considered. Copyright © 2016 Elsevier Inc. All rights reserved.

  17. Human parietofrontal networks related to action observation detected at rest.

    PubMed

    Molinari, Elisa; Baraldi, Patrizia; Campanella, Martina; Duzzi, Davide; Nocetti, Luca; Pagnoni, Giuseppe; Porro, Carlo A

    2013-01-01

    Recent data show a broad correspondence between human resting-state and task-related brain networks. We performed a functional magnetic resonance imaging (fMRI) study to compare, in the same subjects, the spatial independent component analysis (ICA) maps obtained at rest and during the observation of either reaching/grasping hand actions or matching static pictures. Two parietofrontal networks were identified by ICA from action observation task data. One network, specific to reaching/grasping observation, included portions of the anterior intraparietal cortex and of the dorsal and ventral lateral premotor cortices. A second network included more posterior portions of the parietal lobe, the dorsomedial frontal cortex, and more anterior and ventral parts, respectively, of the dorsal and ventral premotor cortices, extending toward Broca's area; this network was more generally related to the observation of hand action and static pictures. A good spatial correspondence was found between the 2 observation-related ICA maps and 2 ICA maps identified from resting-state data. The anatomical connectivity among the identified clusters was tested in the same volunteers, using persistent angular structure-MRI and deterministic tractography. These findings extend available knowledge of human parietofrontal circuits and further support the hypothesis of a persistent coherence within functionally relevant networks during rest.

  18. Detecting large-scale networks in the human brain using high-density electroencephalography.

    PubMed

    Liu, Quanying; Farahibozorg, Seyedehrezvan; Porcaro, Camillo; Wenderoth, Nicole; Mantini, Dante

    2017-09-01

    High-density electroencephalography (hdEEG) is an emerging brain imaging technique that can be used to investigate fast dynamics of electrical activity in the healthy and the diseased human brain. Its applications are however currently limited by a number of methodological issues, among which the difficulty in obtaining accurate source localizations. In particular, these issues have so far prevented EEG studies from reporting brain networks similar to those previously detected by functional magnetic resonance imaging (fMRI). Here, we report for the first time a robust detection of brain networks from resting state (256-channel) hdEEG recordings. Specifically, we obtained 14 networks previously described in fMRI studies by means of realistic 12-layer head models and exact low-resolution brain electromagnetic tomography (eLORETA) source localization, together with independent component analysis (ICA) for functional connectivity analysis. Our analyses revealed three important methodological aspects. First, brain network reconstruction can be improved by performing source localization using the gray matter as source space, instead of the whole brain. Second, conducting EEG connectivity analyses in individual space rather than on concatenated datasets may be preferable, as it permits to incorporate realistic information on head modeling and electrode positioning. Third, the use of a wide frequency band leads to an unbiased and generally accurate reconstruction of several network maps, whereas filtering data in a narrow frequency band may enhance the detection of specific networks and penalize that of others. We hope that our methodological work will contribute to rise of hdEEG as a powerful tool for brain research. Hum Brain Mapp 38:4631-4643, 2017. © 2017 Wiley Periodicals, Inc. © 2017 Wiley Periodicals, Inc.

  19. Operant conditioning of a multiple degree-of-freedom brain-machine interface in a primate model of amputation.

    PubMed

    Balasubramanian, Karthikeyan; Southerland, Joshua; Vaidya, Mukta; Qian, Kai; Eleryan, Ahmed; Fagg, Andrew H; Sluzky, Marc; Oweiss, Karim; Hatsopoulos, Nicholas

    2013-01-01

    Operant conditioning with biofeedback has been shown to be an effective method to modify neural activity to generate goal-directed actions in a brain-machine interface. It is particularly useful when neural activity cannot be mathematically mapped to motor actions of the actual body such as in the case of amputation. Here, we implement an operant conditioning approach with visual feedback in which an amputated monkey is trained to control a multiple degree-of-freedom robot to perform a reach-to-grasp behavior. A key innovation is that each controlled dimension represents a behaviorally relevant synergy among a set of joint degrees-of-freedom. We present a number of behavioral metrics by which to assess improvements in BMI control with exposure to the system. The use of non-human primates with chronic amputation is arguably the most clinically-relevant model of human amputation that could have direct implications for developing a neural prosthesis to treat humans with missing upper limbs.

  20. Sensing Super-Position: Human Sensing Beyond the Visual Spectrum

    NASA Technical Reports Server (NTRS)

    Maluf, David A.; Schipper, John F.

    2007-01-01

    The coming decade of fast, cheap and miniaturized electronics and sensory devices opens new pathways for the development of sophisticated equipment to overcome limitations of the human senses. This paper addresses the technical feasibility of augmenting human vision through Sensing Super-position by mixing natural Human sensing. The current implementation of the device translates visual and other passive or active sensory instruments into sounds, which become relevant when the visual resolution is insufficient for very difficult and particular sensing tasks. A successful Sensing Super-position meets many human and pilot vehicle system requirements. The system can be further developed into cheap, portable, and low power taking into account the limited capabilities of the human user as well as the typical characteristics of his dynamic environment. The system operates in real time, giving the desired information for the particular augmented sensing tasks. The Sensing Super-position device increases the image resolution perception and is obtained via an auditory representation as well as the visual representation. Auditory mapping is performed to distribute an image in time. The three-dimensional spatial brightness and multi-spectral maps of a sensed image are processed using real-time image processing techniques (e.g. histogram normalization) and transformed into a two-dimensional map of an audio signal as a function of frequency and time. This paper details the approach of developing Sensing Super-position systems as a way to augment the human vision system by exploiting the capabilities of Lie human hearing system as an additional neural input. The human hearing system is capable of learning to process and interpret extremely complicated and rapidly changing auditory patterns. The known capabilities of the human hearing system to learn and understand complicated auditory patterns provided the basic motivation for developing an image-to-sound mapping system. The human brain is superior to most existing computer systems in rapidly extracting relevant information from blurred, noisy, and redundant images. From a theoretical viewpoint, this means that the available bandwidth is not exploited in an optimal way. While image-processing techniques can manipulate, condense and focus the information (e.g., Fourier Transforms), keeping the mapping as direct and simple as possible might also reduce the risk of accidentally filtering out important clues. After all, especially a perfect non-redundant sound representation is prone to loss of relevant information in the non-perfect human hearing system. Also, a complicated non-redundant image-to-sound mapping may well be far more difficult to learn and comprehend than a straightforward mapping, while the mapping system would increase in complexity and cost. This work will demonstrate some basic information processing for optimal information capture for headmounted systems.

  1. Evidence for hysteresis in the cerebral pressure-flow relationship in healthy men.

    PubMed

    Brassard, Patrice; Ferland-Dutil, Hélène; Smirl, Jonathan D; Paquette, Myriam; Le Blanc, Olivier; Malenfant, Simon; Ainslie, Philip N

    2017-04-01

    The cerebrovasculature is more efficient at compensating for pharmacologically induced transient hypertension versus transient hypotension. Whether this phenomenon exists during nonpharmacologically induced hypertension and hypotension is currently unknown. We compared the percent change in mean velocity in the middle cerebral artery (MCAvmean) per percent change in mean arterial pressure (MAP) (%ΔMCAVmean/%ΔMAP) during transient hypertension and hypotension induced during squat-stand maneuvers performed at 0.05 Hz (20-s cycles) and 0.10 Hz (10-s cycles) in 58 male volunteers. %ΔMCAvmean/%ΔMAP was attenuated by 25% ( P = 0.03, 0.05 Hz) and 47% ( P < 0.0001, 0.10 Hz) during transient hypertension versus hypotension. Thus, these findings indicate that the brain in healthy men is better adapted to compensate for physiologically relevant transient hypertension than hypotension. NEW & NOTEWORTHY The novel finding of this study is that the change in middle cerebral artery mean flow velocity is attenuated during hypertension compared with hypotension physiologically induced by oscillations in blood pressure in men. These results support that the human brain is more effective at compensating for transient hypertension than hypotension. Copyright © 2017 the American Physiological Society.

  2. High-cost, high-capacity backbone for global brain communication.

    PubMed

    van den Heuvel, Martijn P; Kahn, René S; Goñi, Joaquín; Sporns, Olaf

    2012-07-10

    Network studies of human brain structural connectivity have identified a specific set of brain regions that are both highly connected and highly central. Recent analyses have shown that these putative hub regions are mutually and densely interconnected, forming a "rich club" within the human brain. Here we show that the set of pathways linking rich club regions forms a central high-cost, high-capacity backbone for global brain communication. Diffusion tensor imaging (DTI) data of two sets of 40 healthy subjects were used to map structural brain networks. The contributions to network cost and communication capacity of global cortico-cortical connections were assessed through measures of their topology and spatial embedding. Rich club connections were found to be more costly than predicted by their density alone and accounted for 40% of the total communication cost. Furthermore, 69% of all minimally short paths between node pairs were found to travel through the rich club and a large proportion of these communication paths consisted of ordered sequences of edges ("path motifs") that first fed into, then traversed, and finally exited the rich club, while passing through nodes of increasing and then decreasing degree. The prevalence of short paths that follow such ordered degree sequences suggests that neural communication might take advantage of strategies for dynamic routing of information between brain regions, with an important role for a highly central rich club. Taken together, our results show that rich club connections make an important contribution to interregional signal traffic, forming a central high-cost, high-capacity backbone for global brain communication.

  3. Mapping Language Function in the Brain: A Review of the Recent Literature.

    ERIC Educational Resources Information Center

    Crafton, Robert E.; Kido, Elissa

    2000-01-01

    Considers the potential importance of brain study for composition instruction, briefly describes functional imaging techniques, and reviews the findings of recent brain-mapping studies investigating the neurocognitive systems involved in language function. Presents a review of the recent literature and considers the possible implications of this…

  4. Comparing consistency of R2* and T2*-weighted BOLD analysis of resting state fetal fMRI

    NASA Astrophysics Data System (ADS)

    Seshamani, Sharmishtaa; Blazejewska, Anna I.; Gatenby, Christopher; Mckown, Susan; Caucutt, Jason; Dighe, Manjiri; Studholme, Colin

    2015-03-01

    Understanding when and how resting state brain functional activity begins in the human brain is an increasing area of interest in both basic neuroscience and in the clinical evaluation of the brain during pregnancy and after premature birth. Although fMRI studies have been carried out on pregnant women since the 1990's, reliable mapping of brain function in utero is an extremely challenging problem due to the unconstrained fetal head motion. Recent studies have employed scrubbing to exclude parts of the time series and whole subjects from studies in order to control the confounds of motion. Fundamentally, even after correction of the location of signals due to motion, signal intensity variations are a fundamental limitation, due to coil sensitivity and spin history effects. An alternative technique is to use a more parametric MRI signal derived from multiple echoes that provides a level of independence from basic MRI signal variation. Here we examine the use of R2* mapping combined with slice based multi echo geometric distortion correction for in-utero studies. The challenges for R2* mapping arise from the relatively low signal strength of in-utero data. In this paper we focus on comparing activation detection in-utero using T2W and R2* approaches. We make use a subset of studies with relatively limited motion to compare the activation patterns without the additional confound of significant motion. Results at different gestational ages indicate comparable agreement in many activation patterns when limited motion is present, and the detection of some additional networks in the R2* data, not seen in the T2W results.

  5. Imaging of neural oscillations with embedded inferential and group prevalence statistics.

    PubMed

    Donhauser, Peter W; Florin, Esther; Baillet, Sylvain

    2018-02-01

    Magnetoencephalography and electroencephalography (MEG, EEG) are essential techniques for studying distributed signal dynamics in the human brain. In particular, the functional role of neural oscillations remains to be clarified. For that reason, imaging methods need to identify distinct brain regions that concurrently generate oscillatory activity, with adequate separation in space and time. Yet, spatial smearing and inhomogeneous signal-to-noise are challenging factors to source reconstruction from external sensor data. The detection of weak sources in the presence of stronger regional activity nearby is a typical complication of MEG/EEG source imaging. We propose a novel, hypothesis-driven source reconstruction approach to address these methodological challenges. The imaging with embedded statistics (iES) method is a subspace scanning technique that constrains the mapping problem to the actual experimental design. A major benefit is that, regardless of signal strength, the contributions from all oscillatory sources, which activity is consistent with the tested hypothesis, are equalized in the statistical maps produced. We present extensive evaluations of iES on group MEG data, for mapping 1) induced oscillations using experimental contrasts, 2) ongoing narrow-band oscillations in the resting-state, 3) co-modulation of brain-wide oscillatory power with a seed region, and 4) co-modulation of oscillatory power with peripheral signals (pupil dilation). Along the way, we demonstrate several advantages of iES over standard source imaging approaches. These include the detection of oscillatory coupling without rejection of zero-phase coupling, and detection of ongoing oscillations in deeper brain regions, where signal-to-noise conditions are unfavorable. We also show that iES provides a separate evaluation of oscillatory synchronization and desynchronization in experimental contrasts, which has important statistical advantages. The flexibility of iES allows it to be adjusted to many experimental questions in systems neuroscience.

  6. Electrophysiological correlates of the BOLD signal for EEG-informed fMRI

    PubMed Central

    Murta, Teresa; Leite, Marco; Carmichael, David W; Figueiredo, Patrícia; Lemieux, Louis

    2015-01-01

    Electroencephalography (EEG) and functional magnetic resonance imaging (fMRI) are important tools in cognitive and clinical neuroscience. Combined EEG–fMRI has been shown to help to characterise brain networks involved in epileptic activity, as well as in different sensory, motor and cognitive functions. A good understanding of the electrophysiological correlates of the blood oxygen level-dependent (BOLD) signal is necessary to interpret fMRI maps, particularly when obtained in combination with EEG. We review the current understanding of electrophysiological–haemodynamic correlates, during different types of brain activity. We start by describing the basic mechanisms underlying EEG and BOLD signals and proceed by reviewing EEG-informed fMRI studies using fMRI to map specific EEG phenomena over the entire brain (EEG–fMRI mapping), or exploring a range of EEG-derived quantities to determine which best explain colocalised BOLD fluctuations (local EEG–fMRI coupling). While reviewing studies of different forms of brain activity (epileptic and nonepileptic spontaneous activity; cognitive, sensory and motor functions), a significant attention is given to epilepsy because the investigation of its haemodynamic correlates is the most common application of EEG-informed fMRI. Our review is focused on EEG-informed fMRI, an asymmetric approach of data integration. We give special attention to the invasiveness of electrophysiological measurements and the simultaneity of multimodal acquisitions because these methodological aspects determine the nature of the conclusions that can be drawn from EEG-informed fMRI studies. We emphasise the advantages of, and need for, simultaneous intracranial EEG–fMRI studies in humans, which recently became available and hold great potential to improve our understanding of the electrophysiological correlates of BOLD fluctuations. PMID:25277370

  7. Imaging of neural oscillations with embedded inferential and group prevalence statistics

    PubMed Central

    2018-01-01

    Magnetoencephalography and electroencephalography (MEG, EEG) are essential techniques for studying distributed signal dynamics in the human brain. In particular, the functional role of neural oscillations remains to be clarified. For that reason, imaging methods need to identify distinct brain regions that concurrently generate oscillatory activity, with adequate separation in space and time. Yet, spatial smearing and inhomogeneous signal-to-noise are challenging factors to source reconstruction from external sensor data. The detection of weak sources in the presence of stronger regional activity nearby is a typical complication of MEG/EEG source imaging. We propose a novel, hypothesis-driven source reconstruction approach to address these methodological challenges. The imaging with embedded statistics (iES) method is a subspace scanning technique that constrains the mapping problem to the actual experimental design. A major benefit is that, regardless of signal strength, the contributions from all oscillatory sources, which activity is consistent with the tested hypothesis, are equalized in the statistical maps produced. We present extensive evaluations of iES on group MEG data, for mapping 1) induced oscillations using experimental contrasts, 2) ongoing narrow-band oscillations in the resting-state, 3) co-modulation of brain-wide oscillatory power with a seed region, and 4) co-modulation of oscillatory power with peripheral signals (pupil dilation). Along the way, we demonstrate several advantages of iES over standard source imaging approaches. These include the detection of oscillatory coupling without rejection of zero-phase coupling, and detection of ongoing oscillations in deeper brain regions, where signal-to-noise conditions are unfavorable. We also show that iES provides a separate evaluation of oscillatory synchronization and desynchronization in experimental contrasts, which has important statistical advantages. The flexibility of iES allows it to be adjusted to many experimental questions in systems neuroscience. PMID:29408902

  8. Functional MRI mapping of visual function and selective attention for performance assessment and presurgical planning using conjunctive visual search

    PubMed Central

    Parker, Jason G; Zalusky, Eric J; Kirbas, Cemil

    2014-01-01

    Background Accurate mapping of visual function and selective attention using fMRI is important in the study of human performance as well as in presurgical treatment planning of lesions in or near visual centers of the brain. Conjunctive visual search (CVS) is a useful tool for mapping visual function during fMRI because of its greater activation extent compared with high-capacity parallel search processes. Aims The purpose of this work was to develop and evaluate a CVS that was capable of generating consistent activation in the basic and higher level visual areas of the brain by using a high number of distractors as well as an optimized contrast condition. Materials and methods Images from 10 healthy volunteers were analyzed and brain regions of greatest activation and deactivation were determined using a nonbiased decomposition of the results at the hemisphere, lobe, and gyrus levels. The results were quantified in terms of activation and deactivation extent and mean z-statistic. Results The proposed CVS was found to generate robust activation of the occipital lobe, as well as regions in the middle frontal gyrus associated with coordinating eye movements and in regions of the insula associated with task-level control and focal attention. As expected, the task demonstrated deactivation patterns commonly implicated in the default-mode network. Further deactivation was noted in the posterior region of the cerebellum, most likely associated with the formation of optimal search strategy. Conclusion We believe the task will be useful in studies of visual and selective attention in the neuroscience community as well as in mapping visual function in clinical fMRI. PMID:24683515

  9. Brain tumor segmentation in multi-spectral MRI using convolutional neural networks (CNN).

    PubMed

    Iqbal, Sajid; Ghani, M Usman; Saba, Tanzila; Rehman, Amjad

    2018-04-01

    A tumor could be found in any area of the brain and could be of any size, shape, and contrast. There may exist multiple tumors of different types in a human brain at the same time. Accurate tumor area segmentation is considered primary step for treatment of brain tumors. Deep Learning is a set of promising techniques that could provide better results as compared to nondeep learning techniques for segmenting timorous part inside a brain. This article presents a deep convolutional neural network (CNN) to segment brain tumors in MRIs. The proposed network uses BRATS segmentation challenge dataset which is composed of images obtained through four different modalities. Accordingly, we present an extended version of existing network to solve segmentation problem. The network architecture consists of multiple neural network layers connected in sequential order with the feeding of Convolutional feature maps at the peer level. Experimental results on BRATS 2015 benchmark data thus show the usability of the proposed approach and its superiority over the other approaches in this area of research. © 2018 Wiley Periodicals, Inc.

  10. A spatiotemporal atlas of MR intensity, tissue probability and shape of the fetal brain with application to segmentation

    PubMed Central

    Habas, Piotr A.; Kim, Kio; Corbett-Detig, James M.; Rousseau, Francois; Glenn, Orit A.; Barkovich, A. James; Studholme, Colin

    2010-01-01

    Modeling and analysis of MR images of the developing human brain is a challenge due to rapid changes in brain morphology and morphometry. We present an approach to the construction of a spatiotemporal atlas of the fetal brain with temporal models of MR intensity, tissue probability and shape changes. This spatiotemporal model is created from a set of reconstructed MR images of fetal subjects with different gestational ages. Groupwise registration of manual segmentations and voxelwise nonlinear modeling allow us to capture the appearance, disappearance and spatial variation of brain structures over time. Applying this model to atlas-based segmentation, we generate age-specific MR templates and tissue probability maps and use them to initialize automatic tissue delineation in new MR images. The choice of model parameters and the final performance are evaluated using clinical MR scans of young fetuses with gestational ages ranging from 20.57 to 24.71 weeks. Experimental results indicate that quadratic temporal models can correctly capture growth-related changes in the fetal brain anatomy and provide improvement in accuracy of atlas-based tissue segmentation. PMID:20600970

  11. Linking late cognitive outcome with glioma surgery location using resection cavity maps.

    PubMed

    Hendriks, Eef J; Habets, Esther J J; Taphoorn, Martin J B; Douw, Linda; Zwinderman, Aeilko H; Vandertop, W Peter; Barkhof, Frederik; Klein, Martin; De Witt Hamer, Philip C

    2018-05-01

    Patients with a diffuse glioma may experience cognitive decline or improvement upon resective surgery. To examine the impact of glioma location, cognitive alteration after glioma surgery was quantified and related to voxel-based resection probability maps. A total of 59 consecutive patients (range 18-67 years of age) who had resective surgery between 2006 and 2011 for a supratentorial nonenhancing diffuse glioma (grade I-III, WHO 2007) were included in this observational cohort study. Standardized neuropsychological examination and MRI were obtained before and after surgery. Intraoperative stimulation mapping guided resections towards neurological functions (language, sensorimotor function, and visual fields). Maps of resected regions were constructed in standard space. These resection cavity maps were compared between patients with and without new cognitive deficits (z-score difference >1.5 SD between baseline and one year after resection), using a voxel-wise randomization test and calculation of false discovery rates. Brain regions significantly associated with cognitive decline were classified in standard cortical and subcortical anatomy. Cognitive improvement in any domain occurred in 10 (17%) patients, cognitive decline in any domain in 25 (42%), and decline in more than one domain in 10 (17%). The most frequently affected subdomains were attention in 10 (17%) patients and information processing speed in 9 (15%). Resection regions associated with decline in more than one domain were predominantly located in the right hemisphere. For attention decline, no specific region could be identified. For decline in information speed, several regions were found, including the frontal pole and the corpus callosum. Cognitive decline after resective surgery of diffuse glioma is prevalent, in particular, in patients with a tumor located in the right hemisphere without cognitive function mapping. © The Authors Human Brain Mapping Published by Wiley Periodicals, Inc.

  12. Mapping of electrophysiological response to transcranial infrared laser stimulation on the human brain in vivo measured by electroencephalography (Conference Presentation)

    NASA Astrophysics Data System (ADS)

    Wang, Xinlong; Reddy, Divya Dhandapani; Gonzalez-Lima, F.; Liu, Hanli

    2017-02-01

    Transcranial infrared laser stimulation (TILS) is a non-destructive and non-thermal photobiomodulation therapy or process on the human brain; TILS uses infrared light from lasers or LEDs and has gained increased recognition for its beneficial effects on a variety of neurological and psychological conditions. While the mechanism of TILS has been assumed to stem from cytochrome-c-oxidase (CCO), which is the last enzyme in the electron transportation chain and is the primary photoacceptor, no literature is found to report electrophysiological response to TILS. In this study, a 64-channel electroencephalography (EEG) system was employed to monitor electrophysiological activities from 15 healthy human participants before, during and after TILS. A placebo experimental protocol was also applied for rigorous comparison. After recording a 3-minute baseline, we applied a 1064-nm laser with a power of 3.5W on the right forehead of each human participant for 8 minutes, followed by a 5-minute recovery period. In 64-channel EEG data analysis, we utilized several methods (root mean square, principal component analysis followed by independent component analysis, permutation conditional mutual information, and time-frequency wavelet analysis) to reveal differences in electrophysiological response to TILS between the stimulated versus placebo group. The analyzed results were further investigated using general linear model and paired t-test to reveal statistically meaningful responses induced by TILS. Moreover, this study will provide spatial mapping of human electrophysiological and possibly neural network responses to TILS for first time, indicating the potential of EEG to be an effective method for monitoring neurological improvement induced by TILS.

  13. Serum extravasation and cytoskeletal alterations following traumatic brain injury in rats. Comparison of lateral fluid percussion and cortical impact models.

    PubMed

    Hicks, R R; Baldwin, S A; Scheff, S W

    1997-01-01

    Disruption of the blood-brain barrier (BBB) and neuronal cytoskeletal damage were evaluated in two commonly used rat models of traumatic brain injury. Adult rats received a lateral cortical impact (CI) or lateral fluid percussion (FP) injury of mild or moderate severity or a sham procedure. Six hours after trauma, the brains were removed and analyzed with immunocytochemical techniques for alterations in the serum protein, IgG, and the cytoskeletal protein, microtubule-associated protein 2 (MAP2). Both models induced profound alterations in these proteins in the ipsilateral cortex and hippocampus compared to sham-injured controls. Following an injury of moderate severity, the CI injury resulted in greater IgG extravasation in the cortex and hippocampus than the FP injury. Conversely, after a mild injury, IgG extravasation in the hippocampus was greater for FP than CI. All of the animals in the CI group and most of the FP group showed a loss of MAP2 in the hippocampus. The specific subregions within the cortex and hippocampus that were affected by the injury varied between models, despite having identical impact sites. These data demonstrate that there are both similarities and differences between a CI and FP injury on vascular and neuronal cystoskeletal integrity, which should be considered when utilizing these animal models to study selected features of human head injury.

  14. Brain volumetric changes and cognitive ageing during the eighth decade of life

    PubMed Central

    Dickie, David Alexander; Cox, Simon R.; Valdes Hernandez, Maria del C.; Corley, Janie; Royle, Natalie A.; Pattie, Alison; Aribisala, Benjamin S.; Redmond, Paul; Muñoz Maniega, Susana; Taylor, Adele M.; Sibbett, Ruth; Gow, Alan J.; Starr, John M.; Bastin, Mark E.; Wardlaw, Joanna M.; Deary, Ian J.

    2015-01-01

    Abstract Later‐life changes in brain tissue volumes—decreases in the volume of healthy grey and white matter and increases in the volume of white matter hyperintensities (WMH)—are strong candidates to explain some of the variation in ageing‐related cognitive decline. We assessed fluid intelligence, memory, processing speed, and brain volumes (from structural MRI) at mean age 73 years, and at mean age 76 in a narrow‐age sample of older individuals (n = 657 with brain volumetric data at the initial wave, n = 465 at follow‐up). We used latent variable modeling to extract error‐free cognitive levels and slopes. Initial levels of cognitive ability were predictive of subsequent brain tissue volume changes. Initial brain volumes were not predictive of subsequent cognitive changes. Brain volume changes, especially increases in WMH, were associated with declines in each of the cognitive abilities. All statistically significant results were modest in size (absolute r‐values ranged from 0.114 to 0.334). These results build a comprehensive picture of macrostructural brain volume changes and declines in important cognitive faculties during the eighth decade of life. Hum Brain Mapp 36:4910–4925, 2015. © 2015 The Authors. Human Brain Mapping Published by Wiley Periodicals, Inc PMID:26769551

  15. Detection of Normal Aging Effects on Human Brain Metabolite Concentrations and Microstructure with Whole-Brain MR Spectroscopic Imaging and Quantitative MR Imaging.

    PubMed

    Eylers, V V; Maudsley, A A; Bronzlik, P; Dellani, P R; Lanfermann, H; Ding, X-Q

    2016-03-01

    Knowledge of age-related physiological changes in the human brain is a prerequisite to identify neurodegenerative diseases. Therefore, in this study whole-brain (1)H-MRS was used in combination with quantitative MR imaging to study the effects of normal aging on healthy human brain metabolites and microstructure. Sixty healthy volunteers, 21-70 years of age, were studied. Brain maps of the metabolites NAA, creatine and phosphocreatine, and Cho and the tissue irreversible and reversible transverse relaxation times T2 and T2' were derived from the datasets. The relative metabolite concentrations and the values of relaxation times were measured with ROIs placed within the frontal and parietal WM, centrum semiovale, splenium of the corpus callosum, hand motor area, occipital GM, putamen, thalamus, pons ventral/dorsal, and cerebellar white matter and posterior lobe. Linear regression analysis and Pearson correlation tests were used to analyze the data. Aging resulted in decreased NAA concentrations in the occipital GM, putamen, splenium of the corpus callosum, and pons ventral and decreased creatine and phosphocreatine concentrations in the pons dorsal and putamen. Cho concentrations did not change significantly in selected brain regions. T2 increased in the cerebellar white matter and decreased in the splenium of the corpus callosum with aging, while the T2' decreased in the occipital GM, hand motor area, and putamen, and increased in the splenium of the corpus callosum. Correlations were found between NAA concentrations and T2' in the occipital GM and putamen and between creatine and phosphocreatine concentrations and T2' in the putamen. The effects of normal aging on brain metabolites and microstructure are region-dependent. Correlations between both processes are evident in the gray matter. The obtained data could be used as references for future studies on patients. © 2016 by American Journal of Neuroradiology.

  16. The role of symmetry in neural networks and their Laplacian spectra.

    PubMed

    de Lange, Siemon C; van den Heuvel, Martijn P; de Reus, Marcel A

    2016-11-01

    Human and animal nervous systems constitute complexly wired networks that form the infrastructure for neural processing and integration of information. The organization of these neural networks can be analyzed using the so-called Laplacian spectrum, providing a mathematical tool to produce systems-level network fingerprints. In this article, we examine a characteristic central peak in the spectrum of neural networks, including anatomical brain network maps of the mouse, cat and macaque, as well as anatomical and functional network maps of human brain connectivity. We link the occurrence of this central peak to the level of symmetry in neural networks, an intriguing aspect of network organization resulting from network elements that exhibit similar wiring patterns. Specifically, we propose a measure to capture the global level of symmetry of a network and show that, for both empirical networks and network models, the height of the main peak in the Laplacian spectrum is strongly related to node symmetry in the underlying network. Moreover, examination of spectra of duplication-based model networks shows that neural spectra are best approximated using a trade-off between duplication and diversification. Taken together, our results facilitate a better understanding of neural network spectra and the importance of symmetry in neural networks. Copyright © 2016 Elsevier Inc. All rights reserved.

  17. Spatially Regularized Machine Learning for Task and Resting-state fMRI

    PubMed Central

    Song, Xiaomu; Panych, Lawrence P.; Chen, Nan-kuei

    2015-01-01

    Background Reliable mapping of brain function across sessions and/or subjects in task- and resting-state has been a critical challenge for quantitative fMRI studies although it has been intensively addressed in the past decades. New Method A spatially regularized support vector machine (SVM) technique was developed for the reliable brain mapping in task- and resting-state. Unlike most existing SVM-based brain mapping techniques, which implement supervised classifications of specific brain functional states or disorders, the proposed method performs a semi-supervised classification for the general brain function mapping where spatial correlation of fMRI is integrated into the SVM learning. The method can adapt to intra- and inter-subject variations induced by fMRI nonstationarity, and identify a true boundary between active and inactive voxels, or between functionally connected and unconnected voxels in a feature space. Results The method was evaluated using synthetic and experimental data at the individual and group level. Multiple features were evaluated in terms of their contributions to the spatially regularized SVM learning. Reliable mapping results in both task- and resting-state were obtained from individual subjects and at the group level. Comparison with Existing Methods A comparison study was performed with independent component analysis, general linear model, and correlation analysis methods. Experimental results indicate that the proposed method can provide a better or comparable mapping performance at the individual and group level. Conclusions The proposed method can provide accurate and reliable mapping of brain function in task- and resting-state, and is applicable to a variety of quantitative fMRI studies. PMID:26470627

  18. In vivo mapping of current density distribution in brain tissues during deep brain stimulation (DBS)

    NASA Astrophysics Data System (ADS)

    Sajib, Saurav Z. K.; Oh, Tong In; Kim, Hyung Joong; Kwon, Oh In; Woo, Eung Je

    2017-01-01

    New methods for in vivo mapping of brain responses during deep brain stimulation (DBS) are indispensable to secure clinical applications. Assessment of current density distribution, induced by internally injected currents, may provide an alternative method for understanding the therapeutic effects of electrical stimulation. The current flow and pathway are affected by internal conductivity, and can be imaged using magnetic resonance-based conductivity imaging methods. Magnetic resonance electrical impedance tomography (MREIT) is an imaging method that can enable highly resolved mapping of electromagnetic tissue properties such as current density and conductivity of living tissues. In the current study, we experimentally imaged current density distribution of in vivo canine brains by applying MREIT to electrical stimulation. The current density maps of three canine brains were calculated from the measured magnetic flux density data. The absolute current density values of brain tissues, including gray matter, white matter, and cerebrospinal fluid were compared to assess the active regions during DBS. The resulting current density in different tissue types may provide useful information about current pathways and volume activation for adjusting surgical planning and understanding the therapeutic effects of DBS.

  19. The Effects of Low-Dose Bisphenol A and Bisphenol F on Neural Differentiation of a Fetal Brain-Derived Neural Progenitor Cell Line.

    PubMed

    Fujiwara, Yuki; Miyazaki, Wataru; Koibuchi, Noriyuki; Katoh, Takahiko

    2018-01-01

    Environmental chemicals are known to disrupt the endocrine system in humans and to have adverse effects on several organs including the developing brain. Recent studies indicate that exposure to environmental chemicals during gestation can interfere with neuronal differentiation, subsequently affecting normal brain development in newborns. Xenoestrogen, bisphenol A (BPA), which is widely used in plastic products, is one such chemical. Adverse effects of exposure to BPA during pre- and postnatal periods include the disruption of brain function. However, the effect of BPA on neural differentiation remains unclear. In this study, we explored the effects of BPA or bisphenol F (BPF), an alternative compound for BPA, on neural differentiation using ReNcell, a human fetus-derived neural progenitor cell line. Maintenance in growth factor-free medium initiated the differentiation of ReNcell to neuronal cells including neurons, astrocytes, and oligodendrocytes. We exposed the cells to BPA or BPF for 3 days from the period of initiation and performed real-time PCR for neural markers such as β III-tubulin and glial fibrillary acidic protein (GFAP), and Olig2. The β III-tubulin mRNA level decreased in response to BPA, but not BPF, exposure. We also observed that the number of β III-tubulin-positive cells in the BPA-exposed group was less than that of the control group. On the other hand, there were no changes in the MAP2 mRNA level. These results indicate that BPA disrupts neural differentiation in human-derived neural progenitor cells, potentially disrupting brain development.

  20. The Myth of the Normal, Average Human Brain—The ICBM Experience: (1) Subject Screening and Eligibility

    PubMed Central

    Mazziotta, John C.; Woods, Roger; Iacoboni, Marco; Sicotte, Nancy; Yaden, Kami; Tran, Mary; Bean, Courtney; Kaplan, Jonas; Toga, Arthur W.

    2009-01-01

    In the course of developing an atlas and reference system for the normal human brain throughout the human age span from structural and functional brain imaging data, the International Consortium for Brain Mapping (ICBM) developed a set of “normal” criteria for subject inclusion and the associated exclusion criteria. The approach was to minimize inclusion of subjects with any medical disorders that could affect brain structure or function. In the past two years, a group of 1,685 potential subjects responded to solicitation advertisements at one of the consortium sites (UCLA). Subjects were screened by a detailed telephone interview and then had an in-person history and physical examination. Of those who responded to the advertisement and considered themselves to be normal, only 31.6% (532 subjects) passed the telephone screening process. Of the 348 individuals who submitted to in-person history and physical examinations, only 51.7% passed these screening procedures. Thus, only 10.7% of those individuals who responded to the original advertisement qualified for imaging. The most frequent cause for exclusion in the second phase of subject screening was high blood pressure followed by abnormal signs on neurological examination. It is concluded that the majority of individuals who consider themselves normal by self-report are found not to be so by detailed historical interviews about underlying medical conditions and by thorough medical and neurological examinations. Recommendations are made with regard to the inclusion of subjects in brain imaging studies and the criteria used to select them. PMID:18775497

  1. Separating pitch chroma and pitch height in the human brain

    PubMed Central

    Warren, J. D.; Uppenkamp, S.; Patterson, R. D.; Griffiths, T. D.

    2003-01-01

    Musicians recognize pitch as having two dimensions. On the keyboard, these are illustrated by the octave and the cycle of notes within the octave. In perception, these dimensions are referred to as pitch height and pitch chroma, respectively. Pitch chroma provides a basis for presenting acoustic patterns (melodies) that do not depend on the particular sound source. In contrast, pitch height provides a basis for segregation of notes into streams to separate sound sources. This paper reports a functional magnetic resonance experiment designed to search for distinct mappings of these two types of pitch change in the human brain. The results show that chroma change is specifically represented anterior to primary auditory cortex, whereas height change is specifically represented posterior to primary auditory cortex. We propose that tracking of acoustic information streams occurs in anterior auditory areas, whereas the segregation of sound objects (a crucial aspect of auditory scene analysis) depends on posterior areas. PMID:12909719

  2. Separating pitch chroma and pitch height in the human brain.

    PubMed

    Warren, J D; Uppenkamp, S; Patterson, R D; Griffiths, T D

    2003-08-19

    Musicians recognize pitch as having two dimensions. On the keyboard, these are illustrated by the octave and the cycle of notes within the octave. In perception, these dimensions are referred to as pitch height and pitch chroma, respectively. Pitch chroma provides a basis for presenting acoustic patterns (melodies) that do not depend on the particular sound source. In contrast, pitch height provides a basis for segregation of notes into streams to separate sound sources. This paper reports a functional magnetic resonance experiment designed to search for distinct mappings of these two types of pitch change in the human brain. The results show that chroma change is specifically represented anterior to primary auditory cortex, whereas height change is specifically represented posterior to primary auditory cortex. We propose that tracking of acoustic information streams occurs in anterior auditory areas, whereas the segregation of sound objects (a crucial aspect of auditory scene analysis) depends on posterior areas.

  3. Differences in Information Mapping Strategies in Left and Right Brain Learners.

    ERIC Educational Resources Information Center

    Hauck, LaVerne S., Jr.

    The Information Mapping technique was used to present a learning packet, and its usefulness in helping right-brain cerebrally dominant students to achieve the same level of subject mastery as their left-brain counterparts was examined. Reading level, grade point average, and gender were also analyzed. Torrance's "Your Style of Learning and…

  4. From gene networks to drugs: systems pharmacology approaches for AUD.

    PubMed

    Ferguson, Laura B; Harris, R Adron; Mayfield, Roy Dayne

    2018-06-01

    The alcohol research field has amassed an impressive number of gene expression datasets spanning key brain areas for addiction, species (humans as well as multiple animal models), and stages in the addiction cycle (binge/intoxication, withdrawal/negative effect, and preoccupation/anticipation). These data have improved our understanding of the molecular adaptations that eventually lead to dysregulation of brain function and the chronic, relapsing disorder of addiction. Identification of new medications to treat alcohol use disorder (AUD) will likely benefit from the integration of genetic, genomic, and behavioral information included in these important datasets. Systems pharmacology considers drug effects as the outcome of the complex network of interactions a drug has rather than a single drug-molecule interaction. Computational strategies based on this principle that integrate gene expression signatures of pharmaceuticals and disease states have shown promise for identifying treatments that ameliorate disease symptoms (called in silico gene mapping or connectivity mapping). In this review, we suggest that gene expression profiling for in silico mapping is critical to improve drug repurposing and discovery for AUD and other psychiatric illnesses. We highlight studies that successfully apply gene mapping computational approaches to identify or repurpose pharmaceutical treatments for psychiatric illnesses. Furthermore, we address important challenges that must be overcome to maximize the potential of these strategies to translate to the clinic and improve healthcare outcomes.

  5. Network localization of neurological symptoms from focal brain lesions

    PubMed Central

    Prasad, Sashank; Liu, Hesheng; Liu, Qi; Pascual-Leone, Alvaro; Caviness, Verne S.; Fox, Michael D.

    2015-01-01

    A traditional and widely used approach for linking neurological symptoms to specific brain regions involves identifying overlap in lesion location across patients with similar symptoms, termed lesion mapping. This approach is powerful and broadly applicable, but has limitations when symptoms do not localize to a single region or stem from dysfunction in regions connected to the lesion site rather than the site itself. A newer approach sensitive to such network effects involves functional neuroimaging of patients, but this requires specialized brain scans beyond routine clinical data, making it less versatile and difficult to apply when symptoms are rare or transient. In this article we show that the traditional approach to lesion mapping can be expanded to incorporate network effects into symptom localization without the need for specialized neuroimaging of patients. Our approach involves three steps: (i) transferring the three-dimensional volume of a brain lesion onto a reference brain; (ii) assessing the intrinsic functional connectivity of the lesion volume with the rest of the brain using normative connectome data; and (iii) overlapping lesion-associated networks to identify regions common to a clinical syndrome. We first tested our approach in peduncular hallucinosis, a syndrome of visual hallucinations following subcortical lesions long hypothesized to be due to network effects on extrastriate visual cortex. While the lesions themselves were heterogeneously distributed with little overlap in lesion location, 22 of 23 lesions were negatively correlated with extrastriate visual cortex. This network overlap was specific compared to other subcortical lesions (P < 10−5) and relative to other cortical regions (P < 0.01). Next, we tested for generalizability of our technique by applying it to three additional lesion syndromes: central post-stroke pain, auditory hallucinosis, and subcortical aphasia. In each syndrome, heterogeneous lesions that themselves had little overlap showed significant network overlap in cortical areas previously implicated in symptom expression (P < 10−4). These results suggest that (i) heterogeneous lesions producing similar symptoms share functional connectivity to specific brain regions involved in symptom expression; and (ii) publically available human connectome data can be used to incorporate these network effects into traditional lesion mapping approaches. Because the current technique requires no specialized imaging of patients it may prove a versatile and broadly applicable approach for localizing neurological symptoms in the setting of brain lesions. PMID:26264514

  6. Advanced MR Imaging of the Human Nucleus Accumbens--Additional Guiding Tool for Deep Brain Stimulation.

    PubMed

    Lucas-Neto, Lia; Reimão, Sofia; Oliveira, Edson; Rainha-Campos, Alexandre; Sousa, João; Nunes, Rita G; Gonçalves-Ferreira, António; Campos, Jorge G

    2015-07-01

    The human nucleus accumbens (Acc) has become a target for deep brain stimulation (DBS) in some neuropsychiatric disorders. Nonetheless, even with the most recent advances in neuroimaging it remains difficult to accurately delineate the Acc and closely related subcortical structures, by conventional MRI sequences. It is our purpose to perform a MRI study of the human Acc and to determine whether there are reliable anatomical landmarks that enable the precise location and identification of the nucleus and its core/shell division. For the Acc identification and delineation, based on anatomical landmarks, T1WI, T1IR and STIR 3T-MR images were acquired in 10 healthy volunteers. Additionally, 32-direction DTI was obtained for Acc segmentation. Seed masks for the Acc were generated with FreeSurfer and probabilistic tractography was performed using FSL. The probability of connectivity between the seed voxels and distinct brain areas was determined and subjected to k-means clustering analysis, defining 2 different regions. With conventional T1WI, the Acc borders are better defined through its surrounding anatomical structures. The DTI color-coded vector maps and IR sequences add further detail in the Acc identification and delineation. Additionally, using probabilistic tractography it is possible to segment the Acc into a core and shell division and establish its structural connectivity with different brain areas. Advanced MRI techniques allow in vivo delineation and segmentation of the human Acc and represent an additional guiding tool in the precise and safe target definition for DBS. © 2015 International Neuromodulation Society.

  7. An Intracranial Electroencephalography (iEEG) Brain Function Mapping Tool with an Application to Epilepsy Surgery Evaluation.

    PubMed

    Wang, Yinghua; Yan, Jiaqing; Wen, Jianbin; Yu, Tao; Li, Xiaoli

    2016-01-01

    Before epilepsy surgeries, intracranial electroencephalography (iEEG) is often employed in function mapping and epileptogenic foci localization. Although the implanted electrodes provide crucial information for epileptogenic zone resection, a convenient clinical tool for electrode position registration and Brain Function Mapping (BFM) visualization is still lacking. In this study, we developed a BFM Tool, which facilitates electrode position registration and BFM visualization, with an application to epilepsy surgeries. The BFM Tool mainly utilizes electrode location registration and function mapping based on pre-defined brain models from other software. In addition, the electrode node and mapping properties, such as the node size/color, edge color/thickness, mapping method, can be adjusted easily using the setting panel. Moreover, users may manually import/export location and connectivity data to generate figures for further application. The role of this software is demonstrated by a clinical study of language area localization. The BFM Tool helps clinical doctors and researchers visualize implanted electrodes and brain functions in an easy, quick and flexible manner. Our tool provides convenient electrode registration, easy brain function visualization, and has good performance. It is clinical-oriented and is easy to deploy and use. The BFM tool is suitable for epilepsy and other clinical iEEG applications.

  8. An Intracranial Electroencephalography (iEEG) Brain Function Mapping Tool with an Application to Epilepsy Surgery Evaluation

    PubMed Central

    Wang, Yinghua; Yan, Jiaqing; Wen, Jianbin; Yu, Tao; Li, Xiaoli

    2016-01-01

    Objects: Before epilepsy surgeries, intracranial electroencephalography (iEEG) is often employed in function mapping and epileptogenic foci localization. Although the implanted electrodes provide crucial information for epileptogenic zone resection, a convenient clinical tool for electrode position registration and Brain Function Mapping (BFM) visualization is still lacking. In this study, we developed a BFM Tool, which facilitates electrode position registration and BFM visualization, with an application to epilepsy surgeries. Methods: The BFM Tool mainly utilizes electrode location registration and function mapping based on pre-defined brain models from other software. In addition, the electrode node and mapping properties, such as the node size/color, edge color/thickness, mapping method, can be adjusted easily using the setting panel. Moreover, users may manually import/export location and connectivity data to generate figures for further application. The role of this software is demonstrated by a clinical study of language area localization. Results: The BFM Tool helps clinical doctors and researchers visualize implanted electrodes and brain functions in an easy, quick and flexible manner. Conclusions: Our tool provides convenient electrode registration, easy brain function visualization, and has good performance. It is clinical-oriented and is easy to deploy and use. The BFM tool is suitable for epilepsy and other clinical iEEG applications. PMID:27199729

  9. Direct cortical hemodynamic mapping of somatotopy of pig nostril sensation by functional near-infrared cortical imaging (fNCI).

    PubMed

    Uga, Minako; Saito, Toshiyuki; Sano, Toshifumi; Yokota, Hidenori; Oguro, Keiji; Rizki, Edmi Edison; Mizutani, Tsutomu; Katura, Takusige; Dan, Ippeita; Watanabe, Eiju

    2014-05-01

    Functional near-infrared spectroscopy (fNIRS) is a neuroimaging technique for the noninvasive monitoring of human brain activation states utilizing the coupling between neural activity and regional cerebral hemodynamics. Illuminators and detectors, together constituting optodes, are placed on the scalp, but due to the presence of head tissues, an inter-optode distance of more than 2.5cm is necessary to detect cortical signals. Although direct cortical monitoring with fNIRS has been pursued, a high-resolution visualization of hemodynamic changes associated with sensory, motor and cognitive neural responses directly from the cortical surface has yet to be realized. To acquire robust information on the hemodynamics of the cortex, devoid of signal complications in transcranial measurement, we devised a functional near-infrared cortical imaging (fNCI) technique. Here we demonstrate the first direct functional measurement of temporal and spatial patterns of cortical hemodynamics using the fNCI technique. For fNCI, inter-optode distance was set at 5mm, and light leakage from illuminators was prevented by a special optode holder made of a light-shielding rubber sheet. fNCI successfully detected the somatotopy of pig nostril sensation, as assessed in comparison with concurrent and sequential somatosensory-evoked potential (SEP) measurements on the same stimulation sites. Accordingly, the fNCI system realized a direct cortical hemodynamic measurement with a spatial resolution comparable to that of SEP mapping on the rostral region of the pig brain. This study provides an important initial step toward realizing functional cortical hemodynamic monitoring during neurosurgery of human brains. Copyright © 2014. Published by Elsevier Inc.

  10. A Model of the Superior Colliculus Predicts Fixation Locations during Scene Viewing and Visual Search.

    PubMed

    Adeli, Hossein; Vitu, Françoise; Zelinsky, Gregory J

    2017-02-08

    Modern computational models of attention predict fixations using saliency maps and target maps, which prioritize locations for fixation based on feature contrast and target goals, respectively. But whereas many such models are biologically plausible, none have looked to the oculomotor system for design constraints or parameter specification. Conversely, although most models of saccade programming are tightly coupled to underlying neurophysiology, none have been tested using real-world stimuli and tasks. We combined the strengths of these two approaches in MASC, a model of attention in the superior colliculus (SC) that captures known neurophysiological constraints on saccade programming. We show that MASC predicted the fixation locations of humans freely viewing naturalistic scenes and performing exemplar and categorical search tasks, a breadth achieved by no other existing model. Moreover, it did this as well or better than its more specialized state-of-the-art competitors. MASC's predictive success stems from its inclusion of high-level but core principles of SC organization: an over-representation of foveal information, size-invariant population codes, cascaded population averaging over distorted visual and motor maps, and competition between motor point images for saccade programming, all of which cause further modulation of priority (attention) after projection of saliency and target maps to the SC. Only by incorporating these organizing brain principles into our models can we fully understand the transformation of complex visual information into the saccade programs underlying movements of overt attention. With MASC, a theoretical footing now exists to generate and test computationally explicit predictions of behavioral and neural responses in visually complex real-world contexts. SIGNIFICANCE STATEMENT The superior colliculus (SC) performs a visual-to-motor transformation vital to overt attention, but existing SC models cannot predict saccades to visually complex real-world stimuli. We introduce a brain-inspired SC model that outperforms state-of-the-art image-based competitors in predicting the sequences of fixations made by humans performing a range of everyday tasks (scene viewing and exemplar and categorical search), making clear the value of looking to the brain for model design. This work is significant in that it will drive new research by making computationally explicit predictions of SC neural population activity in response to naturalistic stimuli and tasks. It will also serve as a blueprint for the construction of other brain-inspired models, helping to usher in the next generation of truly intelligent autonomous systems. Copyright © 2017 the authors 0270-6474/17/371453-15$15.00/0.

  11. Up-regulation of microtubule-associated protein 2 accompanying the filial imprinting of domestic chicks (Gallus gallus domesticus).

    PubMed

    Yamaguchi, Shinji; Fujii-Taira, Ikuko; Murakami, Akio; Hirose, Naoki; Aoki, Naoya; Izawa, Ei-Ichi; Fujimoto, Yasuyuki; Takano, Tatsuya; Matsushima, Toshiya; Homma, Koichi J

    2008-06-15

    Using cDNA microarrays, we have identified elsewhere the genes of microtubule-associated proteins as a group up-regulated in newly hatched chick brains after filial imprinting training. Here we show by in situ hybridization that the mRNA for the microtubule-associated protein 2 (MAP2) gene was enriched in the mesopallium and the hippocampus in the trained chick brain. The regionally specific enrichments of MAP2 mRNA were not observed in the brain of dark-reared or light-exposed chick as controls, implying an association between the degree of expression and the strength of the learned preference. In agreement with the gene expression, MAP2 protein was accumulated in the mesopallium of the trained chick brain, but not in the brains of the controls. The accumulation of MAP2 was found in the cytosol of neurons and co-localized with beta-tubulin, suggesting a change in microtubule assembly. Our results suggest a postnatal reorganization of cytoskeleton following filial imprinting.

  12. High-resolution maps of real and illusory tactile activation in primary somatosensory cortex in individual monkeys with functional magnetic resonance imaging and optical imaging.

    PubMed

    Chen, Li M; Turner, Gregory H; Friedman, Robert M; Zhang, Na; Gore, John C; Roe, Anna W; Avison, Malcolm J

    2007-08-22

    Although blood oxygenation level-dependent (BOLD) functional magnetic resonance imaging (fMRI) has been widely used to explore human brain function, questions remain regarding the ultimate spatial resolution of positive BOLD fMRI, and indeed the extent to which functional maps revealed by positive BOLD correlate spatially with maps obtained with other high-spatial-resolution mapping techniques commonly used in animals, such as optical imaging of intrinsic signal (OIS) and single-unit electrophysiology. Here, we demonstrate that the positive BOLD signal at 9.4T can reveal the fine topography of individual fingerpads in single-condition activation maps in nonhuman primates. These digit maps are similar to maps obtained from the same animal using intrinsic optical imaging. Furthermore, BOLD fMRI reliably resolved submillimeter spatial shifts in activation in area 3b previously identified with OIS (Chen et al., 2003) as neural correlates of the "funneling illusion." These data demonstrate that at high field, high-spatial-resolution topographic maps can be achieved using the positive BOLD signal, weakening previous notions regarding the spatial specificity of the positive BOLD signal.

  13. Apparent diffusion coefficient mapping in medulloblastoma predicts non-infiltrative surgical planes.

    PubMed

    Marupudi, Neena I; Altinok, Deniz; Goncalves, Luis; Ham, Steven D; Sood, Sandeep

    2016-11-01

    An appropriate surgical approach for posterior fossa lesions is to start tumor removal from areas with a defined plane to where tumor is infiltrating the brainstem or peduncles. This surgical approach minimizes risk of damage to eloquent areas. Although magnetic resonance imaging (MRI) is the current standard preoperative imaging obtained for diagnosis and surgical planning of pediatric posterior fossa tumors, it offers limited information on the infiltrative planes between tumor and normal structures in patients with medulloblastomas. Because medulloblastomas demonstrate diffusion restriction on apparent diffusion coefficient map (ADC map) sequences, we investigated the role of ADC map in predicting infiltrative and non-infiltrative planes along the brain stem and/or cerebellar peduncles by medulloblastomas prior to surgery. Thirty-four pediatric patients with pathologically confirmed medulloblastomas underwent surgical resection at our facility from 2004 to 2012. An experienced pediatric neuroradiologist reviewed the brain MRIs/ADC map, assessing the planes between the tumor and cerebellar peduncles/brain stem. An independent evaluator documented surgical findings from operative reports for comparison to the radiographic findings. The radiographic findings were statistically compared to the documented intraoperative findings to determine predictive value of the test in identifying tumor infiltration of the brain stem cerebellar peduncles. Twenty-six patients had preoperative ADC mapping completed and thereby, met inclusion criteria. Mean age at time of surgery was 8.3 ± 4.6 years. Positive predictive value of ADC maps to predict tumor invasion of the brain stem and cerebellar peduncles ranged from 69 to 88 %; negative predictive values ranged from 70 to 89 %. Sensitivity approached 93 % while specificity approached 78 %. ADC maps are valuable in predicting the infiltrative and non-infiltrative planes along the tumor and brain stem interface in medulloblastomas. Inclusion and evaluation of ADC maps in preoperative evaluation can assist in surgical resection planning in patients with medulloblastoma.

  14. Architecture of fluid intelligence and working memory revealed by lesion mapping.

    PubMed

    Barbey, Aron K; Colom, Roberto; Paul, Erick J; Grafman, Jordan

    2014-03-01

    Although cognitive neuroscience has made valuable progress in understanding the role of the prefrontal cortex in human intelligence, the functional networks that support adaptive behavior and novel problem solving remain to be well characterized. Here, we studied 158 human brain lesion patients to investigate the cognitive and neural foundations of key competencies for fluid intelligence and working memory. We administered a battery of neuropsychological tests, including the Wechsler Adult Intelligence Scale (WAIS) and the N-Back task. Latent variable modeling was applied to obtain error-free scores of fluid intelligence and working memory, followed by voxel-based lesion-symptom mapping to elucidate their neural substrates. The observed latent variable modeling and lesion results support an integrative framework for understanding the architecture of fluid intelligence and working memory and make specific recommendations for the interpretation and application of the WAIS and N-Back task to the study of fluid intelligence in health and disease.

  15. 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.

  16. The Road to FUNCTIONAL IMAGING and ULTRAHIGH FIELDS

    PubMed Central

    Uğurbil, Kâmil

    2012-01-01

    The Center for Magnetic Resonance (CMRR) at the University of Minnesota was one of laboratories where the work that simultaneously and independently introduced functional magnetic resonance imaging (fMRI) of human brain activity was carried out. However, unlike other laboratories pursuing fMRI at the time, our work was performed at 4 Tesla magnetic field and coincided with the effort to push human magnetic resonance imaging to field strength significantly beyond 1.5 Tesla which was the high-end standard of the time. The human fMRI experiments performed in CMRR were planned between two colleagues who had known each other and had worked together previously in Bell Laboratories, namely Seiji Ogawa and myself, immediately after the Blood Oxygenation Level Dependent (BOLD) contrast was developed by Seiji. We were waiting for our first human system, a 4 Tesla system, to arrive in order to attempt at imaging brain activity in the human brain and these were the first experiments we performed on the 4 Tesla instrument in CMRR when it became marginally operational. This was a prelude to a subsequent systematic push we initiated for exploiting higher magnetic fields to improve the accuracy and sensitivity of fMRI maps, first going to 9.4 Tesla for animal model studies and subsequently developing a 7 Tesla human system for the first time. Steady improvements in high field instrumentation and ever expanding armamentarium of image acquisition and engineering solutions to challenges posed by ultrahigh fields has brought fMRI to submillimeter resolution in the whole brain at 7 Tesla, the scale necessary to reach cortical columns and laminar differentiation in the whole brain. The solutions that emerged in response to technological challenges posed by 7 Tesla also propagated and continues to propagate to lower field clinical systems, a major advantage of the ultrahigh fields effort that is underappreciated. Further improvements at 7T are inevitable. Further translation of these improvements to lower field clinical systems to achieve new capabilities and to magnetic fields significantly higher than 7 Tesla to enable human imaging is inescapable. PMID:22333670

  17. Brain Mapping of drug addiction in witdrawal condition based P300 Signals

    NASA Astrophysics Data System (ADS)

    Turnip, Arjon; Esti Kusumandari, Dwi; Hidayat, Teddy

    2018-04-01

    Drug abuse for a long time will slowly cause changes in brain structure and performance. These changes tend to occur in the front of the brain which is directly interfere the concentration and the decision-making process. In this study an experiment involving 10 drug users was performed. The process of recording data with EEG system is conducted during craving condition and 1 hour after taking methadone. From brain mapping results obtained that brain activity tend to occur in the upper layer of the brain during craving conditions and tend to be in the midle layer of the brain after one hour of taking methadone.

  18. Adaptation of tick-borne encephalitis virus from human brain to different cell cultures induces multiple genomic substitutions.

    PubMed

    Ponomareva, Eugenia P; Ternovoi, Vladimir A; Mikryukova, Tamara P; Protopopova, Elena V; Gladysheva, Anastasia V; Shvalov, Alexander N; Konovalova, Svetlana N; Chausov, Eugene V; Loktev, Valery B

    2017-10-01

    The C11-13 strain from the Siberian subtype of tick-borne encephalitis virus (TBEV) was isolated from human brain using pig embryo kidney (PEK), 293, and Neuro-2a cells. Analysis of the complete viral genome of the C11-13 variants during six passages in these cells revealed that the cell-adapted C11-13 variants had multiple amino acid substitutions as compared to TBEV from human brain. Seven out of eight amino acids substitutions in the high-replicating C11-13(PEK) variant mapped to non-structural proteins; 13 out of 14 substitutions in the well-replicating C11-13(293) variant, and all four substitutions in the low-replicating C11-13(Neuro-2a) variant were also localized in non-structural proteins, predominantly in the NS2a (2), NS3 (6) and NS5 (3) proteins. The substitutions NS2a 1067 (Asn → Asp), NS2a 1168 (Leu → Val) in the N-terminus of NS2a and NS3 1745 (His → Gln) in the helicase domain of NS3 were found in all selected variants. We postulate that multiple substitutions in the NS2a, NS3 and NS5 genes play a key role in adaptation of TBEV to different cells.

  19. In vivo functional connectome of human brainstem nuclei of the ascending arousal, autonomic, and motor systems by high spatial resolution 7-Tesla fMRI.

    PubMed

    Bianciardi, Marta; Toschi, Nicola; Eichner, Cornelius; Polimeni, Jonathan R; Setsompop, Kawin; Brown, Emery N; Hämäläinen, Matti S; Rosen, Bruce R; Wald, Lawrence L

    2016-06-01

    Our aim was to map the in vivo human functional connectivity of several brainstem nuclei with the rest of the brain by using seed-based correlation of ultra-high magnetic field functional magnetic resonance imaging (fMRI) data. We used the recently developed template of 11 brainstem nuclei derived from multi-contrast structural MRI at 7 Tesla as seed regions to determine their connectivity to the rest of the brain. To achieve this, we used the increased contrast-to-noise ratio of 7-Tesla fMRI compared with 3 Tesla and time-efficient simultaneous multi-slice imaging to cover the brain with high spatial resolution (1.1-mm isotropic nominal resolution) while maintaining a short repetition time (2.5 s). The delineated Pearson's correlation-based functional connectivity diagrams (connectomes) of 11 brainstem nuclei of the ascending arousal, motor, and autonomic systems from 12 controls are presented and discussed in the context of existing histology and animal work. Considering that the investigated brainstem nuclei play a crucial role in several vital functions, the delineated preliminary connectomes might prove useful for future in vivo research and clinical studies of human brainstem function and pathology, including disorders of consciousness, sleep disorders, autonomic disorders, Parkinson's disease, and other motor disorders.

  20. No-carrier-added [.sup.18 F]-N-fluoroalkylspiroperidols

    DOEpatents

    Shiue, Chyng-Yann; Wolf, Alfred P.; Bai, Lan-Qin; Teng, Ren-Tui

    1989-01-01

    There is disclosed radioligands labeled with the position emitting radionuclide [.sup.18 F] suitable for dynamic study in living humans with position emission transaxial tomography. These new [.sup.18 F]-N-fluoroalkylspiroperidols, wherein the alkyl group contains from 2-6 carbon atoms, exhibit extremely high affinity for the dopamine receptors and provide enhanced uptake and retention in the brain concomitant with reduced radiation burden. These characteristics all combine to make these new radioligands useful for mapping dopamine receptors in normal and disease states in the living brain. Additionally, a new synthetic procedure for these radioligands as well as a new procedure for preparing the radiolabeled alkyl halide alkylating reagents are also disclosed.

  1. Seventh Graders' Academic Achievement, Creativity, and Ability to Construct a Cross-Domain Concept Map--A Brain Function Perspective

    ERIC Educational Resources Information Center

    Yeh, Yu-Chu

    2004-01-01

    This study proposes an interactive model of "cross-domain" concept mapping with an emphasis on brain functions, and it further investigates the relationships between academic achievement, creative thinking, and cross-domain concept mapping. Sixty-nine seventh graders participated in this study which employed two 50-minute instructional…

  2. Heterogeneous fractionation profiles of meta-analytic coactivation networks.

    PubMed

    Laird, Angela R; Riedel, Michael C; Okoe, Mershack; Jianu, Radu; Ray, Kimberly L; Eickhoff, Simon B; Smith, Stephen M; Fox, Peter T; Sutherland, Matthew T

    2017-04-01

    Computational cognitive neuroimaging approaches can be leveraged to characterize the hierarchical organization of distributed, functionally specialized networks in the human brain. To this end, we performed large-scale mining across the BrainMap database of coordinate-based activation locations from over 10,000 task-based experiments. Meta-analytic coactivation networks were identified by jointly applying independent component analysis (ICA) and meta-analytic connectivity modeling (MACM) across a wide range of model orders (i.e., d=20-300). We then iteratively computed pairwise correlation coefficients for consecutive model orders to compare spatial network topologies, ultimately yielding fractionation profiles delineating how "parent" functional brain systems decompose into constituent "child" sub-networks. Fractionation profiles differed dramatically across canonical networks: some exhibited complex and extensive fractionation into a large number of sub-networks across the full range of model orders, whereas others exhibited little to no decomposition as model order increased. Hierarchical clustering was applied to evaluate this heterogeneity, yielding three distinct groups of network fractionation profiles: high, moderate, and low fractionation. BrainMap-based functional decoding of resultant coactivation networks revealed a multi-domain association regardless of fractionation complexity. Rather than emphasize a cognitive-motor-perceptual gradient, these outcomes suggest the importance of inter-lobar connectivity in functional brain organization. We conclude that high fractionation networks are complex and comprised of many constituent sub-networks reflecting long-range, inter-lobar connectivity, particularly in fronto-parietal regions. In contrast, low fractionation networks may reflect persistent and stable networks that are more internally coherent and exhibit reduced inter-lobar communication. Copyright © 2017 Elsevier Inc. All rights reserved.

  3. Heterogeneous fractionation profiles of meta-analytic coactivation networks

    PubMed Central

    Laird, Angela R.; Riedel, Michael C.; Okoe, Mershack; Jianu, Radu; Ray, Kimberly L.; Eickhoff, Simon B.; Smith, Stephen M.; Fox, Peter T.; Sutherland, Matthew T.

    2017-01-01

    Computational cognitive neuroimaging approaches can be leveraged to characterize the hierarchical organization of distributed, functionally specialized networks in the human brain. To this end, we performed large-scale mining across the BrainMap database of coordinate-based activation locations from over 10,000 task-based experiments. Meta-analytic coactivation networks were identified by jointly applying independent component analysis (ICA) and meta-analytic connectivity modeling (MACM) across a wide range of model orders (i.e., d = 20 to 300). We then iteratively computed pairwise correlation coefficients for consecutive model orders to compare spatial network topologies, ultimately yielding fractionation profiles delineating how “parent” functional brain systems decompose into constituent “child” sub-networks. Fractionation profiles differed dramatically across canonical networks: some exhibited complex and extensive fractionation into a large number of sub-networks across the full range of model orders, whereas others exhibited little to no decomposition as model order increased. Hierarchical clustering was applied to evaluate this heterogeneity, yielding three distinct groups of network fractionation profiles: high, moderate, and low fractionation. BrainMap-based functional decoding of resultant coactivation networks revealed a multi-domain association regardless of fractionation complexity. Rather than emphasize a cognitive-motor-perceptual gradient, these outcomes suggest the importance of inter-lobar connectivity in functional brain organization. We conclude that high fractionation networks are complex and comprised of many constituent sub-networks reflecting long-range, inter-lobar connectivity, particularly in fronto-parietal regions. In contrast, low fractionation networks may reflect persistent and stable networks that are more internally coherent and exhibit reduced inter-lobar communication. PMID:28222386

  4. Planar implantable sensor for in vivo measurement of cellular oxygen metabolism in brain tissue.

    PubMed

    Tsytsarev, Vassiliy; Akkentli, Fatih; Pumbo, Elena; Tang, Qinggong; Chen, Yu; Erzurumlu, Reha S; Papkovsky, Dmitri B

    2017-04-01

    Brain imaging methods are continually improving. Imaging of the cerebral cortex is widely used in both animal experiments and charting human brain function in health and disease. Among the animal models, the rodent cerebral cortex has been widely used because of patterned neural representation of the whiskers on the snout and relative ease of activating cortical tissue with whisker stimulation. We tested a new planar solid-state oxygen sensor comprising a polymeric film with a phosphorescent oxygen-sensitive coating on the working side, to monitor dynamics of oxygen metabolism in the cerebral cortex following sensory stimulation. Sensory stimulation led to changes in oxygenation and deoxygenation processes of activated areas in the barrel cortex. We demonstrate the possibility of dynamic mapping of relative changes in oxygenation in live mouse brain tissue with such a sensor. Oxygenation-based functional magnetic resonance imaging (fMRI) is very effective method for functional brain mapping but have high costs and limited spatial resolution. Optical imaging of intrinsic signal (IOS) does not provide the required sensitivity, and voltage-sensitive dye optical imaging (VSDi) has limited applicability due to significant toxicity of the voltage-sensitive dye. Our planar solid-state oxygen sensor imaging approach circumvents these limitations, providing a simple optical contrast agent with low toxicity and rapid application. The planar solid-state oxygen sensor described here can be used as a tool in visualization and real-time analysis of sensory-evoked neural activity in vivo. Further, this approach allows visualization of local neural activity with high temporal and spatial resolution. Copyright © 2017 Elsevier B.V. All rights reserved.

  5. Simultaneous Control of Error Rates in fMRI Data Analysis

    PubMed Central

    Kang, Hakmook; Blume, Jeffrey; Ombao, Hernando; Badre, David

    2015-01-01

    The key idea of statistical hypothesis testing is to fix, and thereby control, the Type I error (false positive) rate across samples of any size. Multiple comparisons inflate the global (family-wise) Type I error rate and the traditional solution to maintaining control of the error rate is to increase the local (comparison-wise) Type II error (false negative) rates. However, in the analysis of human brain imaging data, the number of comparisons is so large that this solution breaks down: the local Type II error rate ends up being so large that scientifically meaningful analysis is precluded. Here we propose a novel solution to this problem: allow the Type I error rate to converge to zero along with the Type II error rate. It works because when the Type I error rate per comparison is very small, the accumulation (or global) Type I error rate is also small. This solution is achieved by employing the Likelihood paradigm, which uses likelihood ratios to measure the strength of evidence on a voxel-by-voxel basis. In this paper, we provide theoretical and empirical justification for a likelihood approach to the analysis of human brain imaging data. In addition, we present extensive simulations that show the likelihood approach is viable, leading to ‘cleaner’ looking brain maps and operationally superiority (lower average error rate). Finally, we include a case study on cognitive control related activation in the prefrontal cortex of the human brain. PMID:26272730

  6. The characteristic and changes of the event-related potentials (ERP) and brain topographic maps before and after treatment with rTMS in subjective tinnitus patients.

    PubMed

    Yang, Haidi; Xiong, Hao; Yu, Rongjun; Wang, Changming; Zheng, Yiqing; Zhang, Xueyuan

    2013-01-01

    To compare the event-related potentials (ERPs) and brain topographic maps characteristic and change in normal controls and subjective tinnitus patients before and after repetitive transcranial magnetic stimulation (rTMS) treatment. The ERPs and brain topographic maps elicited by target stimulus were compared before and after 1-week treatment with rTMS in 20 subjective tinnitus patients and 16 healthy controls. Before rTMS, target stimulus elicited a larger N1 component than the standard stimuli (repeating sounds)in control group but not in tinnitus patients. Instead, the tinnitus group pre-treatment exhibited larger amplitude of N1 in response to standard stimuli than to deviant stimuli. Furthermore tinnitus patients had smaller mismatch negativity (MMN) and late discriminative negativity (LDN)component at Fz compared with the control group. After rTMS treatment, tinnitus patients showed increased N1 response to deviant stimuli and larger MMN and LDN compared with pre-treatment. The topographic maps for the tinnitus group before rTMS -treatment demonstrated global asymmetry between the left and right cerebral hemispheres with more negative activities in left side and more positive activities in right side. In contrast, the brain topographic maps for patients after rTMS-treatment and controls seem roughly symmetrical. The ERP amplitudes and brain topographic maps in post-treatment patient group showed no significant difference with those in controls. The characterical changes in ERP and brain topographic maps in tinnitus patients maybe related with the electrophysiological mechanism of tinnitus induction and development. It can be used as an objective biomarker for the evaluation of auditory central in subjective tinnitus patients. These findings support the notion that rTMS treatment in tinnitus patients may exert a beneficial effect.

  7. Genome-Scale Reconstruction of the Human Astrocyte Metabolic Network

    PubMed Central

    Martín-Jiménez, Cynthia A.; Salazar-Barreto, Diego; Barreto, George E.; González, Janneth

    2017-01-01

    Astrocytes are the most abundant cells of the central nervous system; they have a predominant role in maintaining brain metabolism. In this sense, abnormal metabolic states have been found in different neuropathological diseases. Determination of metabolic states of astrocytes is difficult to model using current experimental approaches given the high number of reactions and metabolites present. Thus, genome-scale metabolic networks derived from transcriptomic data can be used as a framework to elucidate how astrocytes modulate human brain metabolic states during normal conditions and in neurodegenerative diseases. We performed a Genome-Scale Reconstruction of the Human Astrocyte Metabolic Network with the purpose of elucidating a significant portion of the metabolic map of the astrocyte. This is the first global high-quality, manually curated metabolic reconstruction network of a human astrocyte. It includes 5,007 metabolites and 5,659 reactions distributed among 8 cell compartments, (extracellular, cytoplasm, mitochondria, endoplasmic reticle, Golgi apparatus, lysosome, peroxisome and nucleus). Using the reconstructed network, the metabolic capabilities of human astrocytes were calculated and compared both in normal and ischemic conditions. We identified reactions activated in these two states, which can be useful for understanding the astrocytic pathways that are affected during brain disease. Additionally, we also showed that the obtained flux distributions in the model, are in accordance with literature-based findings. Up to date, this is the most complete representation of the human astrocyte in terms of inclusion of genes, proteins, reactions and metabolic pathways, being a useful guide for in-silico analysis of several metabolic behaviors of the astrocyte during normal and pathologic states. PMID:28243200

  8. Brain Activation during Addition and Subtraction Tasks In-Noise and In-Quiet

    PubMed Central

    Abd Hamid, Aini Ismafairus; Yusoff, Ahmad Nazlim; Mukari, Siti Zamratol-Mai Sarah; Mohamad, Mazlyfarina

    2011-01-01

    Background: In spite of extensive research conducted to study how human brain works, little is known about a special function of the brain that stores and manipulates information—the working memory—and how noise influences this special ability. In this study, Functional magnetic resonance imaging (fMRI) was used to investigate brain responses to arithmetic problems solved in noisy and quiet backgrounds. Methods: Eighteen healthy young males performed simple arithmetic operations of addition and subtraction with in-quiet and in-noise backgrounds. The MATLAB-based Statistical Parametric Mapping (SPM8) was implemented on the fMRI datasets to generate and analyse the activated brain regions. Results: Group results showed that addition and subtraction operations evoked extended activation in the left inferior parietal lobe, left precentral gyrus, left superior parietal lobe, left supramarginal gyrus, and left middle temporal gyrus. This supported the hypothesis that the human brain relatively activates its left hemisphere more compared with the right hemisphere when solving arithmetic problems. The insula, middle cingulate cortex, and middle frontal gyrus, however, showed more extended right hemispheric activation, potentially due to the involvement of attention, executive processes, and working memory. For addition operations, there was extensive left hemispheric activation in the superior temporal gyrus, inferior frontal gyrus, and thalamus. In contrast, subtraction tasks evoked a greater activation of similar brain structures in the right hemisphere. For both addition and subtraction operations, the total number of activated voxels was higher for in-noise than in-quiet conditions. Conclusion: These findings suggest that when arithmetic operations were delivered auditorily, the auditory, attention, and working memory functions were required to accomplish the executive processing of the mathematical calculation. The respective brain activation patterns appear to be modulated by the noisy background condition. PMID:22135581

  9. The peripheral retinal 'map'.

    PubMed Central

    Williams, D. H.

    1975-01-01

    The condition of the periphery of the retinal field of the human eye is of considerable significance, it is suggested, to those participating in various sporting activities. Its boundaries shrink and expand depending upon the physiological conditions imposed both upon the eye and upon the organism as a whole. Consequently its message to the brain may be impaired under stress with resulting danger owing to delayed response. Images Fig. 3 Fig. 4 Fig. 5 PMID:1148574

  10. Predictive Models of Human Visual Processes in Aerosystems.

    DTIC Science & Technology

    1979-11-01

    Physiology, 190:139-154. Wiesel, T. N. and D. H. Hubel, 1966. Spatial and chromatic interactions in the lateral geniculate body of the rhesus monkey...receiving a disproportionate share as reflected in the magnification factor in the retinotopic map of the dorsal lateral geniculate (Malpeli and Baker...optic chiasm before reaching its targets in the dorsal region of the lateral geniculate of the thalmus and the superior colliculus in the brain stem

  11. Mechanisms in Chronic Multisymptom Illnesses

    DTIC Science & Technology

    2008-10-01

    Craig AD, Chen K, Bandy D, Reiman EM. Thermosensory activation of insular cortex. Nat Neurosci 2000;3:184–90. 8. Singer T , Seymour B, O’Doherty J...to the Human Brain Mapping conference, June 2009. (See Appendix) S.J. Peltier, M.C Hsu, R.C. Welsh, R Bhavsar, R.E. Harris, D.J. Clauw, L. Symonds...College of Rheumatology, 2007. (See Appendix) Williams, DA, Patel, R ., Skalski, L., Chriscinske, SJ, Rubens, M., Lapedis, J., Harris, RE

  12. Sister grouping of chimpanzees and humans as revealed by genome-wide phylogenetic analysis of brain gene expression profiles

    PubMed Central

    Uddin, Monica; Wildman, Derek E.; Liu, Guozhen; Xu, Wenbo; Johnson, Robert M.; Hof, Patrick R.; Kapatos, Gregory; Grossman, Lawrence I.; Goodman, Morris

    2004-01-01

    Gene expression profiles from the anterior cingulate cortex (ACC) of human, chimpanzee, gorilla, and macaque samples provide clues about genetic regulatory changes in human and other catarrhine primate brains. The ACC, a cerebral neocortical region, has human-specific histological features. Physiologically, an individual's ACC displays increased activity during that individual's performance of cognitive tasks. Of ≈45,000 probe sets on microarray chips representing transcripts of all or most human genes, ≈16,000 were commonly detected in human ACC samples and comparable numbers, 14,000–15,000, in gorilla and chimpanzee ACC samples. Phylogenetic results obtained from gene expression profiles contradict the traditional expectation that the non-human African apes (i.e., chimpanzee and gorilla) should be more like each other than either should be like humans. Instead, the chimpanzee ACC profiles are more like the human than like the gorilla; these profiles demonstrate that chimpanzees are the sister group of humans. Moreover, for those unambiguous expression changes mapping to important biological processes and molecular functions that statistically are significantly represented in the data, the chimpanzee clade shows at least as much apparent regulatory evolution as does the human clade. Among important changes in the ancestry of both humans and chimpanzees, but to a greater extent in humans, are the up-regulated expression profiles of aerobic energy metabolism genes and neuronal function-related genes, suggesting that increased neuronal activity required increased supplies of energy. PMID:14976249

  13. Non-invasive imaging of the levels and effects of glutathione on the redox status of mouse brain using electron paramagnetic resonance imaging.

    PubMed

    Emoto, Miho C; Matsuoka, Yuta; Yamada, Ken-Ichi; Sato-Akaba, Hideo; Fujii, Hirotada G

    2017-04-15

    Glutathione (GSH) is the most abundant non-protein thiol that buffers reactive oxygen species in the brain. GSH does not reduce nitroxides directly, but in the presence of ascorbates, addition of GSH increases ascorbate-induced reduction of nitroxides. In this study, we used electron paramagnetic resonance (EPR) imaging and the nitroxide imaging probe, 3-methoxycarbonyl-2,2,5,5-tetramethyl-piperidine-1-oxyl (MCP), to non-invasively obtain spatially resolved redox data from mouse brains depleted of GSH with diethyl maleate compared to control. Based on the pharmacokinetics of the reduction reaction of MCP in the mouse heads, the pixel-based rate constant of its reduction reaction was calculated as an index of the redox status in vivo and mapped as a "redox map". The obtained redox maps from control and GSH-depleted mouse brains showed a clear change in the brain redox status, which was due to the decreased levels of GSH in brains as measured by a biochemical assay. We observed a linear relationship between the reduction rate constant of MCP and the level of GSH for both control and GSH-depleted mouse brains. Using this relationship, the GSH level in the brain can be estimated from the redox map obtained with EPR imaging. Copyright © 2017 Elsevier Inc. All rights reserved.

  14. Chemical mapping of anxiety in the brain of healthy humans: an in vivo 1H-MRS study on the effects of sex, age, and brain region.

    PubMed

    Grachev, I D; Apkarian, A V

    2000-12-01

    We recently presented results in an in vivo study of human brain chemistry in 'physiologic' anxiety, i.e., the anxiety of normal everyday life. Normal subjects with high anxiety demonstrated increased concentration of chemicals in orbital frontal cortex (OFC) as compared to lower anxiety. In a separate study of aging we demonstrated a decrease of total chemical concentration in OFC of middle-aged subjects, as compared with younger age. This brain region also showed gender dependence; men demonstrating decreased chemical concentration compared to women. We hypothesized that these sex- and age-dependent differences in OFC chemistry changes are a result of anxiety effects on this brain region. In the present study we examined these sex- and age-differential regional brain chemistry changes (as identified by localized in vivo proton magnetic resonance spectroscopy [1H-MRS]) in relation to the state-trait-anxiety (as measured by the State-Trait Anxiety Inventory) in 35 healthy subjects. The concentrations for all nine chemicals of 1H-MRS spectra were measured relative to creatine across multiple brain regions, including OFC in the left hemisphere. Analysis of variance showed anxiety-specific effects on chemical concentration changes in OFC, which were different for both sexes and age groups. Male subjects showed larger effect of anxiety on OFC chemistry as compared to females when the same sex high-anxiety subjects were compared to lower anxiety. Similarly, middle-aged subjects showed larger effect of anxiety on OFC chemistry as compared to younger age when the same age subjects with high anxiety were compared to lower anxiety. Largest effect of anxiety on OFC chemistry was due to changes of N-Acetyl aspartate. The results indicate that the state-trait anxiety has sex- and age-differential patterns on OFC chemistry in healthy humans, providing new information about the neurobiological roots of anxiety.

  15. Monitoring and control of amygdala neurofeedback involves distributed information processing in the human brain.

    PubMed

    Paret, Christian; Zähringer, Jenny; Ruf, Matthias; Gerchen, Martin Fungisai; Mall, Stephanie; Hendler, Talma; Schmahl, Christian; Ende, Gabriele

    2018-03-30

    Brain-computer interfaces provide conscious access to neural activity by means of brain-derived feedback ("neurofeedback"). An individual's abilities to monitor and control feedback are two necessary processes for effective neurofeedback therapy, yet their underlying functional neuroanatomy is still being debated. In this study, healthy subjects received visual feedback from their amygdala response to negative pictures. Activation and functional connectivity were analyzed to disentangle the role of brain regions in different processes. Feedback monitoring was mapped to the thalamus, ventromedial prefrontal cortex (vmPFC), ventral striatum (VS), and rostral PFC. The VS responded to feedback corresponding to instructions while rPFC activity differentiated between conditions and predicted amygdala regulation. Control involved the lateral PFC, anterior cingulate, and insula. Monitoring and control activity overlapped in the VS and thalamus. Extending current neural models of neurofeedback, this study introduces monitoring and control of feedback as anatomically dissociated processes, and suggests their important role in voluntary neuromodulation. © 2018 Wiley Periodicals, Inc.

  16. Induction of brain tumor stem cell apoptosis by FTY720: a potential therapeutic agent for glioblastoma.

    PubMed

    Estrada-Bernal, Adriana; Palanichamy, Kamalakannan; Ray Chaudhury, Abhik; Van Brocklyn, James R

    2012-04-01

    FTY720 is a sphingosine analogue that down regulates expression of sphingosine-1-phosphate receptors and causes apoptosis of multiple tumor cell types, including glioma cells. This study examined the effect of FTY720 on brain tumor stem cells (BTSCs) derived from human glioblastoma (GBM) tissue. FTY720 treatment of BTSCs led to rapid inactivation of ERK MAP kinase, leading to upregulation of the BH3-only protein Bim and apoptosis. In combination with temozolomide (TMZ), the current standard chemotherapeutic agent for GBM, FTY720 synergistically induced BTSC apoptosis. FTY720 also slowed growth of intracranial xenograft tumors in nude mice and augmented the therapeutic effect of TMZ, leading to enhanced survival. Furthermore, the combination of FTY720 and TMZ decreased the invasiveness of BTSCs in mouse brains. FTY720 is known to cross the blood-brain barrier and recently received Food and Drug Administration approval for treatment of relapsing multiple sclerosis. Thus, FTY720 is an excellent potential therapeutic agent for treatment of GBM.

  17. A versatile clearing agent for multi-modal brain imaging

    PubMed Central

    Costantini, Irene; Ghobril, Jean-Pierre; Di Giovanna, Antonino Paolo; Mascaro, Anna Letizia Allegra; Silvestri, Ludovico; Müllenbroich, Marie Caroline; Onofri, Leonardo; Conti, Valerio; Vanzi, Francesco; Sacconi, Leonardo; Guerrini, Renzo; Markram, Henry; Iannello, Giulio; Pavone, Francesco Saverio

    2015-01-01

    Extensive mapping of neuronal connections in the central nervous system requires high-throughput µm-scale imaging of large volumes. In recent years, different approaches have been developed to overcome the limitations due to tissue light scattering. These methods are generally developed to improve the performance of a specific imaging modality, thus limiting comprehensive neuroanatomical exploration by multi-modal optical techniques. Here, we introduce a versatile brain clearing agent (2,2′-thiodiethanol; TDE) suitable for various applications and imaging techniques. TDE is cost-efficient, water-soluble and low-viscous and, more importantly, it preserves fluorescence, is compatible with immunostaining and does not cause deformations at sub-cellular level. We demonstrate the effectiveness of this method in different applications: in fixed samples by imaging a whole mouse hippocampus with serial two-photon tomography; in combination with CLARITY by reconstructing an entire mouse brain with light sheet microscopy and in translational research by imaging immunostained human dysplastic brain tissue. PMID:25950610

  18. Mapping Resting-State Brain Networks in Conscious Animals

    PubMed Central

    Zhang, Nanyin; Rane, Pallavi; Huang, Wei; Liang, Zhifeng; Kennedy, David; Frazier, Jean A.; King, Jean

    2010-01-01

    In the present study we mapped brain functional connectivity in the conscious rat at the “resting state” based on intrinsic blood-oxygenation-level dependent (BOLD) fluctuations. The conscious condition eliminated potential confounding effects of anesthetic agents on the connectivity between brain regions. Indeed, using correlational analysis we identified multiple cortical and subcortical regions that demonstrated temporally synchronous variation with anatomically well-defined regions that are crucial to cognitive and emotional information processing including the prefrontal cortex (PFC), thalamus and retrosplenial cortex. The functional connectivity maps created were stringently validated by controlling for false positive detection of correlation, the physiologic basis of the signal source, as well as quantitatively evaluating the reproducibility of maps. Taken together, the present study has demonstrated the feasibility of assessing functional connectivity in conscious animals using fMRI and thus provided a convenient and non-invasive tool to systematically investigate the connectional architecture of selected brain networks in multiple animal models. PMID:20382183

  19. From a meso- to micro-scale connectome: array tomography and mGRASP

    PubMed Central

    Rah, Jong-Cheol; Feng, Linqing; Druckmann, Shaul; Lee, Hojin; Kim, Jinhyun

    2015-01-01

    Mapping mammalian synaptic connectivity has long been an important goal of neuroscience because knowing how neurons and brain areas are connected underpins an understanding of brain function. Meeting this goal requires advanced techniques with single synapse resolution and large-scale capacity, especially at multiple scales tethering the meso- and micro-scale connectome. Among several advanced LM-based connectome technologies, Array Tomography (AT) and mammalian GFP-Reconstitution Across Synaptic Partners (mGRASP) can provide relatively high-throughput mapping synaptic connectivity at multiple scales. AT- and mGRASP-assisted circuit mapping (ATing and mGRASPing), combined with techniques such as retrograde virus, brain clearing techniques, and activity indicators will help unlock the secrets of complex neural circuits. Here, we discuss these useful new tools to enable mapping of brain circuits at multiple scales, some functional implications of spatial synaptic distribution, and future challenges and directions of these endeavors. PMID:26089781

  20. A conserved pattern of differential expansion of cortical areas in simian primates.

    PubMed

    Chaplin, Tristan A; Yu, Hsin-Hao; Soares, Juliana G M; Gattass, Ricardo; Rosa, Marcello G P

    2013-09-18

    The layout of areas in the cerebral cortex of different primates is quite similar, despite significant variations in brain size. However, it is clear that larger brains are not simply scaled up versions of smaller brains: some regions of the cortex are disproportionately large in larger species. It is currently debated whether these expanded areas arise through natural selection pressures for increased cognitive capacity or as a result of the application of a common developmental sequence on different scales. Here, we used computational methods to map and quantify the expansion of the cortex in simian primates of different sizes to investigate whether there is any common pattern of cortical expansion. Surface models of the marmoset, capuchin, and macaque monkey cortex were registered using the software package CARET and the spherical landmark vector difference algorithm. The registration was constrained by the location of identified homologous cortical areas. When comparing marmosets with both capuchins and macaques, we found a high degree of expansion in the temporal parietal junction, the ventrolateral prefrontal cortex, and the dorsal anterior cingulate cortex, all of which are high-level association areas typically involved in complex cognitive and behavioral functions. These expanded maps correlated well with previously published macaque to human registrations, suggesting that there is a general pattern of primate cortical scaling.

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